Clinical trial NCT02516657
Conditions: Type 1 Diabetes
Sponsor: University at Buffalo
Start date: 2012-05-01; Completion date: 2023-08-03
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to study the effect of a liraglutide, a glucagon-like peptide agonist, on post-meal blood glucose concentrations, glucagon levels, mean weekly blood sugars, and insulin doses in adolescents with Type 1 diabetes. Type 1 diabetes is an autoimmune disease that is usually diagnosed before the age of 20. Individuals with this disease are completely dependent on insulin for survival. While significant advances have been made in technological support for improving diabetes control, insulin remains the only effective treatment for Type 1 diabetes. Liraglutide is a long-acting glucagon-like peptide-1 analog. This drug is approved for the treatment of Type 2 diabetes in adults. This study will test the effect of liraglutide on blood sugar control in adolescents with Type 1 diabetes.

Detailed description:
Type 1 diabetes (T1DM) affects approximately 1:500 children and represents the major form of diabetes in the pediatric population (1). Diagnosis of T1DM is based on symptoms consistent with hyperglycemia (polyuria, polydipsia, and weight loss) and elevated blood sugars. Diagnosis of T1DM is confirmed by measuring serum autoantibodies against insulin and other beta-cell proteins. Subcutaneous insulin is the mainstay of diabetes care; however, ability to achieve optimal glycemic control is impacted by multiple factors including diet, exercise, and psychosocial barriers.

The Diabetes Control and Complications Trial and follow-up EDIC trial were landmark studies demonstrating that improving glycemic control significantly reduces the risk of both micro and macro-vascular disease (2). While technologic advances in blood sugar monitoring, insulin analogs and insulin delivery devices have been made, it is estimated that less than 40% of individuals meet recommended glycemic standards as set forth by the American Diabetes Association; these estimates may be lower in the pediatric population. Thus, adjuvant pharmacologic therapies that improve glycemic control are being tested in patients with T1DM.

Incretin hormones are a class of intestinal peptides that are released in response to nutrient intake (3). The best described incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones act at the level of direct stimulation of pancreatic β-cell function and through extra-pancreatic mechanisms. They primarily potentiate glucose-dependent insulin secretion from the β-cell; other β-cell effects include increasing insulin biosynthesis, stimulating β-cell replication, and preventing apoptosis. Secondary effects of incretin hormones include suppression of glucagon secretion, inhibition of gastric emptying, and potentiation of hepatic glucose uptake (3).

Currently, there are two GLP-1 analogs approved by the Food and Drug Adminstration as adjuvant treatment of Type 2 diabetes mellitus in adults (\> 18 years) who fail to reach glycemic targets with metformin and/or oral hypoglycemic agents. The two drugs - exenatide (BID) and liraglutide (QD) are administered subcutaneously. They have been demonstrated to improve glycemic control in this population and, in some individuals, lead to sustained weight loss.

This study aims to determine whether acute exposure to liraglutide decreases the mean weekly blood glucose levels in adolescents with T1DM. In addition, we will determine whether liraglutide decreases glucose excursions following a meal challenge. The overall hypothesis to be tested is that short-term exposure (7 days) to liraglutide improves glycemic control in adolescents/young adults with T1DM treated with continuous subcutaneous insulin infusion.

Arms: arm 1: Liraglutide 0.6 mg daily injection x 7 days
Interventions: intervention 1: Liraglutide
Intervention descriptions: intervention 1: Liraglutide 0.6 mg

Protocol documents:
Prot_SAP_000.pdf: 
 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
 
PROTOCOL TITLE: Effect of liraglutide on glycemic control, glucagon secretion 
and inflammatory markers in adolescents with Type 1 diabetes mellitus. 
Page 1 of 32 
 
Official Title:
Liraglutide in Adolescents with Type 1 Diabetes 
NCT number: 
02516657 
Document Type: 
Study Protocol 
Date of the 
Document: 
August 15, 2019 
 
 
 


 
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Revised: July 24, 2018 
 
INSTRUCTIONS: Complete Research Protocol (HRP-503) 
 Depending on the nature of what you are doing, some sections may 
not be applicable to your research.  If so, you must provide the 
reason why the section is not applicable for the response.  For 
example, most behavioral studies would answer all questions in 
section 30 with words to the effect of “drugs and medical devices 
are not used in this study.” 
 When you write a protocol, keep an electronic copy. You will need 
to modify this copy when making changes. 
 Do not remove the italics instructions or headings. 
 If you are pasting information from other documents be sure to use 
the “Merge Formatting” paste option so that the formatting of the 
response boxes is not lost.  If information is presented outside of 
the response boxes, it will not be accepted.  
 If this study involves multiple participant groups who participate 
in different research procedures, consent processes, etc., be 
certain to provide information in each applicable section for each 
participant group and clearly label each participant group within 
a section or subsection.  
 
 
PROTOCOL TITLE: 
Response: Effect of liraglutide on glycemic control, glucagon secretion and 
inflammatory markers in adolescents with Type 1 diabetes mellitus. 
 
PRINCIPAL INVESTIGATOR: 
Name: Lucy D. Mastrandrea, MD, PhD 
Department: Pediatrics 
Telephone Number: 716-323-0170 
Email Address: lmastrandrea@upa.chob.edu 
 
VERSION NUMBER: 
Include the version number of this protocol. 
Response: 3 
 
DATE: 
Include the date of submission or revision. 
Response: August 15, 2019 


 
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Revised: July 24, 2018 
 
Grant Applicability: 
Describe whether or not this protocol is funded by a grant or contract and if so, 
what portions of the grant this study covers. 
Response: N/A 
 
 


 
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Revised: July 24, 2018 
Table of Contents 
1.0 
Objectives ................................................................................................................ 5 
2.0 
Background .............................................................................................................. 5 
3.0 
Inclusion and Exclusion Criteria .............................................................................. 8 
4.0 
Study-Wide Number of Subjects (Multisite/Multicenter Only) .............................. 9 
5.0 
Study-Wide Recruitment Methods (Multisite/Multicenter Only)............................ 9 
6.0 
Multi-Site Research (Multisite/Multicenter Only)................................................. 10 
7.0 
Study Timelines ..................................................................................................... 10 
8.0 
Study Endpoints ..................................................................................................... 10 
9.0 
Procedures Involved............................................................................................... 12 
10.0 Data and Specimen Banking .................................................................................. 15 
11.0 Data Management .................................................................................................. 15 
12.0 Provisions to Monitor the Data and Ensure the Safety of Subjects ....................... 17 
13.0 Withdrawal of Subjects .......................................................................................... 18 
14.0 Risks to Subjects .................................................................................................... 18 
15.0 Potential Benefits to Subjects ................................................................................ 20 
16.0 Vulnerable Populations .......................................................................................... 21 
17.0 Community-Based Participatory Research ............................................................ 22 
18.0 Sharing of Results with Subjects ........................................................................... 22 
19.0 Setting .................................................................................................................... 22 
20.0 Resources Available............................................................................................... 23 
21.0 Prior Approvals ...................................................................................................... 24 
22.0 Recruitment Methods ............................................................................................. 24 
23.0 Local Number of Subjects ..................................................................................... 25 
24.0 Confidentiality ....................................................................................................... 25 
25.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 26 
26.0 Compensation for Research-Related Injury ........................................................... 26 
27.0 Economic Burden to Subjects ................................................................................ 27 
28.0 Consent Process ..................................................................................................... 27 
29.0 Process to Document Consent in Writing .............................................................. 31 
30.0 Drugs or Devices.................................................................................................... 31 
 


 
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Revised: July 24, 2018 
1.0 
Objectives 
1.1 Describe the purpose, specific aims, or objectives. 
Response: Type 1 diabetes is one of the most common chronic diseases of childhood.  
It is caused by autoimmune destruction of the insulin-producing pancreatic beta cells.  
Patients with Type 1 diabetes are at high risk for development of long-term complications 
related to hyperglycemia.  Individuals with this disease are completely dependent on 
insulin for survival.  While significant advances have been made in technological support 
for improving diabetes control, insulin remains the only effective treatment for Type 1 
diabetes.  
1.2 State the hypotheses to be tested. 
Response: The main objective of this study is to test the hypothesis that a long-
acting glucagon-like peptide 1 analog, liraglutide, will improve mean weekly blood 
sugars in adolescents and young adults with Type 1 diabetes.   
Background 
1.3 Describe the relevant prior experience and gaps in current 
knowledge. 
Response: Background:  Type 1 diabetes (T1DM) affects approximately 1:500 children 
and represents the major form of diabetes in the pediatric population (1).  Diagnosis of 
T1DM is based on symptoms consistent with hyperglycemia (polyuria, polydipsia, and 
weight loss) and elevated blood sugars.  Diagnosis of T1DM is confirmed by measuring 
serum autoantibodies against insulin and other beta-cell proteins.  Subcutaneous insulin is 
the mainstay of diabetes care; however, ability to achieve optimal glycemic control is 
impacted by multiple factors including diet, exercise, and psychosocial barriers.   
The Diabetes Control and Complications Trial and follow-up EDIC trial were 
landmark studies demonstrating that improving glycemic control significantly reduces the 
risk of both micro and macro-vascular disease (2).  While technologic advances in blood 
sugar monitoring, insulin analogs and insulin delivery devices have been made, it is 
estimated that less than 40% of individuals meet recommended glycemic standards as set 
forth by the American Diabetes Association; these estimates may be lower in the 
pediatric population.  Thus, adjuvant pharmacologic therapies that improve glycemic 
control are being tested in patients with T1DM. 
Incretin hormones are a class of intestinal peptides that are released in response to 
nutrient intake (3). The best described incretin hormones are glucagon-like peptide-1 
(GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).  These hormones act at 
the level of direct stimulation of pancreatic β-cell function and through extra-pancreatic 
mechanisms.  They primarily potentiate glucose-dependent insulin secretion from the β-
cell; other β-cell effects include increasing insulin biosynthesis, stimulating β-cell 
replication, and preventing apoptosis.   Secondary effects of incretin hormones include 
suppression of glucagon secretion, inhibition of gastric emptying, and potentiation of 
hepatic glucose uptake (3).  
Currently, there are two GLP-1 analogs approved by the Food and Drug 
Adminstration as adjuvant treatment of Type 2 diabetes mellitus in adults (> 18 years) 
who fail to reach glycemic targets with metformin and/or oral hypoglycemic agents.  The 


 
Page 6 of 32 
Revised: July 24, 2018 
two drugs – exenatide (BID) and liraglutide (QD) are administered subcutaneously.  They 
have been demonstrated to improve glycemic control in this population and, in some 
individuals, lead to sustained weight loss.  
This study aims to determine whether acute exposure to liraglutide decreases the 
mean weekly blood glucose levels in adolescents with T1DM.  In addition, we will 
determine whether liraglutide decreases glucose excursions following a meal challenge.  
The overall hypothesis to be tested is that short-term exposure (7 days) to liraglutide 
improves glycemic control in adolescents/young adults with T1DM treated with 
continuous subcutaneous insulin infusion.  
Specific Aim 1: Determine whether liraglutide decreases the mean weekly blood glucose 
levels in adolescents/young adults with T1DM.   Hypothesis: Mean weekly blood glucose 
will decrease when liraglutide is used as an adjuvant therapy to insulin in individuals 
with T1DM.  Subjects will wear continuous glucose monitors to measure interstitial 
glucose as a surrogate for blood glucose.  The CGM will be worn for 7 days pre- and 
post- daily liraglutide treatment.  Data will be downloaded and mean weekly blood sugars 
will be determined.  
Specific Aim 2: Determine whether liraglutide treatment decreases blood glucose 
excursion during mixed meal tolerance test in adolescents/young adults with T1DM.  
Hypothesis: Post-prandial blood glucose excursions are attenuated with liraglutide 
treatment.  Mixed meal tolerance tests will be performed with and without pre-treatment 
with liraglutide.  Blood glucose levels will be measured at set time points during the test 
and blood glucose excursions as well as blood glucose AUC in response to the meal 
challenge will be calculated.     
Specific Aim 3:  Determine whether glucagon secretion decreases during mixed meal 
tolerance test in subjects treated with liraglutide.  Hypothesis:  Glucagon secretion 
following a meal challenge is suppressed in response to liraglutide treatment.  Serum 
samples will drawn during mixed meal tolerance test performed with and without pre-
treatment with liraglutide.  Glucagon will be measured by ELISA and glucagon secretion 
AUC will be calculated.   
Specific Aim 4:  Determine whether liraglutide treatment leads to a reduction in total 
daily insulin dose.  
Hypothesis:  Improved glycemic control can be attained with lower total daily insulin 
requirements in subjects treated with liraglutide.  Total daily insulin dose will be 
determined for seven days before and after initiation of liraglutide therapy.  Insulin 
dose/kilogram body weight will be determined and evaluated in relationship to changes in 
mean weekly blood sugars. 
In addition to the specific aims outlined above, the following exploratory aims will be 
addressed: 
Exploratory Aim 1:  Determine the side effect profile of liraglutide in adolescents/young 
adults with T1DM.  Hypothesis:  Side effect profile of short-term liraglutide treatment in 
this population will be similar to that reported in adults.  Study subjects will keep a diary 
reporting hypoglycemic events and other potential adverse effects. Type, number, and 
rate of adverse events will be determined. 


 
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Revised: July 24, 2018 
Exploratory Aim 2:  Determine if there is a difference in caloric intake with liraglutide 
treatment in adolescents/young adults with T1DM.  Hypothesis:  Caloric intake 
decreases in response to liraglutide treatment.  Subjects will keep a 4 day food record 
before and after initiation of liraglutide.  Total caloric intake will be calculated, and 
within subject differences in caloric intake before and after liraglutide treatment will be 
determined. 
Exploratory Aim 3:  Determine if liraglutide treatment alters serum inflammatory 
markers in subjects with T1DM.  Hypothesis: Acute liraglutide therapy decreases serum 
levels of C-reactive protein and increases adiponectin levels in subjects with T1DM.  
Serum samples before and after liraglutide therapy will be drawn and levels of 
inflammatory markers will be measured.  Within subject differences will be determined. 
Describe any relevant preliminary data.  
Response: Although individuals with T1DM may not benefit from the direct β-
cell actions of GLP-1 analogs given the targeted autoimmune component of the 
disease, the impact on glucagon secretion and extra-pancreatic effects may 
improve overall glycemic control in this population.  At least two studies have 
reported data testing the efficacy of GLP-1 analogs in individuals with T1DM.  
Heptulla et al. reported significant reductions in glucose excursions following a 
standard meal test in adolescents and young adults (n = 8, age 13-22) treated with 
a single dose of exenatide (4).  Varanasi et al. reported that mean weekly glucose 
levels decreased significantly in adults with well-controlled T1DM (mean HbA1c 
= 6.4%) treated with daily liraglutide for 1 week (5). These findings suggest that 
GLP-1 analogs may represent potential therapeutic adjuvants to improve glycemic 
control in patients with T1DM. 
1.4 Provide the scientific or scholarly background for, rationale for, and 
significance of the research based on the existing literature and how 
will it add to existing knowledge. 
Response: Optimal diabetes control decreases the risk of long-term micro- and 
macro vascular complications in individuals with diabetes.  Currently the only 
FDA approved therapy for management of T1DM is insulin, delivered either 
subcutaneously or via inhalation.  The addition of therapies to decrease risk of 
glucose excursions at mealtimes would offer significant benefits to diabetes care. 
1.5 Include complete specific citations/references.  
References: 
1. Bell RA, Mayer-Davis EJ, Beyer JW, D'Agostino RB, Jr., Lawrence JM, Linder B, et 
al. (2009) Diabetes in non Hispanic white youth: prevalence, incidence, and clinical 
characteristics: the SEARCH for Diabetes in Youth Study. Diabetes Care.32 Suppl 
2:S102-11. 
2. http://diabetes.niddk.nih.gov/dm/pubs/control/ 
3. Drucker DJ (2006) The biology of incretin hormones. Cell Metabolism 3:153-165. 
4. Raman VS, Mason KJ, Rodriguez LM, Hassan K, Yu X, Bomgaars L, Heptulla RA 
(2010) The role of adjunctive exenatide therapy in pediatric type 1 diabetes. Diabetes 
Care. 33: 1294-1296. 


 
Page 8 of 32 
Revised: July 24, 2018 
5. Varanasi A, Bellini N, Rawal D, Vora M, Makdissi A, Dhindsa S, Chaudhuri A, 
Dandona P (2011) Liraglutide as additional treatment in type 1 diabetes. Eur J 
Endocrin epub ahead of print. 
 
2.0 
Inclusion and Exclusion Criteria 
2.1 Describe the criteria that define who will be included or excluded in 
your final study sample.  
Characteristics of the Research Population 
 
Gender of Subjects: Male and female subjects 
 
Age of Subjects: 15 – 21 years 
 
Racial and Ethnic Origin:  All racial and ethnic groups will be included 
 
Inclusion Criteria 
o Adolescents and young adults followed by the UBMD Pediatrics, Division of 
Endocrinology/Diabetes Center. 
o Diagnosis of T1DM greater than 1 year 
o Insulin regimen – continuous subcutaneous insulin infusion with or without 
concurrent use of continuous glucose monitoring device 
o HbA1c <10% 
 
Exclusion Criteria 
o Previous exposure to liraglutide 
o History of abdominal surgery 
o Gastrointestinal reflux disease 
o History of acute or chronic pancreatitis 
o History of alcohol abuse or unwillingness to abstain from alcohol during the 
study 
o Unwilling to wear a continuous glucose monitoring device during the study. 
o History of thyroid cancer 
o Family history of Multiple Endocrine Neoplasia 2B syndrome 
o Pregnant/breastfeeding females 
o Individuals with antibody-negative insulin requiring diabetes that is 
consistent with Monogenic Diabetes of Youth 
o Individuals with steroid induced or cystic fibrosis related diabetes. 
o Non-English speaking subjects 
2.2 Describe how individuals will be screened for eligibility. 
Response:  
Recruitment:  Subjects will be recruited from the UBMD Pediatrics, Division of 
Endocrinology/Diabetes clinic.  
2.3 Indicate specifically whether you will include or exclude each of the 
following special populations: (You may not include members of 
these populations as subjects in your research unless you indicate 
this in your inclusion criteria.) 
 
Adults unable to consent 
 
Individuals who are not yet adults (infants, children, teenagers) 
 
Pregnant women 
 
Prisoners 


 
Page 9 of 32 
Revised: July 24, 2018 
Response: N/A 
2.4 Indicate whether you will include non-English speaking individuals.  
Provide justification if you will exclude non-English speaking 
individuals.  
(In order to meet one of the primary ethical principles of equitable 
selection of subjects, non-English speaking individuals may not be 
routinely excluded from research.  In cases where the research is of 
therapeutic intent or is designed to investigate areas that would 
necessarily require certain populations who may not speak English, 
the researcher is required to make efforts to recruit and include non-
English speaking individuals.  However, there are studies in which it 
would be reasonable to limit subjects to those who speak English: 
e.g., pilot studies, small unfunded studies with validated instruments 
not available in other languages, numerous questionnaires, and 
some non-therapeutic studies which offer no direct benefit.)  
 
Response: We will not be including non-English speaking individuals in 
this study for the following reasons 1) pilot study; 2) unfunded  
 
3.0 
Study-Wide Number of Subjects (Multisite/Multicenter Only) 
3.1 If this is a multicenter study, indicate the total number of subjects to 
be accrued across all sites. 
Response: N/A 
 
4.0 
Study-Wide Recruitment Methods (Multisite/Multicenter Only) 
If this is a multicenter study and subjects will be recruited by methods not under 
the control of the local site (e.g., call centers, national advertisements) describe 
those methods.  Local recruitment methods are described later in the protocol. 
4.1 Describe when, where, and how potential subjects will be recruited. 
Response: N/A 
4.2 Describe the methods that will be used to identify potential subjects. 
Response: N/A 
4.3 Describe materials that will be used to recruit subjects. (Attach 
copies of these documents with the application. For advertisements, 
attach the final copy of printed advertisements. When advertisements 
are taped for broadcast, attach the final audio/video tape. You may 
submit the wording of the advertisement prior to taping to preclude 
re-taping because of inappropriate wording, provided the IRB 
reviews the final audio/video tape.) 
Response: N/A 


 
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5.0 
Multi-Site Research (Multisite/Multicenter Only) 
5.1 If this is a multi-site study where you are the lead investigator, 
describe the processes to ensure communication among sites, such 
as: 
 
All sites have the most current version of the protocol, consent 
document, and HIPAA authorization. 
 
All required approvals have been obtained at each site 
(including approval by the site’s IRB of record). 
 
All modifications have been communicated to sites, and 
approved (including approval by the site’s IRB of record) 
before the modification is implemented. 
 
All engaged participating sites will safeguard data as required 
by local information security policies. 
 
All local site investigators conduct the study appropriately. 
 
All non-compliance with the study protocol or applicable 
requirements will reported in accordance with local policy. 
Response: N/A 
5.2 Describe the method for communicating to engaged participating 
sites: 
 
Problems. 
 
Interim results. 
 
The closure of a study 
Response: N/A 
6.0 
Study Timelines 
6.1 Describe the duration of an individual subject’s participation in the 
study. 
Response: The total duration of time for participation is 2 weeks. This 
study involves three visits. 
6.2 Describe the duration anticipated to enroll all study subjects. 
Response: 4 years 
6.3 Describe the estimated date for the investigators to complete this 
study (complete primary analyses) 
Response: 60 months 
7.0 
Study Endpoints 
7.1 Describe the primary and secondary study endpoints. 
Response: For statistical purposes, the primary endpoint of the study is to detect 
a difference between untreated and treated periods in the change from baseline in mean 
weekly blood glucose concentrations. The statistical analysis will be carried out using 


 
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analysis of variance (ANOVA) and tested at the 0.05 level. The results will be computed 
as mean±SD. 
The secondary end points based on glycemic changes will include the difference 
from baseline in standard deviations of the mean weekly glucose concentrations, mean 
fasting blood glucose concentrations, the duration of time spent in hyperglycemia 
(>150mg/dl, > 200mg/dl, > 250mg/dl) and hypoglycemia (< 70mg/dl, < 40mg/dl), and 
insulin dosage. A reduction in the area under curve following the meal will constitute 
another secondary end point. Within subject comparisons of the magnitude of change 
from baseline will also be made for these glycemia related secondary endpoints using 
student’s t-test. Comparisons for these and the primary endpoints will also be made using 
the paired t-test or Wilcoxson’s test for paired data for each subject. Additional secondary 
end-points of the study will be change from baseline in 1) mean weekly blood glucose 2) 
glucagon area under the curve concentrations following meal challenge 3) change in daily 
insulin dose (total dose and units/kg) 4) caloric intake based on 4 day food records and 5) 
change in serum adiponectin and CRP levels before and after initiation of liraglutide 
treatment. The relation between change in postprandial sugars, glucagon, and total daily 
insulin dose will be studied by regression analysis to evaluate the relative contribution of 
each of these parameters to the improvement in post-prandial blood sugars. 
Variables of Interest: 
   
Visit 1 
 Age, gender, height, weight, total daily insulin dose, HbA1c, insulin pump 
settings 
 Total daily insulin dose 
 History of severe hypoglycemic events,  
 History of pancreatitis, alcohol use, thyroid cancer, family history of MEN 
2B 
Visit 2 
 Insulin pump settings 
 Total daily insulin dose 
 Food diaries 
 Download of continuous glucose monitor – mean weekly blood sugars 
 Blood sugar records with reports of hypoglycemia 
 Mean blood glucose excursion, glucagon release, and serum inflammatory 
markers during mixed meal tolerance test 
Visit 3 
 Insulin pump settings 
 Total daily insulin dose 
 Food diaries 
 Download of continuous glucose monitor – mean weekly blood sugars 
 Blood sugar records with reports of hypoglycemia 
 Adverse effects  
 Mean blood glucose excursion, glucagon release, and serum inflammatory 
markers during mixed meal tolerance test 
Describe any primary or secondary safety endpoints. 


 
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Revised: July 24, 2018 
Response: Adverse effects including nausea/vomiting, anorexia.  Injection 
site reactions/pain.  Rates of hypoglycemia. Clinical or biochemical 
evidence of pancreatitis. 
8.0 
Procedures Involved 
8.1 Describe and explain the study design. 
Response: This is a pilot unblinded prospective within subject investigational-drug 
intervention trial. 
8.2 Provide a description of all research procedures being performed 
and when they are performed, including procedures being performed 
to monitor subjects for safety or minimize risks. 
Response: 
Summary of Research Design and Procedures: 
The proposed study will involve three visits.  The study will involve an initial 
screening meeting at which time the subject will be invited to join the study and sign 
informed consent.  During the Visit 2 and Visit 3, mixed meal tolerance tests will be 
performed. 
Visit 1 Screening Day (day 0): 
  Review the subject’s  medical history and family medical history 
  Review subject’s blood sugars and insulin pump settings 
  Measure height, weight, blood pressure and heart rate. 
  The principal investigator will perform a physical exam. 
  If hemoglobin A1c level is not recorded in the medical record within 2 weeks of visit 1, 
this test will be performed. 
 Record mean total daily insulin dose (previous 72 hours) from insulin pump. 
  Subjects will be advised to wear his/her continuous glucose monitor (CGM) for the next 
two weeks, changing sites as indicated by the manufacturer.  
 For subjects who do not have a CGM, we will insert the Abbott Freestyle Libre Profession 
Device. This device will monitor glucose levels throughout the entire study period.  
Subjects will be advised to check blood sugars at least 4 times per day and at any 
occasion when symptoms of hypoglycemia develop. 
  Subjects will be asked to keep a record of any episodes of hypoglycemia. 
  Subjects will be asked to keep a 4 day food record (three days, 1 weekend day). 
  Subjects will be advised to follow their usual diabetes care plan with respect to 
carbohydrate counting, diet and exercise.    
Visit 2 (Day 7):  Subjects will come fasting for this visit.  They will bring the food records and 
diary of hypoglycemia to this visit. This visit will take approximately 4 hours.  At this visit, the 
following procedures will be performed: 
 
Records of blood sugars and CGM data will be obtained from subjects wearing personal 
CGMs 
 
Subjects wearing the Freestyle LibrePro system will continue wearing the device unless it 
became dislodged during the study. A new device will be placed in this case. 
 
Blood sugars and insulin pump settings will be reviewed. 
 
Record mean total daily insulin dose (previous 72 hours) from insulin pump. 
 
A Mixed Meal Tolerance test will be performed (see below) 


 
Page 13 of 32 
Revised: July 24, 2018 
 
Insulin pump settings will be adjusted to decrease the risk of hypoglycemia during 
liraglutide treatment.  Basal rates will be decreased by 25% and meal boluses will be 
decreased by 33%. 
 
The first dose of liraglutide will be given at the study site.  Subjects will be given 0.6 mg 
subcutaneously.  Subjects will be taught how to use the delivery device at this visit. 
 
Subjects will be advised to take 0.6 mg of liraglutide subcutaneously every morning at 
about the same time. 
 
Subjects will be given a diary and be asked to record any episodes of hypoglycemia, as 
well as any other side effects such as nausea, decrease in appetite, and other problems. 
 
Subjects will be asked to keep a 4 day food record (three days, 1 weekend day).  
 
Subjects will be provided with contact information for the principal investigator in case 
of any problem or untoward side effect. They will be asked to notify the study staff for 
persistent low blood sugar (BS < 70 mg/dL), persistent high blood sugar (BS > 250 
mg/dL), or urine ketones.   
 
Subjects will be advised to return to clinic in 7 days. 
Visit 3 (Day 14):   This is the final study visit.  Subjects will come fasting for this visit.  The 
subject will not take liraglutide prior to coming to this visit but will bring the study drug to the 
visit. Subjects will bring the food records and diary of hypoglycemia to this visit. This visit will 
take approximately 4 hours.  At this visit, the following procedures will be performed: 
 
Records of blood sugars and CGM data will be obtained. 
 
Freestyle LibrePro device will be removed and data obtained. 
 
Blood sugars and insulin pump settings will be reviewed 
 
Record mean total daily insulin dose (previous 72 hours) from insulin pump. 
 
Liraglutide (0.6 mg subcutaneously) will be administered 45 minutes prior to the Mixed 
Meal Tolerance Test 
 
A Mixed Meal Tolerance test will be performed (see below). 
 
All study drug will be returned. 
 
Subjects will be advised to resume previous basal rates and carbohydrate ratios within 48 
hours of final study visit.   
Mixed Meal Tolerance Test (MMTT). This test will be done at Visit 2 and Visit 3.  The MMTT 
is a test to measure blood sugar levels in response to a meal and the amount of glucagon that is 
produced in response to changes in blood sugar.  Prior to the test, a catheter will be placed to reduce 
the number of needle sticks during the test. Subjects will drink 240 ml of a high protein nutrition 
drink (BOOST).  An appropriate amount of insulin for the carbohydrate intake of the meal 
challenge will be administered via insulin pump to taking the drink.  Blood will drawn once before 
the meal and 8 times during the meal over 3 hours.  The total amount of blood that will be drawn 
is ~ 20 teaspoons (100 mL).  
The following parameters will be drawn for measurement during the MMTT 
 
Blood Glucose 
 
Glucagon 
 
 
Serum inflammatory mediators  
Blood samples (5 ml each) will be collected into fluoride (grey top) for glucose 
measurement and serum separator tubes for serum samples.  Glucose levels will be transported to 
the Kaleida Health Department of Pathology and Laboratory Medicine for analysis.  Samples for 
glucagon and serum inflammatory markers will be kept at room temperature prior to 
centrifugation.  Centrifugation will occur within one to two hours after collection of the 
samples.  The blood samples will be centrifuged for ten minutes at room temperature at a 
relative centrifugal force of 1500xg.  Serum samples will be aliquoted and frozen at -


 
Page 14 of 32 
Revised: July 24, 2018 
20ºC.  All samples will be labeled with subject name, date of birth, subject number, date 
of collection, and time of collection.  Subject number will be assigned sequentially based 
on entry into the study.  All relevant data regarding the samples will be entered into a 
computer database .  Sample assays will be performed in duplicate to control for intra-
assay variability. 
8.3 Describe procedures performed to lessen the probability or 
magnitude of risks. 
Response: All study tasks will be performed in a quiet and private room.  Subjects 
will be advised of potential adverse events and provided with contact information 
for Dr. Mastrandrea.  Insulin doses will be lowered in order to decrease the risk of 
hypoglycemia during the liraglutide treatment week.    
8.4 Describe all drugs and devices used in the research and the purpose 
of their use, and their regulatory approval status. 
Response: Study drug = liraglutide, a GLP-1 analogue.  This drug is 
approved for management of Type 2 diabetes in adults.  The liraglutide 
pen device will be returned following completion of the study, and any 
remaining drug will be destroyed at the study site by the study 
investigators.  The principal investigators will be responsible for ensuring 
that the liraglutide devices will only be used by individuals who have 
provided consent and who have agreed to participate in the study.  See 
attached FDA IND exemption for this study. 
8.5 Describe the source records that will be used to collect data about 
subjects. (Attach all surveys, scripts, and data collection forms.) 
Response:  
A data collection tool (attached) will be used to collect the following data 
from the patient or from the medical record: 
 Age (Year-months; based on date of birth) 
 Sex 
 Date of diabetes diagnosis 
 Insurance Type 
 Height (cm) and weight (kg) 
 Body mass index (BMI) 
 Blood pressure 
 Hemoglobin A1c (POS) 
 Insulin regimen and daily insulin use 
 Other medications 
 Side effect diary 
 4 day food records 
In addition, the insulin pump download and blood glucose monitor 
downloads will be reviewed to collect the following information: 
For all subjects: 


 
Page 15 of 32 
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 Number of blood sugar checks/day (average of 7 days prior to visit) 
 Total basal dose 
 Total daily insulin dose 
 %basal/%bolus 
 Boluses recorded/day 
 Grams of carbohydrate recorded/day 
Data will be recorded on the source document that carries the subject identifier 
number. Data will then be transferred to an Excel spreadsheet – no identifying 
data will be recorded in this spreadsheet.  
8.6 What data will be collected including long-term follow-up. 
Response: See above. 
8.7 For HUD uses provide a description of the device, a summary of 
how you propose to use the device, including a description of any 
screening procedures, the HUD procedure, and any patient follow-
up visits, tests or procedures. 
Response: N/A 
9.0 
Data and Specimen Banking 
9.1 If data or specimens will be banked for future use, describe where 
the data/specimens will be stored, how long they will be stored, how 
the data/specimens will be accessed, and who will have access to the 
data/specimens. 
Response: Data will be stored on a password-protected computer in a 
locked office.  The principal investigator will have access to the data for 
data entry and analysis. Biological specimens collected during the MMTT 
will be stored in -80°C freezer at Jacobs School of Medicine, 5th floor.   
Only Dr. Mastrandrea or research assistants will have access to these 
specimens.  Data will be stored until study completion. Samples will be 
stored until study completion.   
9.2 List the data to be stored or associated with each specimen. 
Response: Data will be stored with subject identifier number.  Specimens 
will have recorded subject identifier, as well as time point during MMTT, 
and date of collection.  
9.3 Describe the procedures to release data or specimens, including: the 
process to request a release, approvals required for release, who 
can obtain data or specimens, and the data to be provided with 
specimens. 
Response: No data will be released. 
10.0 Data Management 


 
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10.1 Describe the data analysis plan, including any statistical 
procedures. 
Response: Response: For statistical purposes, the primary endpoint of the study 
is to detect a difference between untreated and treated periods in the change from 
baseline in mean weekly blood glucose concentrations The statistical analysis will be 
carried out using analysis of variance (ANOVA) and tested at the 0.05 level. The results 
will be computed as mean±SD. 
The secondary end points based on glycemic changes will include the difference 
from baseline in standard deviations of the mean weekly glucose concentrations, mean 
fasting blood glucose concentrations, the duration of time spent in hyperglycemia 
(>150mg/dl, > 200mg/dl, > 250mg/dl) and hypoglycemia (< 70mg/dl, < 40mg/dl), and 
insulin dosage. A reduction in the area under curve following the meal will constitute 
another secondary end point. Within subject comparisons of the magnitude of change 
from baseline will also be made for these glycemia related secondary endpoints using 
student’s t-test. Comparisons for these and the primary endpoints will also be made using 
the paired t-test or Wilcoxson’s test for paired data for each subject. Additional secondary 
end-points of the study will be change from baseline in 1) mean weekly blood glucose 2) 
glucagon area under the curve concentrations following meal challenge 3) change in daily 
insulin dose (total dose and units/kg) 4) caloric intake based on 4 day food records and 5) 
change in serum adiponectin and CRP levels before and after initiation of liraglutide 
treatment. The relation between change in postprandial sugars, glucagon, and total daily 
insulin dose will be studied by regression analysis to evaluate the relative contribution of 
each of these parameters to the improvement in post-prandial blood sugars 
10.2 Provide a power analysis. 
Response: A previous study (5) in adults with well-controlled diabetes demonstrated that 
liraglutide treatment decreased mean weekly blood sugars by 22 mg/dL.  Based on these 
results, a priori power analysis indicates that 9 subjects will need to be enrolled in the 
study to detect a change in mean weekly blood sugars of 22 ± 20 mg/dL between 
untreated and treated periods with 80% power and alpha error of 0.05 (paired t-test). We 
will enroll up to 12 subjects for this study. 
10.3 Describe the steps that will be taken secure the data (e.g., training, 
authorization of access, password protection, encryption, physical 
controls, certificates of confidentiality, and separation of identifiers 
and data) during storage, use, and transmission. 
Response: All primary data collection tools will be stored in Dr. 
Mastrandrea’s office. All personal information, signed consents/assents 
and patient blood sugar logs/food diaries will be stored in a locked filing 
cabinet in principal investigator’s locked office. Data will be entered into a 
password protected Excel Spreadsheet. Access to the computer system is 
also password protected and only members of the study team will have 
access to the electronic data.  All members of the team have completed 
CITI and GRP training. Data will not be transmitted.  
10.4 Describe any procedures that will be used for quality control of 
collected data. 


 
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Response: Dr. Mastrandrea will be responsible for review of data on a 
regular basis to ensure that collected data is being entered correctly.    
10.5 Describe how data and specimens will be handled study-wide: 
Response: Data will be entered electronically in a timely manner. 
Downloads of meters/pumps are scanned into the medical record as part of 
standard of care.   
10.6 What information will be included in that data or associated with the 
specimens? 
Response: See data collection tool. Each subject will be assigned a unique 
study identification number.  
10.7 Where and how data or specimens will be stored? 
Response: All personal information, signed consents/assents and patient 
blood sugar logs/food diaries will be stored in a locked filing cabinet in 
principal investigator’s locked office.  Data will be stored on a password-
protected computer in Dr. Mastrandrea’s office. 
10.8 How long the data or specimens will be stored? 
Response: Data will be stored for 5 years after the completion of the study. 
10.9 Who will have access to the data or specimens? 
 
Response: Study data will be stored on a password-protected computer that is 
 
limited to the principal investigator and co-investigators.    
 Who is responsible for receipt or transmission of the data or specimens? 
Response: Dr. Mastrandrea 
10.10How data and specimens will be transported? 
Response: Data will be stored on password-protected computer. Data will 
not be transported.  
11.0 Provisions to Monitor the Data and Ensure the Safety of Subjects 
11.1 Describe the plan to periodically evaluate the data collected 
regarding both harms and benefits to determine whether subjects 
remain safe.   
Response: Dr. Mastrandrea is responsible for review of data on a regular 
basis to ensure that collected data is being entered correctly. All 
unforeseen events during the study tasks will be reported immediately to 
the principal investigator; if necessary, they will be reported to the IRB. 
11.2 Describe what data are reviewed, including safety data, untoward 
events, and efficacy data. 
Response: Data related to study tasks will be reviewed.  
11.3 Describe how the safety information will be collected (e.g., with case 
report forms, at study visits, by telephone calls with participants). 


 
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Revised: July 24, 2018 
Response: Safety information will be documented on the data collection 
tool as necessary. 
11.4 Describe the frequency of data collection, including when safety 
data collection starts. 
Response: Dr. Mastrandrea is responsible for collection and review of all 
data.  
11.5 Describe who will review the data. 
Response: Dr. Mastrandrea 
11.6 Describe the frequency or periodicity of review of cumulative data. 
Response: see above 
11.7 Describe the statistical tests for analyzing the safety data to 
determine whether harm is occurring. 
Response: Number of severe hypoglycemic events will be documented.  
The rate of severe hypoglycemia will be compared to historical data.  
11.8 Describe any conditions that trigger an immediate suspension of the 
research. 
Response: Episode of pancreatitis.   
12.0 Withdrawal of Subjects 
12.1 Describe anticipated circumstances under which subjects will be 
withdrawn from the research without their consent. 
Response: A subject may be withdrawn from the study if they are having 
significant side effects to liraglutide – nausea/vomiting, severe 
hypoglycemia.  In addition, a subject may be withdrawn if they are having 
difficulty completing the study tasks essential for data collection.  
12.2 Describe any procedures for orderly termination. 
Response: Subject data will not be included in the analysis, and the subject 
will be replaced.  All subjects will receive study compensation even if 
they are not included in the finals study analysis. 
12.3 Describe procedures that will be followed when subjects withdraw 
from the research, including partial withdrawal from procedures 
with continued data collection. 
Response: If a subject is withdrawn from the research prior to de-
identification of data, no data will be used for the subject. The data will be 
expunged and the subject will be replaced. If a subject withdraws from the 
study after de-identification of data, no further data will be collected for 
that subject.  However, any data already collected may be included in the 
final analysis.   
13.0 Risks to Subjects 


 
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Revised: July 24, 2018 
13.1 List the reasonably foreseeable risks, discomforts, hazards, or 
inconveniences to the subjects related the subjects’ participation in 
the research. Include as may be useful for the IRB’s consideration, a 
description of the probability, magnitude, duration, and reversibility 
of the risks. Consider physical, psychological, social, legal, and 
economic risks. 
Response: Types of Risk:   
Important Safety Information (see attached product information):  In animal studies, 
liraglutide caused rats and mice to develop thyroid tumors, some of which were cancers. 
It is not known whether liraglutide causes thyroid tumors or a type of thyroid cancer 
called medullary thyroid cancer in humans.  Subjects with a history or family history of 
medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) will 
not be enrolled in this study.   
 
Treatment with GLP-1 is associated with inflammation of the pancreas 
(pancreatitis) which may be severe and can lead to death. Certain conditions increase the 
risk of developing pancreatitis including history of pancreatitis, gallstones, alcoholism, or 
high triglyceride levels.  We will review the subject’s medical record to assess for any of 
these risk factors.  In addition, subjects will be excluded if they have a history of 
pancreatitis.  While taking liraglutide, the subjects will be counseled to notify study staff 
if they develop severe abdominal pain.  Should this occur, they will be advised to 
discontinue liraglutide and testing for pancreatitis will be performed (serum amylase and 
lipase).  Subjects will also be counseled not to consume alcohol while enrolled in this 
study. 
 
Glucagon-like peptide 1 is an incretin hormone that is released in response to 
ingestion of food.  Long-acting GLP-1 analogues and drugs which inhibit the metabolism 
of GLP-1 are FDA-approved as adjuvant therapy for the treatment of Type 2 diabetes.  
These drugs are currently not approved for use in the T1DM population.  Individuals 
treated with GLP-1 analogues are at increased risk for hypoglycemia.  It is recommended 
that patients treated with insulin secretagogue therapies (ie sulfonylureas), have their 
secretagogue dose decrease when GLP-1 analogue therapy is initiated.  In this study, 
subjects have T1DM and are reliant on insulin for blood sugar control.  In order to 
decrease the risk of hypoglycemia in this population, subjects will be counseled to 
decrease their basal insulin rates by 25% and their bolus insulin coverage for 
carbohydrates by 30% during the seven days when they are receiving liraglutide. All 
study subjects will be advised to check their blood sugar if they experience any 
symptoms consistent with hypoglycemia.  They will be asked to contact the study team 
for persistent hypoglycemia while taking liraglutide. In addition, because insulin doses 
will be decrease significantly when liraglutide is initiated, there is the risk that subjects 
will experience hyperglycemia and may develop ketonuria.  Subjects will be advised to 
contact the study team for persistent hyperglycemia and/or presence of urine ketones.  
The insulin dose will be increased to address this concern.  
 
The most common side effects experiences by adults taking liraglutide include 
headache, nausea, and diarrhea.  Nausea is most common when first starting liraglutide 
but generally decreases with time.  Subjects may also feel less hungry while taking 
liraglutide.  We will monitor for these and additional side effects during the study. 


 
Page 20 of 32 
Revised: July 24, 2018 
Physical Risks:  In addition to the physical risks described above related to liraglutide, 
adverse events that are outlined in the informed consent include pain, bruising, or 
infection at the blood draw site.  In addition, a subject may experience light-headedness 
or may faint during the MMTT.  These events will be recorded and maintained as part of 
the study record.  To decrease the likelihood of these risks, staff trained in performance in 
MMTT will perform the test and the subjects will be observed after the test.  Subjects 
may develop a skin infection at the site of insertion of CGM.   We will alert subjects to 
monitor for any redness or swelling at the site and advise them to call Dr. Mastrandrea.  
The principal investigators are responsible for ensuring that all adverse risks are 
recorded.   The study will be performed in accordance with the ethical principles as 
outlined in the Declaration of Helsinki and are consistent with Good Clinical Practice.  
Privacy Risks: There is a risk to privacy. The study tasks will be performed in a quiet, 
private office. 
Risk of Loss of Confidentiality:  There is a small risk of loss of confidentiality.  The 
informed consent contains wording that complies with relevant data protection and 
privacy legislation. By signing the consent/assent, the subjects/parents/guardians 
authorize the collection, use, and disclosure of their study data by the principal 
investigators and by those who need the information for the study.  The informed consent 
also explains that the study data will be stored in a computer database, with 
confidentiality maintained in accordance with national data legislation.  The informed 
consent also explains that in order to verify data, it may be necessary to access the 
subject’s medical record at a later time in the study.  The computer database, informed 
consents, and all data will be secured within Dr. Mastrandrea’s locked office within the 
Division of Pediatric Endocrinology. 
Psychological Risks:  Subjects may experience negative emotions if we are able to 
demonstrate that liraglutide has a positive effect on glycemia. Subjects will be aware of 
their blood sugars throughout the study and may feel a sense of loss when the drug is 
discontinued at the end of the study.  At the onset of the study, we will counsel these 
subjects that this study is being performed to test the hypothesis that liraglutide improves 
mean weekly blood glucose levels.  They will be made aware that the drug is not 
approved by the FDA for treatment/management of T1DM. 
13.2 If applicable, indicate which procedures may have risks to the 
subjects that are currently unforeseeable. 
Response: Subjects may experience a side effect to liraglutide that is previously 
undescribed.  
13.3 If applicable, indicate which procedures may have risks to an 
embryo or fetus should the subject be or become pregnant. 
Response: N/A 
13.4 If applicable, describe risks to others who are not subjects. 
Response: N/A 
14.0 Potential Benefits to Subjects 


 
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14.1 Describe the potential benefits that individual subjects may 
experience from taking part in the research. Include as may be 
useful for the IRB’s consideration, the probability, magnitude, and 
duration of the potential benefits. 
Response: Potential Benefits:   Subjects may benefit directly from this study by 
receiving intensified diabetes care and review of their blood sugars with subsequent 
adjustment of insulin doses.  The subjects may also experience improvements in their 
blood sugars, albeit temporary, during the treatment phase of the study.   The results of 
the study may be used to develop longer term, randomized, double-blind, placebo-
controlled studies to test the efficacy of liraglutide in management of T1DM. 
14.2 Indicate if there is no direct benefit. Do not include benefits to 
society or others. 
Response: See above 
15.0 Vulnerable Populations 
15.1 If the research involves individuals who are vulnerable to coercion 
or undue influence, describe additional safeguards included to 
protect their rights and welfare. 
 
If the research involves pregnant women, review 
“CHECKLIST: Pregnant Women (HRP-412)” to ensure that 
you have provided sufficient information. 
 
If the research involves neonates of uncertain viability or non-
viable neonates, review “CHECKLIST: Neonates (HRP-413)” 
or “HRP-414 – CHECKLIST: Neonates of Uncertain Viability 
(HRP-414)” to ensure that you have provided sufficient 
information. 
 
If the research involves prisoners, review “CHECKLIST: 
Prisoners (HRP-415)” to ensure that you have provided 
sufficient information. 
 
If the research involves persons who have not attained the 
legal age for consent to treatments or procedures involved in 
the research (“children”), review the “CHECKLIST: Children 
(HRP-416)” to ensure that you have provided sufficient 
information. 
 
If the research involves cognitively impaired adults, review 
“CHECKLIST: Cognitively Impaired Adults (HRP-417)” to 
ensure that you have provided sufficient information. 
 
Consider if other specifically targeted populations such as 
students, employees of a specific firm or 
educationally/economically disadvantaged persons are 
vulnerable to coercion or undue influence.  The checklists 
listed above for other populations should be used as a guide to 
ensure that you have provided sufficient information.  


 
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Revised: July 24, 2018 
Response: HRP-416 has been reviewed.  Children will have the 
opportunity to provide assent.  
16.0 Community-Based Participatory Research 
16.1 Describe involvement of the community in the design and conduct of 
the research. 
Response: N/A 
Note: “Community-based Participatory Research” is a collaborative 
approach to research that equitably involves all partners in the 
research process and recognizes the unique strengths that each 
brings. Community-based Participatory Research begins with a 
research topic of importance to the community, has the aim of 
combining knowledge with action and achieving social change to 
improve health outcomes and eliminate health disparities. 
17.0 Sharing of Results with Subjects 
17.1 Describe whether or not results (study results or individual subject 
results, such as results of investigational diagnostic tests, genetic 
tests, or incidental findings) will be shared with subjects or others 
(e.g., the subject’s primary care physicians) and if so, describe how 
it will be shared. 
Response: No results will be shared. 
18.0 Setting 
18.1 Describe the sites or locations where your research team will 
conduct the research.  
Response: The research will be conducted at the UBMD Pediatrics, 
Division of Endocrinology/Diabetes clinic space at 1001 Main Street, 
Buffalo, NY. All study testing will be done in a designated private and 
quiet area. For some subjects, Visits 2 and 3 will take place at the 
University Commons, University Pediatrics Associates Suite 5, Amherst, 
New York. 
18.2 Identify where your research team will identify and recruit potential 
subjects. 
Response: The research team will identify potential subjects at their clinic visit at the 
Diabetes Center . During visit 1, eligibility for the study will be determined.  The study 
protocol will be reviewed with the subject and parent/guardian.  Informed consent will be 
signed by the parent/guardian or subject (age≥ 18 years) with assent provided by subjects 
under 18 years of age.   Subjects will be provided copies of the consent/study protocol 
and will be advised to notify study staff if they choose not to participate in the study.  
Signed consents will be stored in a locked file cabinet in the PI’s locked office.  Subjects 
will be provided with copies of signed consents. 
18.3 Identify where research procedures will be performed. 


 
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Revised: July 24, 2018 
Response: All research procedures will be performed in a designated 
private and quiet research area in the UBMD Pediatrics, Division of 
Endocrinology/Diabetes clinic space at 1001 Main Street, Buffalo, NY.  
For some subjects, Visits 2 and 3 will take place at the University 
Commons, University Pediatrics Associates Suite 5, Amherst, New York. 
18.4 Describe the composition and involvement of any community 
advisory board. 
Response: N/A 
18.5 For research conducted outside of the organization and its affiliates 
describe: 
 Site-specific regulations or customs affecting the research for 
research outside the organization. 
 Local scientific and ethical review structure outside the 
organization. 
Response: N/A 
19.0 Resources Available 
19.1 Describe the qualifications (e.g., training, experience, oversight) of 
you and your staff as required to perform their role. When 
applicable describe their knowledge of the local study sites, culture, 
and society. Provide enough information to convince the IRB that 
you have qualified staff for the proposed research. Note- If you 
specify a person by name, a change to that person will require prior 
approval by the IRB. If you specify people by role (e.g., coordinator, 
research assistant, co-investigator, or pharmacist), a change to that 
person will not usually require prior approval by the IRB, provided 
that person meets the qualifications described to fulfill their roles. 
Response: Response: The principal investigator is a board-certified 
pediatric endocrinologist with proper IRB training as well as HIPAA 
training. The research staff work in the diabetes clinics and have 
experience with type 1 diabetes. The research staff has IRB training as 
well as HIPAA training. Study staff has experience administering the 
study tasks to be completed by subjects. All staff has completed CITI and 
GRP training.  The study staff has experience in performing MMTTs. 
Describe other resources available to conduct the research: For example, 
as appropriate:  N/A 
19.2 Justify the feasibility of recruiting the required number of suitable 
subjects within the agreed recruitment period. For example, how 
many potential subjects do you have access to? What percentage of 
those potential subjects do you need to recruit? 


 
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Revised: July 24, 2018 
Response: The Diabetes Center outpatient clinic provides care for 325 patients in the 
proposed age range for the study.   Of those, ~130 are managed with insulin pump 
therapy.  This is the relevant population for recruitment.    
19.3 Describe the time that you will devote to conducting and completing 
the research. 
Response: We have dedicated research staff.  Dr. Mastrandrea will provide 
5% of her professional time towards management of this project.  There 
are three study visits for each subject. 
19.4 Describe your facilities. 
Response: For obtaining consent, the UBMD Pediatrics Outpatient clinic 
will be utilized. It has 8 patient exam rooms, 1 vital room and 1 lab room. 
Our diabetes department has a private research rooms that will be used for 
study tasks.  For some subjects, Visits 2 and 3 will take place at the 
University Commons, University Pediatrics Associates Suite 5, Amherst, 
New York.  
19.5 Describe the availability of medical or psychological resources that 
subjects might need as a result of an anticipated consequences of the 
human research. 
Response: Dr. Mastrandrea will be available to discuss any 
questions/concerns related to the study. 
19.6 Describe your process to ensure that all persons assisting with the 
research are adequately informed about the protocol, the research 
procedures, and their duties and functions. 
Response: All personnel involved in the research will review the protocol, 
consent, and also attend any training to review study procedures 
20.0 Prior Approvals 
20.1 Describe any approvals that will be obtained prior to commencing 
the research. (E.g., school, external site. funding agency, laboratory, 
radiation safety, or biosafety approval.) 
Response: N/A 
21.0 Recruitment Methods 
21.1 Describe when, where, and how potential subjects will be recruited. 
Response: The subjects will be recruited from UBMD Pediatrics, Division of 
Endocrinology/Diabetes clinic space at 1001 Main Street, Buffalo, NY during 
their outpatient clinic visits.  Clinic rosters will be reviewed prior to clinic to 
identify potential subjects.  
21.2 Describe the source of subjects. 
Response: All potential subjects receive their diabetes care at the UBMD 
Pediatrics Division of Endocrinology/Diabetes.   


 
Page 25 of 32 
Revised: July 24, 2018 
21.3 Describe the methods that will be used to identify potential subjects. 
Response: Potential subjects will be identified either from a) outpatient 
clinic schedules 2) diabetes clinic.  We will identify individuals with Type 
1 diabetes for > 1 year who are managed with insulin pump and approach 
them regarding the study.  
21.4 Describe materials that will be used to recruit subjects. (Attach 
copies of these documents with the application. For advertisements, 
attach the final copy of printed advertisements. When advertisements 
are taped for broadcast, attach the final audio/video tape. You may 
submit the wording of the advertisement prior to taping to preclude 
re-taping because of inappropriate wording, provided the IRB 
reviews the final audio/video tape.) 
Response: N/A 
21.5 Describe the amount and timing of any payments to subjects. 
Response: Subjects will receive a $25 gift card/study visit when they have 
completed the study procedures. The gift card will be received at the end 
of each study visit. In the case where a subject receives a gift card of $50 
or greater, we will alert them that they will need to complete an IRS Form 
W-9.  
22.0 Local Number of Subjects 
22.1 Indicate the total number of subjects to be accrued locally. 
Response: 12 
22.2 If applicable, distinguish between the number of subjects who are 
expected to be enrolled and screened, and the number of subjects 
needed to complete the research procedures (i.e., numbers of 
subjects excluding screen failures.) 
Response: We expect that all subjects who meet inclusion/exclusion 
criteria and sign informed consent/assent will complete the study.  
23.0 Confidentiality 
Describe the local procedures for maintenance of confidentiality. 
23.1 Where and how data or specimens will be stored locally? 
Response: Each subject will be assigned a unique study identification 
number.  All study data will be de-identified. Downloads of meters/pumps 
will be stored in Dr. Mastrandrea’s office. Data will be extracted from 
those records.  Study data will be stored on a password-protected 
computer that is limited to the principal investigator. 
If a subject receives a gift card of value $50 or greater, we will ask them to 
complete an IRS Form W-9. This form will be held confidentially in Dr. 
Mastrandrea’s office and those responsible for administering the research 
funds.  


 
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Revised: July 24, 2018 
23.2 How long the data or specimens will be stored locally? 
Response: Data will be stored for 5 years after the completion of the study. 
23.3 Who will have access to the data or specimens locally? 
Response: Only study personnel. 
23.4 Who is responsible for receipt or transmission of the data or 
specimens locally? 
Response: N/A 
23.5 How data and specimens will be transported locally? 
Response: N/A 
24.0 Provisions to Protect the Privacy Interests of Subjects 
24.1 Describe the steps that will be taken to protect subjects’ privacy 
interests. “Privacy interest” refers to a person’s desire to place 
limits on whom they interact or whom they provide personal 
information. 
Response: The study will be introduced to potential subjects in 
examination rooms with doors closed.  Subjects who consent/assent to the 
study will provide authorization to access private health information that is 
to be collected for the study.  All study testing will be done in a designated 
private and quiet area.  Individuals not involved in the study will not 
observe the subject performing the indicated tasks. 
24.2 Describe what steps you will take to make the subjects feel at ease 
with the research situation in terms of the questions being asked and 
the procedures being performed. “At ease” does not refer to 
physical discomfort, but the sense of intrusiveness a subject might 
experience in response to questions, examinations, and procedures. 
Response: Potential subjects will be able to review the consent thoroughly 
and will be able to ask questions about the study prior to providing 
consent.  The study tasks will be done in a designated private and quiet 
area.   
24.3 Indicate how the research team is permitted to access any sources of 
information about the subjects. 
Response: The study team has access to the electronic medical record 
(AllScripts EHR) in order to collect relevant data related to the study.  All 
subjects will sign HIPAA authorization; except for the data collected from 
the study tasks, all other information is collected as part of standard of 
care during a diabetes clinic visit. 
25.0 Compensation for Research-Related Injury 
25.1 If the research involves more than Minimal Risk to subjects, describe 
the available compensation in the event of research related injury. 


 
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Response:  
If you need medical care because of taking part in this research study, 
contact the investigator and medical care will be made available. 
Generally, this care will be billed to you, your insurance or other third 
party. The University at Buffalo and Kaleida Health has no program to 
pay for medical care for research-related injury.  
 
25.2 Provide a copy of contract language, if any, relevant to 
compensation for research-related injury. 
Response: N/A 
26.0 Economic Burden to Subjects 
26.1 Describe any costs that subjects may be responsible for because of 
participation in the research. 
Response: There are no costs associated with this research. 
27.0 Consent Process 
27.1 Indicate whether you will be obtaining consent 
Response: Parental permission and/or consent will be obtained for all 
subjects.  
27.2 Describe where  the consent process take place 
Response: The consent process will take place in the exam room in the 
outpatient UBMD Pediatrics Diabetes clinics at 1001 Main Street, 4th 
Floor Buffalo, NY.   
27.3 Describe any waiting period available between informing the 
prospective subject and obtaining the consent. 
Response: Some prospective subjects may decide to review the consent at 
home before deciding to participate.  The period of time between 
introducing the study and obtaining consent could be as long as 3 months. 
Consent will only be obtained from individuals who are in agreement to 
the study.   
27.4 Describe any process to ensure ongoing consent. 
Response: Subjects will be asked at the beginning of Visit 2 and Visit 3 
whether they are willing to continue with the study.  In the unlikely event 
that an individual turns 18 years between the time of signing assent and 
performing study tasks, that individual will be reconsented and asked to 
sign the adult consent form.  
27.5 Describe whether you will be following “SOP: Informed Consent 
Process for Research (HRP-090).” If not, describe: 


 
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 
The role of the individuals listed in the application as being 
involved in the consent process. 
 
The time that will be devoted to the consent discussion. 
 
Steps that will be taken to minimize the possibility of coercion 
or undue influence. 
 
Steps that will be taken to ensure the subjects’ understanding. 
Response: SOP: Informed Consent Process for Research (HRP-090) will 
be used.  
Non-English Speaking Subjects  
27.6 Indicate what language(s) other than English are likely to be 
spoken/understood by your prospective study population or their 
legally authorized representatives. 
Response: The most common language other than English is Spanish. 
27.7 If subjects who do not speak English will be enrolled, describe the 
process to ensure that the oral and written information provided to 
those subjects will be in that language. Indicate the language that 
will be used by those obtaining consent. 
Response: Subjects who do not speak English will not be enrolled.  
Waiver or Alteration of Consent Process (consent will not be obtained, 
required information will not be disclosed, or the research involves 
deception) 
27.8 Review the “CHECKLIST: Waiver or Alteration of Consent Process 
(HRP-410)” to ensure you have provided sufficient information for 
the IRB to make these determinations. Provide any additional 
information necessary here: 
Response: N/A 
27.9 If the research involves a waiver the consent process for planned 
emergency research, please review the “CHECKLIST: Waiver of 
Consent for Emergency Research (HRP-419)” to ensure you have 
provided sufficient information for the IRB to make these 
determinations. Provide any additional information necessary here: 
Response: N/A 
Subjects who are not yet adults (infants, children, teenagers) 
27.10Describe the criteria that will be used to determine whether a 
prospective subject has not attained the legal age for consent to 
treatments or procedures involved in the research under the 
applicable law of the jurisdiction in which the research will be 
conducted. (E.g., individuals under the age of 18 years.) For 
research conducted in NY state, review “SOP: Legally Authorized 


 
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Revised: July 24, 2018 
Representatives, Children, and Guardians (HRP-013)” to be aware 
of which individuals in the state meet the definition of “children.” 
Response: We will use the date of birth to determine whether the 
individual has obtained legal age for consent.  Any individual ≥18 years 
may provide consent.  Assent will be obtained for all other subjects in 
addition to parental permission.   
27.11For research conducted outside of NY state, provide information that 
describes which persons have not attained the legal age for consent 
to treatments or procedures involved the research, under the 
applicable law of the jurisdiction in which research will be 
conducted. One method of obtaining this information is to have a 
legal counsel or authority review your protocol along the definition 
of “children” in “SOP: Legally Authorized Representatives, 
Children, and Guardians (HRP-013).” 
Response: N/A 
27.12Describe whether parental permission will be obtained from: 
 
Both parents unless 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. 
 
One parent even if the other parent is alive, known, competent, 
reasonably available, and shares legal responsibility for the 
care and custody of the child. 
Response: Permission will be obtained from one parent.  
27.13Describe whether permission will be obtained from individuals other 
than parents, and if so, who will be allowed to provide permission. 
Describe the process used to determine these individuals’ authority 
to consent to each child’s general medical care. 
Response: Permission may be obtained by custodial guardians.  We will 
require legal documentation prior to obtaining consent to permission for 
these individuals. 
27.14Indicate whether assent will be obtained from all, some, or none of 
the children. If assent will be obtained from some children, indicate 
which children will be required to assent. 
Response: All children age <18 years will provide assent. 
27.15When assent of children is obtained describe whether and how it will 
be documented. 
Response: Assent will be documented on a separate assent form which 
will be signed by the child.  A copy of all documents will be provided to 
the family.  


 
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Revised: July 24, 2018 
Cognitively Impaired Adults 
27.16Describe the process to determine whether an individual is capable 
of consent. The IRB sometimes allows the person obtaining assent to 
document assent on the consent document and does not 
automatically require assent documents to be used. 
Response: N/A 
Adults Unable to Consent 
When a person is not capable of consent due to cognitive impairment, a 
legally authorized representative should be used to provide consent and, 
where possible, assent of the individual should also be solicited. 
27.17List the individuals from whom permission will be obtained in order 
of priority. (e.g., durable power of attorney for health care, court 
appointed guardian for health care decisions, spouse, and adult 
child.)  For research conducted in NY state, review “SOP: Legally 
Authorized Representatives, Children, and Guardians (HRP-013)” 
to be aware of which individuals in the state meet the definition of 
“legally authorized representative.”  The list in the consent template 
signature section corresponds to the priority list for NYS.   
Response: N/A 
27.18For research conducted outside of NY state, provide information that 
describes which individuals are authorized under applicable law to 
consent on behalf of a prospective subject to their participation in 
the procedure(s) involved in this research. One method of obtaining 
this information is to have a legal counsel or authority review your 
protocol along the definition of “legally authorized representative” 
in “SOP: Legally Authorized Representatives, Children, and 
Guardians (HRP-013).” 
Response: N/A 
27.19Describe the process for assent of the subjects. Indicate whether: 
 
Assent will be required of all, some, or none of the subjects. If 
some, indicated, which subjects will be required to assent and 
which will not. 
 
If assent will not be obtained from some or all subjects, an 
explanation of why not. 
 
Describe whether assent of the subjects will be documented 
and the process to document assent. The IRB allows the person 
obtaining assent to document assent on the consent document 
and does not routinely require assent documents and does not 
routinely require subjects to sign assent documents. 
Response: Assent will be obtained from all subjects age 15 - <18 years. A 
separate assent form will be provided. 


 
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27.20For HUD uses provide a description of how the patient will be 
informed of the potential risks and benefits of the HUD and any 
procedures associated with its use. 
Response: N/A 
28.0 Process to Document Consent in Writing 
 
If your research presents no more than minimal risk of harm to subjects and 
involves no procedures for which written documentation of consent is normally 
required outside of the research context, the IRB will generally waive the 
requirement to obtain written documentation of consent. 
(If you will document consent in writing, attach a consent document. If you will 
obtain consent, but not document consent in writing, attach a consent script. 
Review “CHECKLIST: Waiver of Written Documentation of Consent (HRP-411)” 
to ensure that you have provided sufficient information. You may use 
“TEMPLATE CONSENT DOCUMENT (HRP-502)”to create the consent 
document or script.) 
28.1 Describe whether you will be following “SOP: Written 
Documentation of Consent (HRP-091).” If not, describe whether and 
how consent of the subject will be obtained including whether or not 
it will be documented in writing. 
Response: We will be following HRP-091. 
29.0 Drugs or Devices 
29.1 If the research involves drugs or device, describe your plans to store, 
handle, and administer those drugs or devices so that they will be 
used only on subjects and be used only by authorized investigators. 
Response: The study drug will be obtained from the CTRC pharmacy 
prior to visit 2. The study drug will be given directly to the subject at the 
end of Visit 2.  Subject will be advised that no other individuals may use 
the study drug.  They will also be advised to bring the study drug with 
them for Visit 3.  Study drug will be returned at the end of Visit 3 and will 
be disposed of by the principal investigator.  
If the drug is investigational (has an IND) or the device has an IDE or a 
claim of abbreviated IDE (non-significant risk device), include the 
following information: 
29.2 Identify the holder of the IND/IDE/Abbreviated IDE. 
Response: IND exempt per FDA. See attached letter. 
29.3 Explain procedures followed to comply with FDA sponsor 
requirements for the following: 


 
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Revised: July 24, 2018 
 
Applicable to: 
FDA Regulation 
IND Studies 
IDE studies 
Abbreviated 
IDE studies 
21 CFR 11 
X 
X 
 
21 CFR 54 
X 
X 
 
21 CFR 210 
X 
 
 
21 CFR 211 
X 
 
 
21 CFR 312 
X 
 
 
21 CFR 812 
 
X 
X 
21 CFR 820 
 
X 
 
Response: N/A