Study Protocol
Title: Equine Assisted Activities /Therapy
(EAA/T) for Veterans with Post Traumatic
Stress Disorder (PTSD)
Protocol No.: WP-EP-Equine- 001
Revision: 01
Date of Protocol Version: March 2015
Sponsor: TBD (protocol applied for sponsorship).
Principal Investigators: Prof. Arieh Shalev M.D, Anita Shkedi MSc,
Co-investigators: Prof. Giora Pillar M.D. Prof. Amir Lerman M.D, Steven Lamm M.D., Koby
Sheffy PhD, MaryJo Beckman M.Sc.,
1
Equine Assisted Activities /Therapy (EAA/T) for Veterans with Post Traumatic Stress Disorder
(PTSD)
CLINICAL STUDY PROTOCOL SYNOPSIS
Sponsor:
To be decided
Title:
Equine Assisted Activities /Therapy (EAA/T) for Veterans with Post
Traumatic Stress Disorder (PTSD)
Equine Assisted Equine Assisted Activities /Therapy (EAA/T) is a human–horse
experience that provides and facilitates a treatment modality for people
Activities/
Therapy EAA/T: from all backgrounds in a variety of ways that encourages physical,
cognitive and behavioral improvement. EAA/T results in increased
strength and flexibility, improved motor skills, promotion of speech and
cognitive reasoning, as well as building relationships and social skills.
EAA/T is a global term that embraces TR (Therapeutic horseback
Riding), therapeutic carriage driving, interactive vaulting, (similar to
gymnastics on horseback), equine-facilitated learning, educational
health activities to improve intellectual ability and hippo-therapy. The
therapeutic activities are carried out either on the ground or on top of
the horse, in the arena, or around the stable.
Study Design:
Prospective Study
Sample Size:
A total of 200 subjects
Clinical Site:


Israel National Therapeutic Riding Association (INTRA), Bnei Zion
Caisson Platoon Equine Assisted Program, Washington DC
Study Objectives

Study Endpoints
Primary Endpoints:
 Cognitive and psychological parameters using validated
questionnaires (the Post-Traumatic Cognition Inventory PTCI)
 Sleep efficiency (ratio of sleep time to time in bed).
 Sexual Health Inventory for Men (SHIM) score using International
Index of Erectile function (IIEF-5) Questionnaire for Men’s sexual
function
 Endothelial function assessment as a marker of arterial health as
The objective of this study is to show that EAA/T is an
effective treatment method for veterans with chronic Post
Traumatic Stress Disorder (PTSD) applying objective
quantitative measurements
2
measured by EndoPATTM
Secondary endpoints:
 Sleep latency – time from lights off to falling asleep
 Total sleep time
 REM sleep stage percentage defined as the ratio between total
REM sleep-time to total sleep time
 REM latency – time form lights off to entering first REM stage
 Deep sleep percentage defined as total deep sleep time to total sleep
time
 Number of arousals from sleep
 Count of subject’s reported nights with nightmares
 Sympathetic response to mental stress test, as measured by PAT
signal.
Subject
population:
Adult male veterans suffering from chronic PTSD
Inclusion
Criteria:



Exclusion
Criteria:
Methods:



Age between 18-70
Subject is a male veteran suffering from PTSD
Subject is able to read, understand and sign the informed consent
form
Subject is willing to comply with the schedule of the study follow-up
Permanent pacemaker: a trial pacing or VVI without sinus rhythm
Use of one of the following medications: alpha blockers, short acting
nitrates (less than 3 hours before the study)
Subjects will come for 30 weekly sessions. Subject assessment will be
performed three times: at baseline, after 15 sessions and at study
termination-after 30 sessions
Assessment will include:
1. “PTSD Checklist Questionnaire”
2. In home sleep diagnostic test with the Watch-PAT200
3. Epworth sleep questionnaire-to assess day time sleepiness
4. Report of nightmares
5. Sympathetic response to mental stress manifested by PAT
signal using EndoPAT
6. Endothelium Function test-as measured by the EndoPAT
7. Sexual function assessment using IIEF -5 Questionnaire
3
Approvals:
4
Table of Contents
1
INTRODUCTION ........................................................................................................................... 7
1.1
1.2
1.3
2
BACKGROUND ......................................................................................................................... 7
RATIONALE ............................................................................................................................. 9
ABBREVIATIONS .................................................................................................................... 10
METHODS:
2.1
2.2
2.3
2.4
2.5
2.6
2.7
2.8
2.9
....................................................................................................................... 10
ASSESSMENT OF PTSD .......................................................................................................... 10
EQUINE ASSISTED ACTIVITIES/ THERAPY (EAA/T) .............................................................. 10
PAT SIGNAL .......................................................................................................................... 11
SLEEP TEST ............................................................................................................................ 11
EPWORTH SLEEP QUESTIONNAIRE.......................................................................................... 11
REPORT OF NIGHTMARES ....................................................................................................... 12
ENDOTHELIAL FUNCTION TEST ............................................................................................. 12
SEXUAL FUNCTION ASSESSMENT ........................................................................................... 12
MENTAL STRESS TEST........................................................................................................... 12
3
STUDY OBJECTIVES ................................................................................................................. 13
4
STUDY ENDPOINTS ................................................................................................................... 13
4.1
4.2
PRIMARY ENDPOINTS:............................................................................................................ 13
SECONDARY ENDPOINTS:....................................................................................................... 13
5
INVESTIGATOR(S) AND OTHER STUDY PARTICIPANTS ............................................... 14
6
STUDY POPULATION AND SUBJECT SELECTION ........................................................... 14
6.1
6.2
7
STUDY POPULATION .............................................................................................................. 14
SUBJECT SELECTION.............................................................................................................. 14
STUDY DESIGN AND METHODS ............................................................................................ 14
7.1
7.2
7.3
7.4
7.5
7.6
OVERALL DESCRIPTION......................................................................................................... 14
VISIT 1- (BASE LINE VISIT) ..................................................................................................... 15
VISITS 2-14 ........................................................................................................................... 15
VISIT 15 – INTERMEDIATE ASSESSMENT: ............................................................................... 15
VISITS 16-29 ......................................................................................................................... 16
VISIT 30- STUDY END ............................................................................................................ 16
8
SCHEDULE OF EVENTS ........................................................................................................... 17
9
RISKS AND BENEFITS: ............................................................................................................. 17
9.1
9.2
RISKS .................................................................................................................................... 17
BENEFITS ............................................................................................................................... 18
10 SUBJECT STUDY DISCONTINUATION AND REPLACEMENT........................................ 18
10.1
SUBJECT DISCONTINUATION ................................................................................................. 18
11 DEVIATIONS FROM PROTOCOL ........................................................................................... 18
12 INFORMED CONSENT .............................................................................................................. 19
13 SAMPLE SIZE AND STUDY DURATION ............................................................................... 19
14 STUDY MONITORING AND DATA COLLECTION: ............................................................ 19
14.1
14.2
14.3
STUDY ADMINISTRATION: ..................................................................................................... 19
STUDY MONITORING ............................................................................................................. 20
ETHICAL CONSIDERATIONS ................................................................................................... 20
5
14.4
14.5
14.6
DATA COLLECTION ............................................................................................................... 20
DATA MANAGEMENT ............................................................................................................ 21
ADVERSE EVENT REPORTING ................................................................................................ 21
15 PROTOCOL MODIFICATIONS ................................................................................................ 21
16 SUBJECT CONFIDENTIALITY ................................................................................................ 21
REFFERENCES
......................................................................................................................... 20
APPENDIX 1: DSM CLASSIFICATION OF PTSD ........................................................................ 25
6
1
1.1
INTRODUCTION
Background
Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder associated with intense
psychological and emotional distress following a traumatic event. PTSD is characterized
by re-experiencing the trauma suffered, avoidance of trauma-related stimuli, restricted
affect, hyper-vigilance, and social isolation1. PTSD has also been found to be linked to
considerable physical comorbidity, unhealthy lifestyles, and increased all-cause mortality
in addition to increased suicidal behaviours and attempts2; 3.
Overall PTSD prevalence in US Veterans Affairs (VA) primary care clinics was reported
as 11.5% in 20054. The prevalence of PTSD in Israeli veterans is unclear because of
conflicting reports. However, following recent operations, such as Protective Edge (Tzuk
Eitan) in the summer of 2014, several reports of suicide and PTSD among soldiers have
raised the awareness of PTSD in the Israeli Defence Forces (IDF) and in Israeli society5-8.
The Diagnostic and Statistical Manual of Mental Disorders (DSM), published in 2013,
inserted modifications to the previous DSM-IV assessment guidelines. Compared to
DSM-IV, the diagnostic criteria for DSM-5 draws a clearer line when detailing what
constitutes a traumatic event9. Since its implementation in 2013, DSM-5 has drawn
criticism with 30% of previously diagnosed patients no longer fitting this group
according to one study. However, the general percentage of diagnosed veterans remains
the same, as new patients, not fitting DSM-IV PTSD criteria, now fit into PTSD
diagnosis10.
DSM-5 puts more emphasis on the behavioural symptoms that accompany PTSD and
removed the following specification that appears in DSM-IV: “The person’s response
involved intense fear, helplessness, or horror”, no longer requiring response criteria11.
DSM-5 proposes four distinct diagnostic clusters instead of three clusters used in DSMIV. They are described as re-experiencing, avoidance, negative cognitions and mood, and
arousal.
DSM-5 requires that a disturbance continue for more than a month, eliminating the
distinction between acute and chronic phases of PTSD.
Sleep disorders, nightmares and hyper-arousal are incorporated within the definition of
PTSD of both DSM-5 and DSM-IV, but are not based on objective measurements, mostly
7
due to unavailability of methods that can be applied to test these very vulnerable patients.
The most frequent self-reported complaints are: difficulties falling asleep, frequent
awakenings from sleep (with further difficulties falling back to sleep), shorter sleep
duration, restless sleep, daytime fatigue, especially nightmares and anxiety dreams12.
Polysomnography (PSG) in-lab sleep tests of PTSD subjects have conflicting outcomes,
with a dissonance between subjective reported sleep quality and in-lab sleep test results.
Ambulatory sleep studies using acticraphy to monitor sleep quality, also have not been
consistent with self-reported sleep disorders13.
Several studies have reported abnormalities in (Rapid Eye Movement) REM sleep in
PSTD subjects. The chronic hyper-arousal state in these patients may explain the REM
abnormalities of lower or higher REM appearances rate as compared to the non-PTSD
population. Sleep architecture in PTSD has also shown various patterns. This may be
partly due to comorbidities frequently found in this group, such as depression, which also
has an effect on sleep architecture. Sleep studies in this population also report an
increased rate of limb movements and apnoea events12.
There is increasing evidence of the impact of PTSD on cardiovascular health. A metaanalysis of the prospective association of PTSD with incident Coronary Heart Disease
(CHD) and cardiac-specific mortality, found that PTSD is associated with a 27% increase
in risk for incident CHD or cardiac-specific mortality after adjustment for numerous
factors including depression14. There are several possible physiological factors linking
PTSD with increased CHD risk. PTSD is associated with prolonged reactivity of the
autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis, which,
controls reactions to stress and regulates many body processes and therefore, can
contribute to the development and progression of atherosclerosis and cardiovascular
system damage. Other physiological characteristics that can be evidence of autonomic
dysfunction in both PTSD and CHD development are decreased heart rate variability
(associated with increased mortality risk after MI), bar reflex dysfunction (associated
with carotid atherosclerosis and increased risk of incident CHD) and increased QT
variability on the electrocardiogram (a predictor of sudden cardiac death) 15.
Sexual dysfunction is found in a large number of returning combat veterans. It can result
in reduced quality of life, decreased sexual intimacy, and increased health-care
utilization. A retrospective cohort study of 405,275 male Iraq and Afghanistan veterans in
the USA VA healthcare system, demonstrated that PTSD increased the risk of sexual
dysfunction by more than threefold. Furthermore, psychiatric medications, often
prescribed to this population, appeared to significantly increase the risk of sexual
dysfunction. This study showed that among U.S. combat veterans, mental health
8
disorders, particularly PTSD, increased the risk of sexual dysfunction independent of the
use of psychiatric medications16.
Currently, there is no acceptable marker to predict or corroborate recovery in PTSD
patients. Mental stress induces significant activation of the autonomic nervous system
and may play a major role in many of PTSD symptoms17. Many PTSD patients continue
to suffer, despite treatment, and there is currently no efficient way to prevent the disorder
under its naturally occurring circumstances18.
A pilot study conducted by the Israel National Therapeutic Riding Association (INTRA)
in 2010, with 10 Israeli Defense Forces (IDF) veteran subjects with chronic PTSD,
demonstrated encouraging preliminary therapeutic effect of EAA/T.
Utilizing
observations, questionnaires and interviews, the team at INTRA identified some
significant positive changes in subjects' quality of life parameters. The outcomes
indicated a significant decrease in nightmares, reduction of hyper-alertness, improved
communication skills, motivation and self-esteem, improvement in family relations,
reduction of depression and consumption of medications, and in some cases ability to
return to work26. This pilot study indicated that EAA/T can address most symptoms of
PTSD, and should be considered as a useful intervention for both prevention and
reduction of symptoms. It revealed that EAA/T can both prevent and address problems
of poor interpersonal and intergenerational relationships, and when problems have
already occurred, their negative impact can be reduced.
EAA/T interventions are especially designed to assist all negative forms of emotional
behaviour. The success of EAA/T lies within the unique capabilities and characteristics
of the horse. To survive in the wild, the horse has been gifted with rapid response to any
predatory feeling, it can desensitise itself from that feeling faster than any other
animal. It also has an infallible memory and extraordinary perception, all of which helps
someone suffering from PTSD face their reality; rebuild trust and personal confidence
and communication, as well as reset boundaries and limits.
The instances of veterans with PTSD have reached crisis proportions throughout the world. We
believe this study will impact medical management programs for PTSD worldwide.
1.2
Rationale
PTSD is known to have major effect on the autonomic nervous system, more specifically, its’
sympathetic arm. Current limited evidence suggests that EAA/T might be a successful
holistic therapeutic technique for treating the main PTSD characteristics and supports the
hypothesis that PTSD sufferers could benefit from it19. EAA/T may specifically affect
subject’s nonverbal, arousal and autonomic functioning. To validate and further develop
9
these preliminary results, we propose to conduct a well-controlled study with the addition
of objective, quantitative quality measurements for assessing EAA/T technique along
with subjective questionnaires.
These objective parameters will evaluate the cardiovascular system, assess sleep
disorders and include a physiological measure of sympathetic activation for predicting
treatment success.
1.3
Abbreviations

















2
2.1
AHI - Apnea-Hypopnea Index
ECRF – Electronic Case Report Form
EAA/T - Equine Assisted Activities /Therapy
INTRA – Israel National Therapeutic Riding Association
OSA - Obstructive Sleep Apnea
PAT - Peripheral Arterial Tonometry
PSG – Polysomnography
PTSD – Post Traumatic Stress Disorder
OSA – Obstructive Sleep Apnea
RDI - Respiratory Disturbance Index
AHI – Apnea Hypopnea Index
REM – Rapid Eye Movement
SBP – Snoring Body Position
SDB - Sleep Disorder Breathing
SOP - Standard Operating Procedure
WP200 – WatchPAT200
WP200U – WatchPAT200 Unified
Methods:
Assessment of PTSD
PTSD assessment will be performed using the DSM-5 criteria, using DSM V version of
the PCL, “PTSD Checklist Questionnaire” (Keane, Weathers et al, 1993) for evaluating
subjects’ PTSD level at baseline, mid study- (visit/week 15) and final visit, at 30 weeks.
Trauma related cognitions would be assessed using the Post-Traumatic Cognition
Inventory27
2.2
Equine Assisted Activities/ Therapy (EAA/T)
Equine Assisted Activities /Therapy (EAA/T) is a human–horse experience that provides
and facilitates a treatment modality for people from all backgrounds in a variety of ways
that encourages physical, cognitive and behavioural improvement, including increased
strength and flexibility, improved motor skills, promotion of speech and cognitive
10
reasoning, as well as building relationships and social skills. EAA/T is a global term that
embraces TR (Therapeutic horseback Riding), therapeutic carriage driving; interactive
vaulting, that is similar to gymnastics on horseback; equine-facilitated learning,
educational health activities to improve intellectual ability, and hippo-therapy. The
therapeutic activities are carried out either on the ground or on top of the horse, in the
arena, or in or around the stable.
2.3
PAT signal
The PAT signal is measured in the finger and it is an accurate and robust measure of the
pulsatile volume change of the digital vascular arterial bed. The vasomotion of the digital
arteries is regulated by two systems – the sympathetic branch of the autonomic nervous
system and the endothelial system. As such, it serves as a "window" to changes and
disorders associated with two systems
2.4
Sleep test
Attended in-lab sleep studies are the gold standard for assessing sleep disorders.
However, the high cost and the cumbersome logistics associated with including such a
test in this study make this option less feasible. Due to some inherent limitations
associated with the proposed subject population such as: sleeping in an unfamiliar
environment and being connected to numerous disturbing sensors, the study will include
an ambulatory home sleep study with the WatchPAT200 (WP200) or WatchPAT200U
(WP200U) as the diagnostic device.
The Watch-PATTM200 (WP200), and WatchPATTM200/U (WP200U), are FDA cleared
(K081982; K133859) patient-worn devices used at home for aiding in the diagnosis of
Obstructive Sleep Apnoea (OSA) based on Peripheral Arterial Tonometry (PAT) signal, a
non-invasive technology. The controller part of the device is worn on the wrist, and
records the vasomotor activity in the distal part of the finger by a finger-mounted
pneumo-optical plethysmographic probe. A pulse oximeter provides arterial blood
saturation information. An Actigraph, embedded in the wrist worn controller unit, records
wrist motion, used to determine periods of sleep. An off line PC program (the
WatchPAT) provides the Respiratory Disturbance Index (RDI), the Apnoea Hypopnea
Index (AHI) and identifies sleep stages (REM sleep, light sleep, deep sleep and Wake).
An optional combined Snoring and Body Position (SBP) sensor can be attached to the
patient’s sternal notch.
2.5
Epworth sleep questionnaire
The Epworth Sleep Questionnaire (ESS) is a self-administered questionnaire with 8
questions. The total ESS provides a measure of a person’s general level of daytime
sleepiness, or their average sleep propensity in daily life. The ESS asks people to rate, on
11
a 4-point scale (0 – 3), their usual chances of dozing off or falling asleep in 8 different
situations or activities that most people engage in as part of their daily lives, although not
necessarily every day. It does not ask people how often they doze off in each situation.
The total ESS score is the sum of 8 item-scores and can range between 0 and 24. The
higher the score, the higher the person’s level of daytime sleepiness.
2.6
Report of nightmares
Subjects will be asked to keep a daily sleep diary, which will include nightmares and selfassessed sleep quality, reported upon waking up.
2.7
Endothelial Function Test
Peripheral endothelial function will be assessed with EndoPATTM that has been described
previously in detail20,21. A blood pressure cuff is placed on one upper arm, while the
contralateral arm serves as a control. Peripheral arterial tonometry probes are placed on
one finger of each hand. After a 5-minute baseline measurement period, the blood
pressure cuff is inflated to a supra-systolic pressure for 5-minutes, and then abruptly
deflated, inducing reactive hyperaemia. RH-PAT data is automatically analysed by
dedicated computer hosted software. The RH-PAT index (RHI) is calculated as the ratio
of average amplitude of the PAT signal over a 1-minute time interval, starting 1.5
minutes after cuff deflation, divided by its average amplitude over a 2.5-minute time
period before cuff inflation (baseline) through a computer algorithm automatically
normalizing for baseline signal and indexed to the contralateral arm. The EndoScore
result is given by LnRHI which is a natural log transformation of the RH-PAT index
(RHI).
2.8
Sexual function assessment
A score generated by IIEF-5 25 questionnaire will perform assessment of sexual function
2.9
Mental Stress Test
A counting down autonomic stressor has been shown to affect cardio-vascular
performance and sympathetic control when assessed by changes in Peripheral Arterial
Tone (PAT) signal22,23 and a more robust method based on a computer task induced stress
was later presented 24 .
The study subjects will be assessed at 3 time points: at baseline, i.e., before starting
therapy, after completing 15 sessions (15 weeks) and right after terminating the
treatment.
12
3

STUDY OBJECTIVES
To show that EAA/T is an effective treatment method for veterans with chronic Post
Traumatic Stress Disorder (PTSD).
To evaluate EAA/T success via objective quantitative measures: sleep study,
vascular health assessment, and mental stress test.

4
STUDY ENDPOINTS
We hypothesize that improvement will significantly alleviate the on-going distress and
disability from which these military veterans suffer in a number of ways. Following
EAA/T, there will be a significant improvement in the manifestation and symptoms of the
post-traumatic stress disorder among subjects, as well as in the areas of physical change
that include an improvement in posture, balance and co-ordination, body and spatial
awareness. There will also be changes in cognition, such as a healthier ability to learn
new skills that include horseback riding knowledge and horse care and management.
Socially and emotionally, the veteran will find it easier to connect with obvious
enjoyment to another living being while participating in the “farm” social activities. This
significant improvement in their quality of life at the “farm” will manifest in repair of
negative symptoms of depression, in their ability to regulate physical and emotional
expressions, and in their self-confidence. A change in the quality of life will result in a
feeling of self -worth, a renewed sense of timing and a reduction in the level of anger and
hyper arousal. These all-important transferable skills will make life much more
manageable and pleasant for the veteran in other environments.
4.1




4.2








Primary endpoints:
Cognitive and psychological parameters using validated questionnaires. (The Post
Traumatic Cognition Inventory PTCI).
Sleep efficiency (ratio of sleep time to time in bed).
SHIM score using IIEF-5 Questionnaire for Men’s sexual function
Endothelial function assessment as a marker of arterial health as measured by EndoPATTM
Secondary endpoints:
Sleep latency – time from lights off to falling asleep
Total sleep time
REM sleep stage percentage defined as the ratio between total REM sleep time to total sleep
time
REM latency – time from lights off to entering first REM stage
Deep sleep percentage defined as total deep sleep time to total sleep time
Number of arousals from sleep
Count by subject reported nights with nightmares
Sympathetic response to mental stress test, as measured by PAT signal
13
5
INVESTIGATOR (S) AND OTHER STUDY PARTICIPANTS
This is a multi-center study.
Appendix 1.)
(Detailed list of participating centers is included in
Information regarding key personnel involved in the conduct of the study in each site,
including contact details of participating investigators, sub-investigators, technical
personnel will be found in the study files of the sponsor and on site, if requested.
6
6.1
STUDY POPULATION AND SUBJECT SELECTION
Study Population
The study population will include 100 adult veterans suffering from chronic PTSD,
referred to the study through Israel National Therapeutic Riding Association, NICoE,
Fort Belvoir, and the Educational, Research and Treatment Facility Longmont, Colorado
6.2
Subject Selection
Inclusion Criteria




Age between 18-70
Subject is a veteran suffering from PTSD
Subjects is able to read, understand and sign the informed consent form
Subject is willing to comply with study follow-up schedule.
Exclusion Criteria

Permanent pacemaker: atrial pacing or VVI without sinus rhythm.

Use of one of the following medications: alpha blockers, short acting nitrates (less than 3
hours before the study)
7
7.1
STUDY DESIGN AND METHODS
Overall Description
The current study is a multi-site, prospective study, to determine the efficacy of EAA/T
method for veterans with chronic Post Traumatic Stress Disorder (PTSD).
100 adult veterans suffering from chronic PTSD, age 18-70, in Israel and the USA, will
be invited to participate in the study. Subjects will come for 30 weekly sessions at the
EAA/T center.
14
7.2
Visit 1- (base line visit)
After signing an informed consent form (ICF), subjects’ demographic and medical
information will be acquired and will be recorded on the appropriate case report forms
(CRF or ECRF).
Subjects will undergo the baseline assessment:
1. DSM V version of the PCL, “PTSD Checklist Questionnaire” (Keane, Weathers et
al, 1993)
2. IIEF-5 questionnaire for the assessment of men’s sexual dysfunction
3. In home sleep diagnostic test with the Watch-PAT200
4. Epworth sleep questionnaire-to assess day time sleepiness
5. Report of nightmares
6. Mental stress test – while measuring Sympathetic activation with the EndoPAT
7. Endothelia Function test-as measured by the EndoPAT
8. Sexual function assessment with sexual function Questionnaire
9. Blood test
Following baseline assessments subjects will undergo EAA/T session.
7.3
Visits 2-14
Subject will submit diaries and will:
1. Report nightmares
2. Participate in EAA/T Therapeutic sessions
After initial assessment, the subject will participate in 1 hour the EAA/T sessions.
Visit 15 – Intermediate Assessment:
Subjects will:
1.
2.
3.
4.
5.
6.
7.
8.
9.
DSM V version of the PCL, “PTSD Checklist Questionnaire”
In home sleep diagnostic test with the Watch-PAT200
Epworth sleep questionnaire-to assess day time sleepiness
Report of nightmares
Mental stress test – while measuring Sympathetic Activation with the EndoPAT
Endothelial Function test-as measured by the EndoPAT
Sexual function assessment with Sexual Function Questionnaire
Blood test
EAA/T session
Following the above intermediate assessments, the subject will undergo the session of EAA/T per
protocol.
15
7.4
Visits 16-29
Same protocol as visits 2-14.
7.5
Visit 30- Study End
Same as visit 15 (baseline visit), in addition to study termination forms.
16
8
SCHEDULE OF EVENTS
Visit 1
Visits 2-14
Week 2-14
Visits 15
Week 15
Visits 15-29
Week 15-29
Visit 30
Week 30
ICF
Inclusion
Exclusion
Demographics
Medical History
Medications
+
+
+
+
+
+
+
PTSD Checklist
WP200 Sleep Test
EndoPAT
Epworth
Questionnaire
Nightmares
Report
Mental Stress
Sexual Function
Adverse Events
Blood Test
Study
Termination
EAA/T
+
+
+
+
+
+
+
+
+
+
+
+
9
9.1
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
RISKS AND BENEFITS:
Risks
EAA/T has proved to be a low risk horseback riding activity as the therapy generally takes place
in a controlled environment. Contra-indications to EAA/T and especially horseback riding
include, brittle bones/ osteoporosis, acute inflammatory conditions, uncontrolled epilepsy, allergy
to the horse and grass. Conditions that indicate an increased risk, are dizziness and
drowsiness, hypertension, peripheral vascular disease especially where there are skin lesions, lack
of head and neck control, bruising and bleeding and excessive pain. The WP200 and the
EndoPAT are low-risk devices, thus the occurrence of adverse reactions is unlikely and the
probability of hazards due to malfunction of the device is very low. Nevertheless, any adverse
reactions reported by subjects or noted by study personnel will be recorded.
17
9.2
Benefits
Following EAA/T, there may be a significant improvement in the manifestation and
symptoms of PTSD among the subjects that may include some or all of the following:
•
•
•
•
•
•
•
•
Reduced emotional numbness
Ability to connect emotionally and socially to other living beings
Finding a voice to express thoughts, wishes, needs
Improved self-image and body awareness
Belief in abilities
Experiencing moments of joy pride and peace that transfers into lives beyond EAA/T
sessions
Lowered anxiety
Lowered hyper-arousal level
Representing the above, subjects may witness improvement in sleep as well as
reduction of difficulties such as nightmares, anxiety at early morning and before sleep.
10 SUBJECT STUDY DISCONTINUATION and REPLACEMENT
10.1 Subject Discontinuation
A subject should be removed from the study whenever considered necessary for his/her welfare
or whenever he/she requests, at any stage of the study. Non-compliance with the protocol or the
occurrence of a significant adverse event may necessitate discontinuing a subject.
If the subject studied discontinues with the study, the reason must be entered into the ECRF and
signed by the principal investigator. In the case of any questionable situation, the study monitor
or sponsor personnel should be consulted.
Adverse events must be followed to resolution.
11 DEVIATIONS FROM PROTOCOL
When circumstances arise which suggest that a deviation from this protocol should be considered,
the investigator or other physician in attendance must contact the study monitor as soon as
possible prior to implementation. Any deviation from protocol will pertain only to the individual
subject involved. The CRF will describe the circumstances and identify the pertinent protocol
procedure.
Modification of the protocol that may become necessary during the course of this study, other
than to protect subjects from an immediate hazard is subject to prior discussion between the
clinical investigator and the study monitor.
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12 INFORMED CONSENT
The investigator is responsible for obtaining written informed consent from subjects prior to
study entry. The subjects will be asked to read the informed consent form and to sign the form to
indicate their willingness and consent to participate in the study.
The investigator (or his designated representative) will explain the research and nature of the
study to the subjects along with known or foreseeable benefits, risks and discomforts that subjects
may experience. The subjects must understand that throughout the study their participation
remains voluntary and protected by the Declaration of Helsinki. The informed consent (approved
by the sponsor and the IRB Committee) must be signed and dated by the subject and the
investigator.
Subjects may withdraw their consent to participate in the study at any time without prejudice. The
investigator may withdraw a subject if, in his clinical judgment, it is in the best interest of the
subject or if the subject cannot comply with the protocol. Attempt should be made to complete
any examinations and the sponsor must be notified of all withdrawals.
Should a protocol amendment be made, the subject's consent form may be revised to reflect the
changes of the protocol. It is the responsibility of the investigator to ensure that an amended
consent is approved or reviewed by the ethical committee, and that all subjects sign it
subsequently entered in the study and those currently in the study, if affected by the amendment.
13 SAMPLE SIZE AND STUDY DURATION
From our experience, dropout in similar studies can be as high as 50%. However, with special
attention and resources invested to support subject’s transportation to the sessions and increased
comfort while staying in the premises of the EAA/T center, this can probably be reduced to 25% 30%. Thus, in order to have 80 subjects complete the study (PP – Per Protocol) we shall need to
enroll 120 subjects (ITT – Intent to Treat). Additionally the project will be on-going for two
years, as we will need to spread the intake in order to cope with the number of subjects. End
intervention data readings shall be taken from subjects regardless of not completing the 30
sessions. Intermittent assessment of treatment will be performed after 15 sessions.
14 STUDY MONITORING AND DATA COLLECTION:
14.1 Study Administration:
The site personnel will be trained at the study implementation to conduct the study in accordance
with the applicable procedures for conducting the clinical investigation.
A study handbook will be prepared for the site, including all necessary paperwork required to be
maintained at the site. Paperwork includes IRB approval, study/investigator agreement, study
protocol, and instructions for the site personnel.
19
A site coordinator will be assigned to coordinate activities required at the site and to liaison with
the study monitor. The site coordinator will manage subject recruitment, enrollment and ensure
that CRFs are accurately completed and submitted in a timely manner to the data entry center.
14.2 Study Monitoring
The site will be monitored by INTRA and Itamar Medical representatives to ensure that
the investigators are conducting the clinical trials in compliance with the protocol, and
applicable requirements and regulations. The study monitor will assess the quality of the
clinical data collection and documentation at the site, identify existing and potential
problems, solve them and recommend preventive steps and activities.
14.3 Ethical Considerations
Prior to study initiation the site will obtain IRB approval of the clinical investigation.
Any changes in the study protocol must be re-approved by the IRB. All subjects enrolled
for the study must provide their written consent prior to entering the study. The informed
consent form will be signed by the subject and retained by the investigator as part of the
study records.
14.4 Data Collection
Electronic Case Report Forms (ECRF’s) will be developed to collect the required data, as
described in this protocol. The ECRF include the following:
 Eligibility Form-Inclusion/Exclusion
 Demographic and Medical Information
 Epworth Results
 PTSD Questionnaire
 Nightmare Assessment
 WatchPAT200 Results Form
 Sexual Function Questionnaire
 Trial Termination Form
 EAA/T Session Report
 Adverse Event Form
 Serious Adverse Event Form
 Blood Test Results
The ECRFs are completed at the site and the site coordinator will conduct an initial quality check
before forwarding them to the data entry center. In some cases, Direct-Entry of Data into the
ECRF will be used and the ECRF will also be the source documentation. If a medical file exists,
the medical file will serve as the source documentation.
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14.5 Data Management
The data center will develop and maintain a database for the trial. Double data entry into
database will be used to reduce possibility of errors due to human entry, unless ECRF
(Electronic CRF) is used for the study.
The data will be entered from the CRF and inconsistencies will be resolved. Querying the
site for missing, incorrect or illegible data will be done at the core lab. Pre-entry and postentry quality control of the clinical data will be performed at the data center.
14.6 Adverse Event Reporting
In the case of adverse events experienced by a subject, the investigator will inform the
study monitor. The investigator will complete the adverse event form, including a
detailed description of the adverse event, date of experience, duration, severity, action
taken, relationship to the investigational device and the outcome of the event. The
adverse event form will be forwarded to the study monitor.
In case of serious adverse event the investigator should also inform the IRB committee.
15 PROTOCOL MODIFICATIONS
An investigator may propose an amendment to the protocol. The amendment will be
prepared and approved by the sponsor according to the company relevant SOP. The
amendment must be submitted to the IRB. When applicable, the amendment’s
implementation will take place only once approved by the IRB.
If, for any unexpected reasons, there is any requirement to deviate from the procedures
stated above, the protocol deviation should be discussed with the sponsor representative.
16 SUBJECT CONFIDENTIALITY
The subject’s name and personal data will remain confidential and will not be published
in any way. However, the sponsor’s monitor or representative and regulatory
representatives, auditors and inspectors may have access to medical files in order to
verify authenticity of data collected.
21
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Appendix 1: DSM classification of PTSD
According to The Diagnostic and Statistical Manual of Mental Disorders (DSM), PTSD
is considered to be one of the anxiety disorders.
PTSD sufferers experience intense psychological and emotional distress following a
traumatic event:
 Recurrent and intrusive recollections when exposed to internal or external events
 Remaining in a constant state of arousal
 Causing avoidance of emotions, socialization and reflection that may lead to
recurring memories and flashbacks
 Difficulty in falling and staying asleep
 Irritability or outbursts of anger
 Difficulty in concentrating
DSM-5 - Diagnostic Criteria for PTSD Released (May 2013)
PTSD criteria are being revised in order to take into account the things that have been
learned from scientific research and clinical experience.

Based on the proposed DSM-5 criteria, the prevalence of PTSD will be similar
to what it is currently in DSM-IV.

Symptoms are mostly the same. The 3 clusters of DSM-IV symptoms will be
divided into 4 clusters in DSM-5: re-experiencing, avoidance, negative
cognitions and mood, and arousal. It is proposed that a few symptoms will be
added and some revised.

Criterion A2 (requiring fear, helplessness or horror happening right after the
trauma) will be removed.

The diagnosis is proposed to move from the class of anxiety disorders into a new
class of "trauma and stressor-related disorders."

PTSD assessment measures, such as the PC-PTSD, CAPS and PCL, are being
revised by the National Centre for PTSD to be made available upon the release.
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