Dr. Nicole Culos-Reed
Summary and budget for each award currently held.
COPY OF SUMMARY AND BUDGET APPROVED BY THE CHILDHOOD CANCER
COLLABORATIVE STEERING COMMITTEE, ALBERTA CHILDREN’S HOSPITAL
Project title: Effect of physical exercise program on the immune system recovery
and quality of life in paediatric patients undergoing autologous stem cell
transplantation.
SUMMARY
Primary Objective: asses the effect of a combined exercise program (in and out
patient program) on immune cell recovery in patient undergoing a acute
hematopoietic stem cell transplantation (AHSCT).
Secondary Objective: determine if a moderate exercise program after an AHSCT
diminishes the deterioration of physical fitness, physical activity levels and improve
quality of life (QOL)
Third objective: To establish the program's feasibility.
Hypothesis
Based mainly upon intervention in adults and children with cancer and adults under
HSCT due to the lack of research in pediatric population undergoing HSCT (just two
previous research was done in the field of exercise related immune system
recovery) we hypothesize that moderate exercise training could improve the
immune system recovery, QOL and also diminish the physical fitness deterioration
in pediatric patients who have recently received an AHSCT. This improvement in the
immune system recovery is essential to diminish the risk of infection, relapse,
hospitalization days and improve the survival rate. In addition, improvement of
physical condition is vital to diminish the risk of fatigue and improve QOL.
Basic study design
This RCT (control and intervention group) will examine the effect of two phases
exercise program on several health related outcomes like immune system recovery,
physical fitness, quality of life, and physical activity levels in pediatric patient
undergoing autologous HSCT (figure 2). The intervention group is going to perform
an exercise program meanwhile the control group is going to continue conventional
treatment.
Both phases of exercise programs are going to be prescribed by an exercise
expertise based on previous experience and following the rules of the institutions
for global benchmarks for strength training and aerobic exercise in children and
adolescents [11,16,20,22].
The recruitment process will start in September 2011in the ACH and will remain
open until we reach 24 patients.
Dr. Nicole Culos-Reed
Statement of relevance to cancer investigation.
The main relevance of this research is to check if exercise could become a valid tool
as adjuvant therapy in the treatment of patient undergoing AHSCT and to create the
first community-based exercise program for this population in Calgary based on the
result of this intervention.
Due to increases in survival rates, the risk of developing different side effect (like
muscular atrophy, osteoporosis, diminish cardiorespiratory fitness, delay in
immune system recovery, increase fatigue status and deterioration of quality of life)
and the relative inactivity of this population, it is imperative that we adopt
strategies to promote active living to avoid the vicious cycle of deconditioning,
sedentary habits and fatigue. Enough evidence showed that these side effects might
be reverse at least in part by moderate and regular exercise practice. The
implementation of a combined supervised and home-based program would seem to
be a safe and feasible way to improve these variables.
It is also important to note that a previous work of our team is the only study that
has been published to date on the effect of physical exercise in the recovery of the
immune system in pediatric patient under HSCT. Due to the encouraging results of
this intervention [16] there is a growing demand to continue working in this field.
Dr. Nicole Culos-Reed
Complete Budget of research project
SALARIES
Position
1-Certified exercise
physiologist
2-Certified physical
trainer
Function
Fitness condition
assessment.
To assist Dr. Chamorro to
perform exercise training
session.
Cost
$7200 total assessment
3600$/year
$18,000/ 2year. $9000/year
Total
$12,600/year.
Justification personnel budget
1- Certified Exercise
CEP is necessary for baseline, 30 days and 10 weeks
Physiologist (CEP)
physical fitness assessment of 24 patients.
Rate 24 test x 3 assessment x $100 = $ 7200
2- Certified Exercise Training
Is needed to asses Dr. Chamorro in the training program
at the hospital and at the University of Calgary.
SUPPLIES
Endurance capacity assessment and others supplies.
Endurance capacity assessment
Material
Face mask model 8900 serie 8950 part number 669053
Face mask model 8900 serie 8960part number 669072
Face mask model 8900 serie 8940 part number 669052
Face mask model 8900 serie 8930 part number 669051
Y shape two ways non rebreathing valves part number
112418-2630
Y shape two ways non rebreathing valves part number
112414-2730
Headgears part number 200525
Headgears part number 201079
Quantity
1 x pediatric small
1 x pediatric large
1 x adult small
1 x adult medium
1 x size medium
Price
each
$82
$82
$69
$69
$446
1 x size large
$ 474
2x Size large
2x Size pediatric
large
1
$ 37
$44
Adapter to large and small mask adapter to medium Y
shape valve. Part number 200584
Adapter to large and small mask adapter to large Y shape 1
valve. Part number 200583
Adult small or medium mask adapter to large Y shape
1
valve. Part number 200542
Adult small and medium mask adapter to medium Y
1
shape valve. Part number 200543
Manual to use
TOTAL
$93
$93
$93
$93
$35
$1791
Dr. Nicole Culos-Reed
Justification Budget: All fitness tests are going to be performed in the Thrive Lab. There
we will have all the necessary equipment to perform these evaluations except the mask
and other supplies detailed above that are needed to perform aerobic capacity test in
children. Since the intervention is going to involve a very wide range of age (5-18) we are
going to need different sizes to cover the whole population.
Others supplies
Material
Photocopying, printing
Laptop
Quantity
Price each
$1500
$1500
1
TOTAL
$3000
Justification Budget: these supplies will be needed for printing QOL questionnaires and
manuals. The laptop are going to be used for database management at the ACH.
EQUIPMENT
Under this point come in: fitness equipment, physical activity levels
assessment/accelerometers and physical activity intensity control of training /
heart rate monitors.
Fitness Equipment
Material
Minor fitness equipment
Reaction ball
Z ball
Soft weight set of all six
Heavy bar 6lb 48’’
Heavy bar 4lb 24’’
Heavy bar 9 lb 48’’
PVC Medicine ball 4kg
Fit ball 30 cm
Multi active balance stone
Fitter active sit up disc
Polar bear
Classic exercise ball chair 45 cm
Classic exercise ball chair 55 cm
Classic balance board
Bosu
Lifeline resistance Cable Teal
Lifeline resistance Cable Purple
Lifeline resistance Cable Pink
Slastix very light 4 foot resistance
Quantity
Each price $
1
1
2
1
1
1
2
2
2
4
1
2
2
1
2
3
3
3
2
10.95
13.95
51.96
34.95
24.95
39.95
39.95
19.95
49.95
9.95
39.95
29.95
34.95
34.95
109.95
15.95
15.95
15.95
13.95
Dr. Nicole Culos-Reed
Slatix light 4 foot resistance
Slatix medium 4 foot resistance
Hop ball
Gliding discs hardwood
Mat strap
Hoola Hoop 3 lb
Total minor equipment (ME)
Total ME plus 40% discount
Games
Cardiovascular equipment
Total body kids cycle
Platinum Club Series Recumbent Lifecycle
2
2
1
4
6
3
13.95
13.95
29.95
19.95
4.95
37.95
1367.67
$820.60
$250
{model 664 (8 to 11
years old)
2195
R1 lifecycle achive
3500
1 (model 602, 9
2195
years up)
1 (model 601, 5 to 12
Elliptical trainer
2195
years)
Total cardiovascular equipment
$10,085
Total fitness equipment
$11,155.6
Justification Budget: All these equipment are going to be used during inpatient training.
We need to cover a very wide range of age (5 to 18) for this reason different sizes of all
equipment are needed. Games with different materials such as balls, hockey sticks, tennis
rackets, are going to be played during training sessions to ensure high adherence. Upon
completion of this research, all these equipment will remain in the hospital and are going
to be available to all patients under HSCT.
Elliptical trainer



We are going to buy the minor equipment in Fitter (www.fitter.com)
We are going to buy games (balls, hockey, tennis, basketball) in Toys r us and Wallmart.
We will buy the cardiovascular fitness equipment in Fitness Kids Fitness equipment and
lifefitness (www.fitnessandkids.com, www.lifefitness.com)
Physical Activity Levels Assessment / Accelerometers
Device
Quantity
Price each
Actical accelerometer (Phillips – Respironics, Oregon,
10
$475
USA)
Waist band
10
$8
Reader and software
1
$525
Total
$5355
Justification of budget: This device is the gold standard measure of physical activity levels.
We are going to asses physical activity levels to determine if a physical exercise
intervention may diminish the acquisition of sedentary lifestyle.

See, www.bio-lynx.com
Dr. Nicole Culos-Reed
Physical Activity Intensity Control of Training / Heart Rate Monitors
Device
Quantity
Price each
RS300X Polar heart rate monitor
10
$189.99
Total
$1899.9
Justification of Budget: We need to control Heart Rate during training session to achieve
the physiologist benefit of training. We just need ten because we don’t expect to have
more than ten patients training at the same time.
See, http://www.polarca.com
OTHERS
Under this point are included parking reimbursement and immune system
assessment
Parking reimbursement
Function
Parking
Support personal trainer (trainee at ACH)
Parking
Support children assessment (24 patient, 4
times assessment * x 5$ each.
* We include a familiarization session pre baseline assessment
Total
Cost
$2000
$480
$2480
($1240/year)
Justification Budget: this budget is entirely dedicated to cover parking expenses of parents
who come to ACH with their children for the assessment session and also the support
personal trainer.
Immune System Assessment:
Items
DNA based studies
KIR genotyping
SSP based allele typing for KIR
genes
RNA based study
KIR gene expression analysis
Flow based studies
Blood cell leukocyte analysis
KIR protein analysis
NK cell function analysis
Budget Total:
Cost
$625
$2400
$9000
$9000
$8100
$13500
$ 42,625
Dr. Nicole Culos-Reed
Justification of budget:
A total of 24 autologous HCT patients will be recruited for the study. We are expecting
50% of these transplants will be tandem transplants. For all tandem transplant patients,
assessment of immune recovery, KIR expression and NK cell function will be performed at
9 time points: Pre transplant, day 7, 14, 28 after 1st transplant and day 7, 14, 28, 56 and 84
post 2nd transplant. For all single transplant patients, assessment of immune recovery, KIR
expression and NK cell function will be performed at 6 time points: Pre transplant, day 7,
14, 28, 56 and 84 posttransplant.
The budget for DNA based studies is therefore requested for 24 samples.
The budget for RNA and flow based studies are therefore requested for a total of 180
samples that include (i) 72 samples for 12 patients undergoing single transplant and (ii)
108 samples for 12 patients undergoing tandem transplants.
DNA based studies (KIR genotyping analysis)
1. KIR genotyping will be performed for 16 KIR genes. Cost of performing genotyping
for 16 KIR genes for one sample is $25 (including cost for reagents, consumables,
Luminex supplies). Given that a total of 25 samples (24 patients and negative
control) will be genotyped, total cost requested for KIR genotyping is $625.
2. Sequence specific primer (SSP) based typing will be performed for KIR alleles. Cost
of SSP typing per sample is 20$. Considering that on average 5 KIRs gene will
allelotyped for all 24 patients, a total of 120 samples will be SSP typed, total cost
requested for SSP based allele typing is $2400
RNA based studies (KIR Gene expression analysis) :
3. Real time quantitative PCR analysis will be performed for gene expression analysis
KIR genes. Cost of one sample analysis for all KIR genes is $50 (including reagents
for RNA extraction, cDNA preparation, SYBr green based Q-PCR analysis,
consumables and technologists time). Given that a total of 180 samples will be
analyzed, total cost requested for KIR gene expression analysis is $9000
Flow cytometry based studies (blood cell leukocyte, KIR expression and NK cell
function):
4. Blood leukocyte analysis will be performed for assess the recovery of different
blood leukocyte subsets after HCT. Cost of one sample analysis for 12 cell surface
markers is 50$ (including including flurochrome labelled antibodies, flow reagents,
consumables and technologist time). Given that a total of 180samples will be
analyzed, total cost requested for KIR gene expression analysis is $9000
5. KIR protein expression will be performed by flow cytometric enumeration of KIRs
on NK cells. Cost of one sample analysis for 7 KIRs is 45$ (including flurochrome
labelled antibodies, flow reagents, consumables and technologist time). Given that
a total of 180 samples will be analyzed, total cost requested for KIR gene
expression analysis is $9000
Dr. Nicole Culos-Reed
6. NK cells function will be assessed by invitro flow cytometric enumeration of
degranulation and cytokine production by NK cells. Cost of one sample analysis for
7 KIRs is 75$ (including flurochrome labelled antibodies, K562 cell lines, culture
reagents, flow reagents, consumables and technologist time). Given that a total of
180 samples will be analyzed, total cost requested for NK cell function analysis is
$13500
Budget overlap with the studies proposed in the research program on
Immunogenetic Biomarkers for the pathogenesis and therapy of
complications of paediatric HCT.
The two studies have significant overlap in terms of laboratory experiments and
therefore there are budgetary overlaps too. Following table shows how these
overlaps were taken into consideration in the proposed budget
Items
Study#1
Study#2
Proposed study Study on
Immunogenetic
Biomarkers
KIR
16 KIR genes:
16 KIR genes: SSO
genotyping SSO based
based typing
typing
Cost per sample : 25$
Cost per sample:
25$
KIR allele
typing
SSP based
Sequencing based
typing
typing
Cost per sample: Cost per sample: ~58$
20$
KIR gene
expression
analysis
Quantitative
Quantitative Real time
Real time
PCR
Cost per sample: Cost per sample: 45$
50$
Blood cell
leukocyte
analysis
Flow Cytometry Not included
Cost per sample:
50$
Comments
Since all samples will be
batched and the experiments
will be performed by the
postdoctoral fellow hired from
funding for study#2, no extra
money has been requested for
the technologist time
Since high resolution allele
typing by sequencing is not
required to meet the objectives
of the proposed study, SSP
typing has been included. No
extra money has been
requested for the technologist
time
Since the experiments for the
gene expression analysis will
not be batched and will be
performed by the technologist a
marginal cost (5$ per sample)
has been included for
technologist time
The lab experiments have no
overlap with study#2
Dr. Nicole Culos-Reed
KIR
protein
analysis
Flow Cytometry: Flow Cytometry; 5 KIR
7 KIR genes
genes
Cost per sample: Cost per sample: ~30$
45$
NK cell
function
analysis
In vitro culture
Not included
and intracellular
cytokine
staining
followed by flow
cytomteric
analysis
Cost per sample:
75$
Dr. Faisal Khan faisal.khan@cls.ab.ca
Proposed study includes 2
addition KIR proteins, therefore
an additional cost of 10$ per
sample has been included. Since
the experiments for the KIR
protein analysis will not be
batched and will be performed
by the technologist a marginal
cost (5$ per sample) has been
included for technologist time
The lab experiments have no
overlap with study#2
Dr. Nicole Culos-Reed
Summary of total budget required in 24 month
Salaries
Employee Benefit at %
Supplies
Equipment
Travel
Others
Total
$ 25,200
$ Include above
$ 4791
$ 18,410.5
$0
$ 45,105.0
$ 93,506.0
Summary of budget required to the CCC in 24 month
Salaries
Employee Benefit at %
Supplies
Equipment
Travel
Others
Total
$0
$0
$ 1791
$ 18,410.5
$0
$ 42,625
$ 62,826.5
Certified exercise physiologist would be covered by Tanya's salary supported by the
Thrive Lab. Some aid/help by Research assistant can be covered by existing grants,
but will need other funding to cover the total amount. We are going to submit grants
to the CIBC, Childhood Cancer Foundation, Calgary Foundation, and Alberta Center
for Child Family and Community Research.
We submitted a proposal to Nintendo America to become our sponsorship. We don’t
have any answer yet, but with his sponsorship we will cover Parking
reimbursement, others supplies and part of the research assistant salaries.
We already submitted a proposal to the Alberta Children’s Hospital Research
Institute for a $3000. We don’t have an answer yet.
Dr. Nicole Culos-Reed
FORMAL AWARD LETTER
Dr. Nicole Culos-Reed
COPY OF SUMMARY AND BUDGET APPROVED BY THE ALBERTA CHILDREN’S
HOSPITAL FOUNDATION (Small research grants).
Project title: Effect of physical exercise program on the immune system recovery
and quality of life in paediatric patients under autologous stem cell transplantation.
SUMMARY
The use of high dose chemotherapy combined with autologous hematopoietic stem
cell transplantation (AHSCT) has improved the outcome of hematologic
malignancies. Neverthless, AHSCT is associated with several transplant related
toxicities which compromise full rehabilitation and result in diminished physical
condition, functional capacity, fatigue during activities of daily living and decreased
quality of life (QOL) [2, 3]. The health benefits of regular exercise training in adult
cancer patients/survivors, are promising and include improved immune function
[4-7], diminish pain, improved physical fitness [4, 8-12], and quality of life [13].
Our research objectives are:
1- Asses the effect of a 3-week exercise intervention performed during inpatient
stay for AHSCT on immune cell recovery.
2- To determine if an intervention of exercise after AHSCT could diminish the
deterioration of physical fitness and increase physical activity levels.
3-To establish the program's feasibility in this sample, in order to run a multi-centre
research with a larger population in the future.
A total of 24 children (ages between 5 -18) will be recruited for this trial; 12
subjects will be assigned to the exercise training program and 12 subjects will be
assigned to the control group (usual care). Children in the exercise group will
participate in an intra-hospital individually supervised exercise program including
both resistance and aerobic training (designed based on our previous experience
and following the rules of the institutions for global benchmarks for strength
training and aerobic exercise).All outcome variables will be assessed at preintervention and post-intervention ( +30 days post-HSCT) in both groups.
We will assess the effect of an exercise program on: natural killer cell activity,
leukocyte count, citokines enviroment, quality of life and fitness condition.
Dr. Nicole Culos-Reed
Project Budget:
Material
Quantity
Each price $
Static Bike. Model: 664 Total Body Kids 1
2195
Cycle
(web link: www.fitnessandkids.com)
Minor Fitness Equipment.
See all the list
(web link www.fitter.com)
below.
Reaction ball
1
10.95
Z ball
1
13.95
* Soft weight set of all six
2
51.96
*Heavy bar 6lb 48’’
1
34.95
*Heavy bar 4lb 24’’
1
24.95
*Heavy bar 9 lb 48’’
1
39.95
*PVC Medicine ball 4kg
2
39.95
*Fitball 30 cm
2
19.95
Multi active balance stone
2
49.95
*Fitter active sit up disc
3
9.95
Polar bear
1
39.95
*Classic exercise ball chair 45 cm
2
29.95
*Classic exercise ball chair 55 cm
2
34.95
*Classic balance board
1
34.95
*Lifeline resistance Cable Teal
1
15.95
*Lifeline resistance Cable Purple
1
15.95
*Lifeline resistance Cable Pink
1
15.95
*Slastix very light 4 foot resistance
1
13.95
*Slatix light 4 foot resistance
1
13.95
*Slatix medium 4 foot resistance
1
13.95
Hop ball
1
29.95
Total minor fitness equipment
29
801,12
TOTAL: $ 2996,12
Justification of budget
The fitness equipment is going to be used during the daily exercise program for the
intervention group in the Alberta Children’s Hospital. Upon completion of the trial,
the equipment will remain within the paediatric oncology group to encourage an
ongoing exercise program for the in-patient population.
We need different elastic band resistances and weights due to the potential range in
participants, from 5 to 18 years of age.
FitterFirst International will provide all equipment (other than the bike – see
attached quote).
Budget that funding for other aspects of the study (personnel, immunological
markers, is being applied for in separate grants).
Dr. Nicole Culos-Reed
FORMAL AWARD LETTER