Protocol Application Reviewed by Children’s Hospital and
Regional Medical Center IRB
A. Background or rationale for this
activity. Cite previous work in the area by you and others with an emphasis on
the problems or deficiencies in the existing data base. Include specific
bibliographic references for all work cited.
Type 2
diabetes (the most common form of diabetes) used to be found almost exclusively
in adults. However, in the past 10 years, the incidence of type 2 diabetes
among children has increased dramatically (about 10 fold). This increase seems
to be due to a simultaneous increase in childhood obesity. Asians are a rapidly
growing minority group in the
The risks of diabetic complications, such as renal
failure, lower extremity amputation, blindness, and cardiovascular disease,
increase with duration of diabetes. Thus, the increased prevalence of type 2 diabetes in children is especially
concerning. Based upon observation from studies among adults, Asian-American
children are probably at increased risk for type 2 diabetes, yet they are an
under-studied group. Since the risk of childhood type 2 diabetes is maximal
around age 13.5, it appears that important physiologic changes occur during
puberty that increase the risk of diabetes. The proposed study will provide important information on the
metabolic features of the insulin resistance syndrome in Japanese-American
children as they progress through puberty, and will also provide an opportunity
to better understand the effect of Japanese ancestry on metabolic risk. These
studies will probably be relevant to other Asian populations in the
B. What specific
question(s) does this project attempt to answer?
The long-term aim of this study is to better
understand in children the metabolic changes that precede the development of
type 2 diabetes, and the influence of Asian ethnicity on diabetes risk.
Prepubertal children of varying proportions of Japanese ancestry (ranging from
0 to 100%) will be followed into and through puberty.
Specific aim 1: To describe in prepubertal (8-10 years),
nondiabetic children the metabolic and obesityrelated factors that are
associated with the insulin resistance metabolic syndrome. These include
fasting plasma lipids (cholesterol, triglycerides, HDL-cholesterol, and
LDL-cholesterol), LDL size, blood clotting factors (plasminogen activator
inhibitor-1, fibrinogen, C-reactive protein), glucose, insulin, C-peptide, and
proinsulin; glucose tolerance, total body fat,; body fat distribution; and body
mass index.
Hypothesis 1: Features of the metabolic syndrome (abnormal response to
insulin, high blood pressure, and abnormalities of blood cholesterol and other
lipids) are found in some prepubertal children.
Specific aim 2: To assess the ability of cells in the pancreas
to make insulin by measuring fasting plasma insulin, C-peptide, proinsulin, and
acute insulin response to glucose by an intravenous glucose tolerance test.
Hypothesis 2: Pancreatic islet B-cell dysfunction is evident
in some children.
Specific aim 3: To describe the changes in these factors as
children progress through and complete puberty. Tanner staging is used and
plasma testosterone, estradiol, DHEA-S, IGF, IGFBP-3 are measured to describe
pubertal stage.
Hypothesis 3: Puberty is associated with changes in body fat
distribution and metabolic parameters in a direction consistent with higher
risk
of glucose intolerance and cardiovascular disease.
Specific aim 4: To
describe the relationship of lifestyle factors (diet and physical activity) to
the metabolic and adipose factors, and changes therein.
Hypothesis 4: Diet and physical activity are important
predictors of body fat and metabolic changes in children.
Specific aim 5: To describe the relationship of proportion of
Japanese ancestry to the metabolic and obesityrelated factors, and changes
therein.
Hypothesis 5: A higher proportion of Japanese ancestry is
associated with a greater predisposition to the metabolic syndrome and
diminished insulin secretion.
C. Explain how this project is
specifically designed to answer the questions being asked (e.g., caselcontrol
comparison; randomized double-blind trial).
This is longitudinal, observational study of prepubertal
children.
D. Describe how
your data will be recorded, including the outcome variables and the methods for
analysis to be used. Submit data
collection sheets, if available. NOTE: Statistical consultation is encouraged.
Data will be
entered into a data management system on a microcomputer for storage and
analysis. The outcome variables of primary interest in this study are B-cell
function, body fat distribution and other features of the metabolic syndrome:
blood pressure, dyslipidemia, insulin resistance, and hyperinsulinemia. As
indicated by the 5 specific aims of this research, 5 hypotheses are being
addressed, and data analysis will be used that is appropriate to each
hypothesis and aim. In general, we hypothesize that the listed metabolic
features are influenced by environmental factors (sedentary lifestyle and high
caloric, high fat diet), pubertal development, and ethnicity: Linear regression
and analysis of covariance (ANCOVA) will be used to test these hypotheses. The
specific statistical methods are described in detail in the grant application.
In order to understand the features of the metabolic syndrome in children and
adolescents, we plan to measure the change in these variables before puberty
(baseline) and at 2-year follow-up, when approximately 42% of children will
have entered early to mid-puberty (breast Tanner stage 2-3 or testicular volume
? 4ml.). This will allow the effects of puberty to be distinguished from the
effects of aging alone.
Because
individuals from the same family may share genetic and environmental factors,
analyses that include siblings or cousins may violate statistical assumptions
of independence. We anticipate few siblings given the small sibship size in
this population and the narrow eligible age range. Cousins share only 12.5% of
their alleles on average,
so we do not expect strong intercorrelations. Nevertheless, analyses
will utilize a robust variance estimator (or sandwich estimator) with kindred
as the clustering variable. This procedure uses a robust estimate of variance
and relaxes the assumption of independence for individuals from the same
kindred.
E. SUBJECTS:
|
How Many |
Age |
ange |
|
|
Current Year |
Entire Study |
Current Year |
Entire Stud |
|
|
300 |
8-10 o |
8-10 o |
|
|
0 |
|
|
|
|
150 Caucasian cousins |
8-10 yo |
8-10 yo |
Subiect Group
Normals/Controls
Patients
Other (specify, e.g., parents,
other family members,
school teachers)
2. Criteria for selection for each subject group.
Healthy prepubertal children, aged 8-10, who are
either of Japanese ancestry (any proportion) or are Caucasian cousins of mixed
Japanese-Caucasian participants will be eligible for this study. Participants
must anticipate living in the
3. Criteria for exclusion for each subject group.
Children who are non-English speaking, and children who
do not have an English speaking parent will be excluded. Children who are on
chronic medications will be excluded; however, children with recent antibiotic
use for an acute illness may participate. Girls with Tanner breast stage >_
2 and boys with testicular volume >_ 4 ml at baseline will be excluded.
Children who are unable to cooperate with the study protocol (IV placement, lie
still for imaging procedures without sedation) will also be excluded.
4. Source of subjects.
Include letters of cooperation, as appropriate, from agencies or other
institutions involved in subject recruitment.
We
will use existing contacts in the Japanese American community to recruit
children of Japanese descent and Caucasian cousins of mixed Japanese-Caucasian
participants. These include our Community Advisory Board members (see http://dept.washington.edu/jacds/).
This is a critically important aspect of this research
and we will depend heavily upon the experience we have gained and the extensive
networking we have established over the past two decades in performing the
Japanese American Community Diabetes Study. We will recruit children of Japanese
ancestry through a variety of techniques
that have proven to be successful in the past. Letters will be sent to the
approximately 600 living adult participants in our Japanese American Community
Diabetes Study, residing in King County, Washington, informing them about the
expansion of our study to include children and asking them to contact us if
they know of eligible children who may be interested (see attached draft of
recruitment letter). Our website (http://depts.washington.edu/jacds/)
will include recruitment information. We will also carry out community-wide
publicity through community events and activities as arranged through our
Community Advisory Board (such as writing articles for the Tayori newsletter
and participating in church bazaars). We will send information and recruitment
letters to Japanese households in
5. Does subject population Include equitable gender and minority
representation?
[ ] Yes [X] No, explain
Gender representation: Male and female subjects will be
enrolled on a 50/50 basis.
Minority
representation: The study focuses on children of partial to full Japanese
descent, and Caucasian cousins of mixed Japanese-Caucasian participants.
Asian Americans are a diverse population. Japanese
Americans are the third most populous Asian subgroup in
Another important reason to focus on Japanese Americans
is their history of participation in similar local studies. We have conducted
the Japanese American Community Diabetes Study in adults since 1983, with
superb participation and cooperation by the Japanese-American community, and
this will provide an excellent basis for recruitment of children for this
study.
6. How and by whom
will the subjects be approached? Explain what steps you will take to avoid
coercion and to protect privacy. (NOTE: In most cases, parents or guardians
should be approached before giving information to the minor.) If to be used,
submit adverfsements/flyers/contact letters, explaining how and where they will
be distributed. For information about recruitment advertisements within CHRMC,
call 526-2023.
See above
recruitment strategies. Current participants in the Japanese American Community
Diabetes Study already receive an update newsletter from us. Parents or
guardians of eligible children who are interested in joining the study will
contact us privately and directly through phone call, email or written response
to an
enrollment flyer. In addition, a flyer may be provided to
our contacts in Japanese American community organizations for inclusion with
their routine mailings. This flyer will be developed with input from our
Community Advisory Board. Prospective participants' names are kept confidential
among study personnel. (See attached letter of support from Dr. , chair of our Community Advisory
Board)
Those children (and their parents or guardian) who are
interested in joining the study will contact us privately and directly through
phone call, email or written response to an enrollment flyer. Recruiters who
are not actual members of our study personnel will not be advised of the names
of those they have successfully recruited.
7. Will subjects receive
an inducement, e.g., payment, services without charge? If so, what amount or
how? What is the reason for this inducement?
Participants will
be offered compensation for time and discomfort in the form of gift
certificates. Twentyfive dollar gift certificates will be provided for each
evaluation. Children will be allowed to select from a wide range of gift
certificates, such as movie theaters, video rental, sporting events, activities
(such as miniature golf or
bowling), and toy stores). Parking vouchers will be provided to parents.
F.
PROCEDURES INVOLVED. Provide a short description of the sequence and methods to be used,
e.g., administration of drugs, volume of blood, size of biopsy, questionnaire,
name of psychological test. Include procedures planned for screening and followup phases. If audiovisual, tape recordings, or
photographs will be made, describe their use. Add sheets if necessary.
Evaluations will take place at the University of
Washington General Clinical Research Center (GCRC) pediatric satellite facility
at Children's Hospital and Regional Medical Center. Information about
ethnicity, dietary and physical activity habits, pubertal maturation, and
features of the metabolic syndrome will be obtained at baseline. All
participants must be prepubertal at baseline. All children will be re-examined
at 2 years. At 2 years, about 42% of participants will be pubertal, allowing
the effects of early- to mid-puberty to be distinguished from the effects of
aging.
The following information will be obtained from the
child's parent. Demographic information will include date and country of birth,
years of US residence, non-English language use, parental educational level,
and household income. If the child's parents are divorced, the custodial parent(s)
will be determined and the household income adjusted accordingly. For example,
if a child resides 40% of the time with the father and 60% of the time with the
mother, the child's household income will be calculated as 0.4*(father's
household income) + 0.6*(mother's household income). A brief medical history
will be obtained to confirm that the child has no chronic medical problems and
is not acutely ill, as well as questions about medications, body odor/deodorant
use, menarche (girls) and voice change (boys). Family history of medical
conditions (diabetes, heart disease, hypertension, hyperlipidemia, or stroke)
and ethnicity of parents and grandparents will be obtained.
Standing height will be measured without shoes to the
nearest 0.lcm. Body weight in light clothing, without shoes, will be measured
to the nearest 0.01kg. BMI will be calculated (kg/m2). Two waist
circumferences will be measured with a nonelastic tape: at the superior margin
of the iliac crest and at the midpoint between the iliac crest and the lowest
rib margin in the mid-axillary line. Hip circumference will be measured at the
maximum extension of the buttocks. Supine blood pressure will be measured using
a mercury column sphygmomanometer and an appropriately sized cuff three times,
and the mean of the second and third measurements will be used to estimate
systolic and diastolic blood pressure. Heart rate will be counted at the radial
pulse for 15 seconds to calculate beats/minute.
An experienced clinician will examine the neck and skin
folds for the presence or absence of acanthosis nigricans. Visual inspection of
the breasts (female), genitalia (boys), and pubic hair will determine Tanner
stage of sexual development. Testicular volume will be measured in boys using a
Prader orchiometer. These standard techniques for determining sexual maturation
have been shown to be appropriate for Japanese children. Because pubic hair
development is significantly slower in Japanese children compared to Caucasians,
despite earlier skeletal, genital and breast maturation by approximately one
year, primary analyses will not use pubic hair determinations of Tanner stage.
Sex hormone levels will be used to validate pubertal status (see section D2f).
Three-day food
records and 24 hour dietary recall will be used to measure dietary habits.
Because children have difficulty recalling dietary details, a registered
dietitian will educate children and parents about estimating portion sizes and
techniques for recording dietary intake throughout the day. School lunch menus
will be used to improve detailed recording about meals eaten away from home.
Participants will be prompted to include snacks. The interviewer will be
instructed to convey neutrality about reported food intake, so as not to
discourage reporting of "unhealthy" or "forbidden" foods.
The data will be summarized as total caloric intake (kcal/day) and percent of
kcal from carbohydrate, fat (total and saturated), and protein (total and
animal). Because under-reporting of food intake increases with the age of the
child, baseline dietary data will be used for longitudinal analyses.
Physical activity
before, during, and after school, will be estimated using a checklist. The checklist
asks about activities during the previous day, and includes time spent watching
television, videos or a computer screen. Responses will be weighted for level
of intensity based on standard energy intensity estimates. This checklist has
been validated as a measure of moderate to vigorous physical activity using
heart rate (r = 0.5) and accelerometer (r = 0.3) data. Parental estimates of
television viewing have been validated using videotaped observation, and have
been shown to have good test-retest reliability among children. Both the child
and a parent will be asked to complete these questionnaires, and the data
analyzed separately. While physical activity assessment in children is
challenging, physical activity estimates based on these questions have been
associated with overweight status and improvements in BMI and fitness following
an educational intervention. These data will be summarized as: a) minutes of
sedentary activity; b) minutes of moderate to vigorous physical activity; and
c) metabolic equivalents (METs) of moderate to vigorous physical activity,
where 1 MET is equivalent to the resting metabolic rate. Fasting blood
levels
Plasma immunoreactive insulin, proinsulin, C-peptide,
glucose, hemoglobin Alc (HbAlc), cholesterol, triglycerides, HDL cholesterol,
LDL cholesterol, LDL size, hematocrit, testosterone (boys), estradiol (girls),
dihydroepiandosterone sulfate (RHEA-S), insulin growth factor (IGF-1), insulin
growth factor binding protein (IGFBP-3), plasminogen activator inhibitor-1 (PAI-1),
fibrinogen, and C-reactive protein will be measured following a 10-hour
overnight fast. A blood sample will be centrifuged on-site at the GCRC .-
measure hematocrit and ensure that children are not anemic prior to obtaining
further blood samples. White blood cells from all blood samples will be pooled
and saved for their DNA. DNA samples will be used in future studies to examine
gene markers that are identified as being associated with diabetes and
cardiovascular disease. All participants will be given the option of deciding
whether to have DNA samples saved without precluding their participation in
this study.
Intravenous
glucose tolerance test (IVGTT).
Following an overnight
10-hour fast, 25% glucose (0.5g per kg body weight, to a maximum of 35g) will be
administered intravenously over 3 minutes. Prior to administration of glucose,
baseline blood samples will be drawn at 20 minutes after intravenous cannula
placement, and again in 5 minutes (immediately before glucose administration)
for measurement of plasma glucose and insulin. Samples for plasma glucose and
insulin will be drawn at 0, 1, 2, 3, 4, 5, 7, 10, 15, 20, 30 and 40 minutes
following the glucose infusion. This protocol was selected because it is widely
used and well tolerated in young children, including in the DPT-1 study. The
glucose disappearance constant (Ko, the natural logarithm of the rate of fall
in glucose between 10 and 30 minutes) provides an assessment of glucose
metabolism dependent upon a combination of insulin sensitivity and secretion.
Magnetic resonance (MR) imaging will be used
to measure subcutaneous and intra-abdominal fat at the level between the fourth
and fifth lumbar vertebra (L4-5). While MR is relatively expensive,
intra-abdominal fat is an important component of the insulin resistance
syndrome (see section B2b). Unlike computed tomography, MR does not generate
radiation exposure, which is an important consideration in pediatric subjects.
Attempts to estimate intra-abdominal fat from anthropometric measures have
shown unacceptable accuracy in children. A single observer will obtain all
measurements throughout the study to improve accuracy. MR will be performed at
the University of Washington Medical Center.
Total Volume of Blood to be Drawn: The total volume of blood drawn per year will
not exceed 45 cc. This is considerable less than 2.5% of blood volume for an 8
year old child of average weight (25 kg.), estimated to be 55cc.
1. Explain
(a) how study procedures differ from standard care and (b) whether this study
will preclude or delay standard care.
These are healthy children. All procedures are being performed solely for
the purpose of research. Normally, none of these procedures would be done on
healthy children.
2.
If any deception (withholding of
complete Information) is required for the validity of this activity, explain
why this is necessary and attach a debriefing statement.
No deception will be used.
3. Location where procedures
will be carried out.
University of Washington Medical
Center, Seattle, WA
University of Washington General Clinical Research Clinic Satellite at
Children's Hospital & Regional Medical Center, Seattle, WA
4. What CHRMC resources will be required, e.g., equipment, space,
nursing staff, pharmacy, laboratories, medical records? CRC space and personnel
Endocrinology study coordinator time.
5. How will the
CHRMC resources be funded?
NIH
Grant
6. Will subjects be
charged for any study procedures? [X] No [ ] Yes, explain.
G. RISKS AND BENEFITS. The IRB will use this information
to determine whether the benefits outweigh the risks.
1. Nature and amount of risk from all study
procedures, drugs, devices, interviews, and questionnaires. As applicable,
include physical risks (such as side effects from drugs), psychological risks
(such as substantial stress, discomfort, or invasion of privacy), and social
risks (such as jeopardy to insurability or employability).
Serious
potential risks from this study are extremely unlikely. Risks include
discomfort, ecchymoses, or inflammation from venipunctures. An experienced
pediatric nurse will place the intravenous catheter (IV) and blood will be
drawn through the IV to minimize these risks. Entertainment (such as electronic
games, television, and videos) will be available to distract children during
venipunctures. There is also risk of pain and inflammation if glucose is
injected extravascularly. While examination for sexual maturity is essential to
interpretation of the study results, efforts will be made to minimize embarrassment.
Children may choose to be examined in the presence of their parents, and all
exams will be performed by an experienced clinician with a chaperone present.
Moreover, since assessment of sexual maturation is a standard component of a
routine pediatric examination, most children will already be familiar with this
procedure. The radiation exposure associated with DXA is less than 0.1 microGy
(10 mrem) which is at the lower end of the exposure range for diagnostic
radiographs. This represents about 3°% of the average annual exposure from
natural background radiation in the United States. Magnetic resonance imaging
does not involve radiation exposure. No investigational drugs will be used.
2. Describe the expected
benefits for the Individual subjects and/or society.
There will be an educational benefit to all
children and their parents regarding lifestyle and health. Children and their
parents will have the opportunity to ask physicians, nurses, and registered
dietitians questions about nutrition, obesity, physical activity, and diabetes
risk. While most children are expected to be healthy, a beneficial effect on
the medical care of some children (e.g. those with hyperlipidemia or
hypertension) is possible. All participants may derive future benefit from the
increased knowledge about type 2 diabetes and associated conditions expected to
be gained from this study.
Currently
more than 20% of children in the United States are obese, and the numbers are
increasing. There is evidence that obesity-related diseases such as diabetes,
which until 10 years ago were seen almost exclusively in middle-aged adults,
are now affecting children. Complications, such as limb amputation, blindness,
and kidney failure are related to duration of disease. Therefore, the younger
the age of onset, the greater the chance of serious complications or premature
death. Furthermore, there is evidence that Asians are affected
disproportionately by the health consequences of excess weight, even at
relatively low degrees of overweight. Thus, there is substantial potential
benefit to society as a whole to increase our knowledge about weight gain,
metabolic changes, and risks of type 2 diabetes in children so that better
treatment options can ultimately be developed. We acknowledge that there are
significant risks of discomfort to participants in this study, although there
is negligible risk of serious harm. We feel that by taking precautions to
minimize discomfort, ensuring as pleasant an experience as possible for the
participants, and providing children and their parents information about this
public health problem, that the benefits to society will clearly be outweighed
by the risks.
H. FOLLOW-UP planned at completion of study, e.g., return
of information to subjects, referral to appropriate practitioners. Explain what
information families will receive at what point in the research, and who will
convey the information to families.
Results
which may be relevant to the participant's medical care (e.g. height, weight,
blood pressure, hematocrit, glucose, cholesterol, LDL cholesterol, HDL
cholesterol and triglycerides) will be sent by mail to the child and consenting
parent. If the parent provided written consent at the time of the visit, these
results will also be provided to the child's physician. All other study
information, including genetic information, will be completely confidential and
will be used for research purposes only.
1. Are results likely to have diagnostic, predictive, or reproductive
implications? [ ] No [X] Yes, explain
It is
possible that a small number of children will be found to have elevated blood
pressure, blood sugar, or cholesterol. As described above, clinically relevant
information will be sent to the child and their parent. These results will be
noted as normal or abnormal. If abnormal, we will provide written instructions
to contact their regular physician for further evaluation. If this were to
occur, it would likely be beneficial to the child, since these potentially
treatable conditions may otherwise have gone undetected.
There
is an extremely low likelihood that one of our research-oriented measures could
indicate a serious medical condition. For instance the DHEA-S level, which is
being used to validate pubertal stage, could be extremely high, suggesting a
tumor. Likewise, the MRI, being used to measure intra-abdominal fat, could show
an
abnormal mass. In this event,
we will contact the child's parent and inform them of the result, and recommend
evaluation by the child's regular physician. We will also request permission
from the child's parent to notify the child's physician of these findings. If
this were to occur, it could actually be of benefit to the child, since the
research protocol may have detected a serious condition at an early and curable
stage.
2. If applicable, explain how interim or inconclusive results will be
handled and whether subjects will be given the opportunity not to receive
information about themselves.
There are no interim results. Clinically relevant results will be
sent with an interpretation as to whether the results are normal, abnormal, or
borderline. In the unlikely event that participants do not wish to receive
results, none will be sent. This has not happened with any of our previous
participants.
Please see page 10, section J 5(c) regarding stored DNA
samples.
I. ADVERSE EFFECTS
1. How and by whom will adverse
effects be handled?
[X] By investigators [X] Referred for appropriate care [ ]
Other, explain.
2. Are facilities adequate for handling adverse
effects? [X] Yes[ ] No, explain
3. Who will be financially
responsible for treatment of adverse effects resulting from study procedures? [ ]
Study sponsor [ ] Subject [X] UW compensation plan [
]Other, explain
J. CONFIDENTIALITY
1. Will study datalsamples be
anonymous (no possible link to identifiers)? [ ]
Yes [X]
No
2. Will
data/samples be confidential (identifiable with a unique study code) and will
the key to the code be kept separate from the data/samples? [X] Yes [ ]
No If "No," explain.
3. Will any other agency or non-study personnel
have access to identifiable
[ ] Yes
[X] No data/samples? If "Yes," specify and explain.
4.
What provisions will be made for controlling access to the data/samples?
[X] Computer with restricted
access [X] locked
file [ ] Other, explain
Data will be coded. A master
list linking data to individual subjects will be securely maintained separately
from the data in locked filing cabinet and in a password protected computer
file. The computer file will be necessary so that we can send out letters to
participants reminding them of follow-up; it will contain study id number,
patient name and address. Direct identifiers
will be removed from paper data collection forms as soon as data collection
is complete, and the data has been entered. Computer files of data results will
not contain direct identifiers.
This is a longitudinal study which requires that we retain the ability
to contact participants for future followup. The initial funding period we are
requesting is for 5 years, but we plan to renew the grant for future follow-up.
The direct identifier link will destroyed if no additional funding to continue
the study has been obtained for 15 consecutive years after the most recent data
collection.
5. Does this study involve
long-term storage or "banking" of the datalsamples?
[X] Yes [ ] No
If "Yes," explain how the banked data/samples
will be handled:
(a) If a subject wishes to withdraw
from a study after It has begun or after it has been completed.
Subjects may withdraw at any time by notifying any of the
investigators listed on the consent form.
(b) If another investigator
wishes to use the banked data/samples for the same research purposes.
Data and samples may be used only if in collaboration
with one of the original investigators.
(c) If either you or another
investigator wish to use the banked data/samples for different research
purposes.
Use of
banked data or samples for unrelated research purposes will not be permitted
without reconsenting the participants.
Note that we do plan to bank
DNA for future analysis. The research purpose will be the same as for this
study. Children and parents will be advised at the time of consent that DNA
will be saved for analysis in future studies, and all participants will have
the option of declining to have DNA samples saved. These future studies will
involve looking to see whether specific genes or gene markers related to
glucose or fat metabolism, diabetes, or cardiovascular
disease are related to other metabolic markers of diabetes risk in our study.
Thus these future studies are related to the original research purposes. It is
hoped that this information will improve our understanding of the
pathophysiology of the insulin resistance syndrome so that better treatments
can be developed. It is highly unlikely that this information will be
clinically relevant to an individual child, as no diagnostic DNA tests
currently exist for type 2 diabetes or cardiovascular disease. Furthermore, the
DNA analysis will be performed in a research lab, not a clinical lab. It will
not be possible for the lab performing this analysis to directly link the
results of the DNA analysis to a specific individual by name, as the samples
will be coded by study ID number only. We will explain that use of this
information is for research purposes only, and results will not be shared with
study subjects, their parents or their physician. We will submit an addendum
Human Subjects Application at which time these samples are ready to be
analyzed, providing information about the specific tests to be performed, and
including details about where the samples will be run. DNA samples will be
labeled by study ID only, and will not be labeled with direct identifiers. DNA will be stored in the laboratory of Dr.
Wilfred Fujimoto until ready for processing.
VII. CHECKLIST FOR INVESTIGATORS:
A. Will any group, agency, or organization be involved? [ ] Yes [X] No If yes, explain:
B. RADIATION. Will materials with potential
radiation risk be used, e.g. x-rays,
radiopharmaceuticals, radiation therapy? [X] Yes [ ] No
If "Yes:" DEXA
1. Is this use investigational, experimental, or
with greater frequency or Intensity so that it might be considered a departure
from the standard care for the patient's condition?
[X] Yes [
] No [ ] Don't know
If the answer
is "Yes" or "Don't know," the project will require review
by the Radiation Safety Committee. Submit a copy of the IRS application and a cover
letter explaining the use of radioactive materials to David Rosenbaum, MD,
Radiology, CH-69.
2. Has project been approved by the Radiation Safety Committee? [ ] Yes [X] Pending
Submitted to UW Radiation Safety Commitee, as testing with radiation to
be done at UW.
C. BLOOD DRAWS. The chart below represents average blood volume for the
ages specified,
premature
infants through 2 years.
|
Age |
Total |
2 1/2% |
|
|
Blood Volume |
Volume |
|
26 wk |
104 ml |
3
ml |
|
30 wk |
158 ml |
4
ml |
|
34 wk |
242 ml |
6
ml |
|
Term |
340 ml |
9
ml |
|
3 mos |
500 ml |
13
ml |
|
6 mos |
670 ml |
17
ml |
|
9 mos |
800 ml |
20
ml |
|
12 mos |
900 ml |
23
ml |
|
24 mos |
1100 ml |
28
ml |
1. Will blood be withdrawn for research purposes in an
amount greater than 2 1/2% for a single draw or 5%. within a two-month period?
If "Yes," explain why this is necessary and comment on associated
risks. [ ]
Yes [X] No
The total volume of blood drawn
per year will not exceed 45 cc. This is considerable less than 2.5% of blood
volume for an 8 year old child of average weight (25 kg.), estimated to be 55
cc.
2. Are combined draws for clinical and
research purposes likely to exceed these amounts? [ ] Yes
[X]No If "Yes,"
comment on associated risks.
D. DRUGS AND
OTHER SUBSTANCES.
1. Will an Investigational new drug (IND) or
other investigational substance be used in the study? [ ] Yes [X] No If "Yes," provide the
following information about each drug/substance: (Add sheets if necessary.)
|
Name |
Dosage |
Route of Administration |
Phase of Testing |
IND# |
Side Effects |
|
|
Generic |
Trade |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
For each IND,
provide one copy of the drug Protocol and of the following information:
• toxicity data
• reports of animal
studies
• reports of human
studies in adults and children
NOTE: For sponsored studies, the bulleted
information is usually contained in the "Investigator's Brochure" written
by the sponsor. If the study is not sponsored or if there is no
"Investigator's Brochure," prepare a brief summary of this
information for the Board and, if available, attach relevant articles.
[ ] Yes
[ ] No, explain
3. Will other drugs or substances be used? [X] Yes [ ] No If "Yes," provide the following
information about each drug/substance: (Add sheets if necessary.)
|
Name |
Dosage |
Route of Administration |
Side Effects |
|
|
Generic |
Trade |
|
|
|
|
glucose 25% |
various |
0.5k9
body wt. |
intravenous catheter |
|
|
|
|
(max of 35) |
|
|
|
|
|
|
|
|
For each drug specify:
a. Has the drug/substance been labeled for use
with children in the proposed age group? [X] Yes[ ] No
b. Has the drug/substance been labeled for
this use? [X] Yes
[ ]
No
c. Has the drug/substance been approved in
this form? [X] Yes
[ ] No
NOTE: If the answer to a., b.,
or c. Is "No," the drug or substance you wish to study may be
considered investigational, requiring an IND number from the FDA. Call Research
Administration (526-2139 or 526-2023) for more information.
E. DEVICES.
Will an investigational device be used? [ ] Yes [X] No
NOTE: If "Yes," provide name, source,
description, how used, and FDA's investigational device exemption (IDE) number.
If there is no IDE, explain and include a statement as to why the device
qualifies as a non-significant risk device. Attach one copy of the protocol,
descriptions of studies in animals and humans, and drawings or photographs of
the device.
F. OTHER INFORMATION
1. Will medical or academic
records be used? (circle or indicate which) If "Yes", explain which
records will be used: Yes [X] No
2. Will
written consent form(s) be used? [X] Yes
[ ] No Written consent is
required in most cases (in addition to an oral explanation). If
"No," explain why a written consent form will not be used.
A NOTE ABOUT
CONSENT FORMS:
LAY LANGUAGE The language and syntax of the consent
form should be directed to the lay reader at the 6th grade level. Scientific or
medical terminology should be defined within the document itself, or avoided
when possible. Even those parents who use medical terms in conversation may not
understand their meaning.
FORMAT.
The CHRMC IRB prefers that consent forms adhere to a standard format as shown
in the sample form on pages 11-13. Whether this or another format is used, the
Investigator is responsible for including all necessary information as required
by the federal regulations, as well as additional information required by the
Board. (This information is included as a checklist in the sample form .)
SIGNATURES. Federal
regulations require that consent be obtained from both parents unless: (a) the
research involves no greater than minimal risk; or (b) the research involves
greater than minimal risk but presents the prospect of direct benefit to the
child; or (c) one parent is deceased, unknown, incompetent, or not reasonably
available, or when only one parent has legal responsibility for the care and
custody of the child.
3. Will assent
be obtained?[X]
Yes [ ] No If "No," explain why assent will not be obtained.
A NOTE ABOUT ASSENT FORMS
REQUIREMENT
FOR ASSENT. Assent (either written or oral) is required in most cases unless:
(a) the child is incapable of understanding the research Intervention; or (b)
the research intervention holds out the prospect of direct benefit to the child
which is available only within the context of the research. (For drug studies,
this means that assent is usually required in studies that include
randomization to placebo.)
WRITTEN ASSENT is required from children 7 years or older
who are able to read and understand the research intervention. Children age 12
years and older may indicate assent by co-signing the consent form for their
parents. A simplified written assent form is required for children age 7•11.
ORAL
ASSENT is required from children younger than 7 who are old enough to
understand the research Intervention.
LANGUAGE
AND CONTENT. The language and syntax of the assent form must be geared to the
cognitive level of the children being asked to participate. Procedures or
aspects of procedures which are part of the study but not part of the child's
care must be clearly described as optional. Any information that will affect
the child's decision should be included, e.g., the involvement of to the
child's teacher to provide behavioral information or of playmates to serve as
control subjects. Samples of oral and written assent documents are included on
page 14.