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CSCC/BMAP/2011/01
Chaitanya
Hospital
Clinical Trial Protocol for Stem Cell Therapy and
Research
Study title: A open label clinical trial to study the safety and efficacy of Bone
marrow derived autologous cells for the treatment of Acute paraplegia.
Protocol number: CSCC/BMAP/2011/01, Version 01
Phase of the study: Phase 2 / Phase 3
Institution conducting the trial:
Chaitanya Hospital,
Rahi-sakha Apartment, Parvati Payatha, Pune.
Contact Telephone-8087799092; Fax no.: 24329666
Sponsor:
Dr. Anant Bagul
Chaitanya Hospital, Rahi-sakha Apartment, Parvati Payatha, Pune.
Contact Telephone-8087799092; Fax no.: 24329666
Email id.: anantbagul@yahoo.com
Names of Principal Investigator and Co-investigators:
Principal Investigator:
Dr. Anant Bagul
Chaitanya Hospital, Rahi-sakha Apartment, Parvati Payatha, Pune.
Contact Telephone-8087799092; Fax no.: 24329666
Email id.: anantbagul@yahoo.com
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2. Introduction:
Stem cells bridge the gulf between the fertilized egg that is our origin and the architecture
that we become. They supply the cells that construct our adult bodies and, as we age,
replenish worn out , damaged and diseased tissues. They renew themselves, resisting the
powerful pull towards differentiation that overcomes more prosaic cells. And depending
on the source, they have the potential to form one, many or all cell types of an organism.
There are important distinctions, distinctions, however, regarding how developmentally
plastic these cells are; that is, how many different paths they can follow and to what
portion of a functioning organism they can contribute. Totipotent stem cells are cells that
can give rise to fully functional organism as well as to every cell type of the body.
Pluripotent stem cells are capable of giving rise to virtually any tissue type, or cells such
as nerve cells, but not a functioning organism. Multipotent stem cells are more
differentiated cell (that is , their possible lineages are less plastic/ more determined ) and
thus can give rise only to a limited number of tissues.
Stem cells have two important characteristics that distinguish them from other types of
cells. First, they are unspecialized cells that renew themselves for long periods through
cell division. The second is that under certain physiologic or experimental conditions,
they can be induced to become cells with special function such as the beating cells of
heart muscle or the insulin- producing cells of the pancreas as well as the neurons of
brain.
Here at Chaitanya hospital and proposed research centre we have decided to use stem cell
in neurologically compromised patients between 3 to 70 years old cases due to various
cause and study the pattern of recovery and hence efficacy of stem cells.
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3. Study Objectives:
a) Primary Objective: - To evaluate the efficacy of bone marrow derived stem cells in
patients with cerebral palsy above 15 years.
b) Secondary Objective: - To evaluate the safety of the bone marrow stem cells in
patients with cerebral palsy above 15 years.
4. Study plan
a. Study design: This study is an open label single arm; single center trial to check safety
and efficacy of Bone marrow derived autologous cells (100 million per dose) in patients
with cerebral palsy above 15 years.
b. Number of patients: 100
c. Inclusion criteria:
 Should suffer from Acute Paraplegia due to pyramidal or extra-pyramidal cause.
 Willingness to undergo Bone marrow derived autologous cell therapy
 Ability to comprehend the explained protocol and thereafter give an informed
consent as well as sign the required Informed Consent Form (ICF) for the study.
 Ability and willingness to regularly visit the hospital / clinic for follow up during
the follow up period / on prior agreed time points as per the protocol.
d. Exclusion criteria:
 Patients with pre-existing or current systemic disease such as lung , liver
(exception: history of uncomplicated hepatitis A) gastrointestinal , cardiac,
immunodeficiency (including HIV) or any other condition determined by history
or laboratory investigation that could cause a neurological defect (including
syphilis, clinically relevant polyneuropathy) etc.
 History of life threatening allergic or immune-mediated reaction.
 Haemodynamically unstable subjects.
 Subjects suffering from peripheral muscular dystrophy.
 Severe skin infection and osteomyelitis/ or at the site of bone marrow aspiration
potentially limiting the procedure.
 Positive test results for Hepatitis A and Hepatitis B or C.
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 Alcohol and / or drug abuse/ dependence.
 Subjects with primary or secondary diabetes, insulin dependence or with serum
creatinine > 1.5 mg/dL.
 Neurological disease caused by autoimmune or genetic cause.
e. Chart of schedule of visits and activities at each visit:
Activities
Screeni
ng
Treatment
1
Visit
Day 1
Day 3
1days)
Informed consent
Medical history
Physical
Examination
Vital Signs
Haemogram
YE
S
YE
S
YE
S
YE
S
YE
S
YE
S
Treatment
2
Treatment
3
Visit 1
Visit 2
Visit 3
Day14
(+2days)
Day24
(+2days)
Week
6 (+ 10
days)
Week 12
(+10 days)
Week 24 Week
36
(+10days (+10 days)
)
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
(-
Visit 4
YES
YES
YES
YES
YES
YES
HIV/Hepatitis
B&C
YE
S
YE
S
YE
S
Renal
test
Function
YE
S
YES
YES
Liver function test
YE
S
YE
S
YES
YES
Coagulation tests
Bone
marrow
aspiration
YES
YES
YES
Administration of
Adult stem cells
YES
YES
YES
MRI
Electrocardiogram
Chest X- ray
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urinalysis
Adverse Events
Concomitant
Medication
YE
S
YE
S
YE
S
CSCC/BMAP/2011/01
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YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
YES
f. Ethical considerations – risks and benefits
i. Screening Phase: Clinical Evaluation of Patient to rule out Life threatening conditions
and to rule out other exclusion criteria. Investigations are without any risk.
ii. Treatment phase: Bone marrow aspiration is a standard Clinical procedure well
documented in medical practice and involves negligible risk, Bone marrow aspiration is
done in strict aseptic condition in Major Operation theatre.
Procedure: Intrathecal transplantation of stem cells
ii. Post – treatment phase: Monitoring of patients is done as per SOP for lumbar
puncture and monitors vital signs and treatment minor side effect like headache, nausea
or any other adverse effect for 24 hours
iv. Withdrawal of patients prior to study completion: The study will include all the
subjects who have provided their written informed consent at the screening visit.
Bone marrow aspiration will be performed for all subjects for separating of
Mesenchyamal stem cells and mononuclear cells from bone marrow cells. The cells
obtained will be separated using centrifuge method. In conditions where the bone marrow
fails to provide a sufficient amount of cells the investigator will decide to either
discontinue the patient or to repeat the aspiration for second bone marrow patients who
discontinue will not receive other standard treatment care will continue as per the
discretion of the investigator.
g. Efficacy assessment
i. Primary efficacy outcome:
 Improvement in overall sensory for motor control using Frankel score.
 Improvement in sensory and motor dysfunction using ASIA scale (American
spinal cord injury association)
ii. Secondary efficacy outcome
 Improvement in bowel and bladder control.
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5. Safety assessment
Definitions:
Adverse events: - an adverse event is any undesirable experience concerning the health
of patient occurring during clinical trail whether or not considered related to the study
treatments. It is an unfavourable an unintended diagnosis , symptoms, signs, syndrome or
disease that occur during a study , if absent at baseline, or present at baseline , appears to
worsen.
The term adverse event could refer to any of the following events which either develops,
increase in severity, or increase in frequency during the course of the study:a) any signs observed by the investigator
b) any symptoms reported by or elicited from the subject
c) any abnormality detected during physical examination
d) any clinical significant laboratory abnormality.
Serious Adverse Event: - a serious event (experience) or reaction is any untoward
medical occurrence that at any dose;
a) Result in death
b) Is life-threatening
c) Result in persistent or significant disability/ incapacity
d) Requires inpatient hospitalization or prolongation of existing hospitalization
e) Is a congenital anomaly/ birth defect
f) Requires a medical or surgical intervention to prevent any of the outcomes which
would have in the view of the investigator otherwise occurred.
ii. Documentation of adverse events:
Adverse Events will be documented in source document and will be simultaneously
captured in the respective section of case record forms.
Serious adverse events will be documented in the source document as well as it will be
captured in Serious adverse event log.
iii. Reporting of serious adverse events:
Adverse events will be reported to Ethics committee on a periodic basis.
Serious adverse events will be reported to the sponsor within 24 hrs telephonically as
well the SAE form will be reported to the Ethics committee within 7 working days and to
the concerned regulatory within 14 working days.
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6. Concomitant Medications
i. Documentation of medications – name, dose, duration of the concomitant medications
will be documented in case record forms.
ii. Intercurrent illness: Any major systemic illness like DM, HT, Autoimmune disorders
will be recorded for observation or checking inclusion/exclusion criteria and will be
documented in source document.
iii. Prohibited medications: Steroids, Hypnotic drugs, muscle relaxants.
7. Product information, dose scheme and administration instructions
i. Product information: Centrifuged sample of bone marrow containing 10 million
MNC
ii. Dose Scheme: Same as explained in visit schedule on page no.4
iii. Route of administration: Intrathecal
iv. Cell preparation and transplantation instructions: Cell sepration will be done as
per the standard lab SOP which is maintained at Chaitanya Stem cell center laboratory.
Cell transplantation will be done as per the “Bone marrow extraction and Transplantation
manul” maintained at Chaitanya Hospital.
8. Data evaluation / Statistics: Statistical analysis plan and data evaluation will be done
at the end of the study period.
9. Ethical and Administrative Issues
a. Patient’s / Parent / Relative’s Informed consent: Informed consent will be obtained
for the patient/ parent before the study participation.
b. Institutional Ethics committee approval: will be obtained before the start of study.
c. Adherence to the protocol: Study staff will try to show 100% compliance with the
protocol. In case of any deviation for the protocol protocol deviation form will be filled.
For any deviation before the participation of subject a waiver will be requested to the
sponsor, if granted the subject will be continued or will be dropped from the study.
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d. Protocol amendment approval: Protocol amendments will be notified to the Ethics
committee and approval for the same will be seeked.
e. Data collection, source documentation and retention of patient: Data will be
collected in respective source document and will be maintained secured in lock with
respective trial personnel.
10. Confidentiality and publication: Confidentiality of the patient data will be
maintained the subject records will only be assessable to the trial staff and to the
regulatory personnel’s only.
The data obtained from the trial will be published & presented in Conferences and
journals.
12. Enclosures
1.
Case Record Form
2.




Administrative approvals:
IEC ( of each center)
Approved patient information sheet and consent form
IC-SCRT / NAC-SCRT approval if required
Investigators bio – data
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