Investigation Into the Effects of Blood Glucose Levels Upon Eating Behavior in Lean and Obese Non-diabetic and Diabetic Subjects
Phase: NA
Conditions: Diabetes
Sponsor: Yale University

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YALE UNIVERSITY
                                  HUMAN INVESTIGATION COMMITTEE
                                     Application to Involve Human Subjects in Biomedical Research
100 FR1 (2013-1) 
DATE STAMPED-RECEIVED
PROTOCOL NUMBER
SECTION I: ADMINISTRATIVE INFORMATION
Title of Research Project: Investigation into the Effects of blood glucose levels upon eating behavior in lean 
and obese non-diabetic and diabetic subjects.
-
Principal Investigator: Renata Belfort De Aguiar
Yale Academic Appointment: Assistant  Professor
Department: Internal Medicine
Campus Address: Section of Endocrinology, TAC S-135
Campus Phone: 785-2440
Fax: 737-5558
Pager: 
E-mail: Renata.Aguiar@yale.edu
Protocol Correspondent Name & Address (if different than PI):
 
Campus Phone: 
Fax: 
E-mail: 
Yale Cancer Center CTO Protocol Correspondent Name & Address (if applicable):
Campus Phone: 
Fax: 
E-mail: 
Business Manager:
Campus Phone :
Fax :
E-mail
Faculty Advisor:(required if PI is a student, 
resident, fellow or other trainee)           
 NA
Yale Academic Appointment:
Campus Address: 
Campus Phone: 
Fax: 
Pager: 
E-mail: 
Please refer to the HIC website for application 
instructions and information required to complete 
this application.  The Instructions are available at 
http://www.yale.edu/hrpp/forms-
templates/biomedical.html 
Submit the original application and one (1) copy 
of all materials including relevant sections of the 
grant which funds this project (if applicable) to 
the HIC.  
HIC OFFICE USE ONLY
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Investigator Interests:
Does the principal investigator, or do any research personnel who are responsible for the design, 
conduct or reporting of this project or any of their family members (spouse or dependent child) 
have an incentive or interest, financial or otherwise, that may affect the protection of the human 
subjects involved in this project, the scientific objectivity of the research or its integrity? Note: 
The Principal Investigator (Project Director), upon consideration of the individual’s role and 
degree of independence in carrying out the work, will determine who is responsible for the 
design, conduct, or reporting of the research. 
See Disclosures and Management of Personal Interests in Human Research 
http://www.yale.edu/hrpp/policies/index.html#COI 
  Yes
  No
Do you or does anyone on the research team who is determined by you to be responsible for the 
design, conduct or reporting of this research have any patent (sole right to make, use or sell an 
invention) or copyright (exclusive rights to an original work) interests related to this research 
protocol?
  Yes
  No
If yes to either question above, list names of the investigator or responsible person:
The Yale University Principal Investigator, all Yale University co-investigators, and all Yale 
University individuals who are responsible for the design, conduct or reporting of research must 
have a current financial disclosure form on file with the University’s Conflict of Interest Office. 
Yale New Haven Hospital personnel who are listed as con-investigators on a protocol with a 
Yale University Principal Investigator must also have a current financial disclosure form on file 
with the University’s Conflict of Interest Office. If this has not been done, the individual(s) 
should follow this link to the COI Office Website to complete the form:  
http://www.yale.edu/coi/  
NOTE: The requirement for maintaining a current disclosure form on file with the University’s 
Conflict of Interest Office extends primarily to Yale University and Yale-New Haven Hospital 
personnel.  Whether or not they are required to maintain a disclosure form with the 
University’s Conflict of Interest Office, all investigators and individuals deemed otherwise 
responsible by the PI who are listed on the protocol are required to disclose to the PI any 
interests that are specific to this protocol.
SECTION II: GENERAL INFORMATION
1. Performing Organizations:  Identify the hospital, in-patient or outpatient facility, school or 
other agency that will serve as the location of the research.  Choose all that apply:
 
a. Internal Location[s of the Study:
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 Magnetic Resonance Research Center 
 Yale University PET Center
     (MR-TAC)   
 YCCI/Church Street Research Unit (CSRU)
 Yale Cancer Center/Clinical Trials Office (CTO)    
 YCCI/Hospital Research Unit (HRU)
 Yale Cancer Center/Smilow
 YCCI/Keck Laboratories
 Yale-New Haven Hospital
 Yale-New Haven Hospital—Saint Raphael Campus
 Cancer Data Repository/Tumor Registry
 Specify Other Yale Location:
b. External Location[s]:
 APT Foundation, Inc.
 Haskins Laboratories
 Connecticut Mental Health Center
 John B. Pierce Laboratory, Inc.
 Clinical Neuroscience Research Unit (CNRU) 
Veterans Affairs Hospital, West Haven
 Other Locations, Specify: 
 International Research Site 
(Specify location(s)):
c. Additional Required Documents (check all that apply):
 N/A
*YCCI-Scientific and Safety Committee (YCCI-SSC)
Approval Date: 
*Pediatric Protocol Review Committee (PPRC)
Approval Date: 
*YCC Protocol Review Committee (YRC-PRC)
Approval Date:
*Dept. of Veterans Affairs, West Haven VA HSS
Approval Date: 
*Radioactive Drug Research Committee (RDRC)
Approval Date: 
 YNHH-Radiation Safety Committee (YNHH-RSC)
Approval Date: 
 Magnetic Resonance Research Center PRC (MRRC-PRC)
Approval Date: 
 YSM/YNHH Cancer Data Repository (CaDR)
Approval Date: 
 Dept. of Lab Medicine request for services or specimens form
 Imaging on YNHH Diagnostic Radiology equipment request form (YDRCTO request) found at 
 http://radiology.yale.edu/research/ClinTrials.aspx)
*Approval from these committees is required before final HIC approval is granted. See instructions 
for documents required for initial submission and approval of the protocol. Allow sufficient time for 
these requests. Check with the oversight body for their time requirements.
2. Probable Duration of Project: State the expected duration of the project, including all 
follow-up and data analysis activities. December 2019
3. Research Type/Phase: (Check all that apply)
a. Study Type
   
 Single Center Study
   
 Multi-Center Study
Does the Yale PI serve as the PI of the multi-site study? Yes 
No 
  
 Coordinating Center/Data Management
  
 Other: 
b. Study Phase
 N/A
    
 Pilot
 Phase I
 Phase II
 Phase III
 Phase IV
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 Other (Specify) 
4. Area of Research: (Check all that apply) Note that these are overlapping definitions and 
more than one category may apply to your research protocol. Definitions for the following 
can be found  in the instructions section 4c:
 Clinical Research: Patient-Oriented
  
 Clinical Research: Outcomes and 
 Clinical Research: Epidemiologic and Behavioral 
                Health Services
 Translational Research #1 (“Bench-to-Bedside”)    
 Interdisciplinary Research
 Translational Research #2 (“Bedside-to-Community”) 
 Community-Based Research
5.   Is this study a clinical trial? Yes 
No 
NOTE the current ICMJE (International Committee of Medical Journal Editors) definition of a 
clinical trial: “any research study that prospectively assigns human participants or groups of humans 
to one or more health-related interventions to evaluate the effects on health outcomes.” Health-related 
interventions include any intervention used to modify a biomedical or health-related outcome (for 
example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and 
process-of-care changes). Health outcomes include any biomedical or health-related measures 
obtained in patients or participants, including pharmacokinetic measures and adverse events”
If yes, where is it registered?
Clinical Trials.gov registry 
Other (Specify) 
Registration of clinical trials at their initiation is required by the FDA, NIH and by the ICMJE.
If this study is registered on clinicaltrials.gov, there is new language in the consent form and compound 
authorization that should be used.
For more information on registering clinical trials, including whether your trial must be 
registered, see the YCCI webpage, http://ycci.yale.edu/researchers/ors/registerstudy.aspx or 
 contact YCCI at 203.785.3482)
6. Does the Clinical Trials Agreement (CTA) require compliance with ICH GCP (E6)? 
Yes 
 No
7. Will this study have a billable service? A Billable Service is defined as a service or procedure 
that will be ordered, performed or result in charging in EPIC for individuals who are enrolled in 
a clinical research study, regardless if the charge is intended to be paid by the subject/their 
insurance or the research study.
Yes 
 No
If you answered "yes", this study will need to be set up in OnCore Support
http://medicine.yale.edu/ymg/systems/ppm/index.aspx 
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8.. Are there any procedures involved in this protocol that will be performed at YNHH or one of 
its affiliated entities?  Yes ___ No __X_  If Yes, please answer questions a through c and note 
instructions below.  If No, proceed to Section III.
a. Does your YNHH privilege delineation currently include the specific procedure that you will 
perform?
b. Will you be using any new equipment or equipment that you have not used in the past for 
this procedure?
 
c. Will a novel approach using existing equipment be applied?
 
If you answered “no” to question 7a, or "yes" to question 7b or c, please contact the YNHH 
Department of Physician Services (688-2615) for prior approval before commencing with your 
research protocol.
SECTION IV:
 PRINCIPAL INVESTIGATOR/FACULTY ADVISOR/ DEPARTMENT CHAIR 
AGREEMENT
As the principal investigator of this research project, I certify that:

The information provided in this application is complete and accurate.

I assume full responsibility for the protection of human subjects and the proper conduct of the
      research.

Subject safety will be of paramount concern, and every effort will be made to protect subjects’
      rights and welfare.

The research will be performed according to ethical principles and in compliance with all federal,
      state and local laws, as well as institutional regulations and policies regarding the protection of  
      human subjects.

All members of the research team will be kept apprised of research goals.

I will obtain approval for this research study and any subsequent revisions prior to my initiating the
      study or any change and I will obtain continuing approval of this study prior to the expiration date     
      of any approval period.

I will report to the HIC any serious injuries and/or other unanticipated problems involving risk to
      participants.

I am in compliance with the requirements set by the University and qualify to serve as the
      principal investigator of this project or have acquired the appropriate approval from the 
      Dean’s Office or Office of the Provost, or the Human Subject Protection Administrator at
      Yale-New Haven Hospital, or have a faculty advisor.

I will identify a qualified successor should I cease my role as principal investigator and facilitate a
smooth transfer of investigator responsibilities.
_____
 
PI Name (PRINT) and Signature
Date
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Department Chair’s Assurance Statement
Do you know of any real or apparent institutional conflict of interest (e.g., Yale ownership of a
sponsoring company, patents, licensure) associated with this research project?
 Yes (provide a description of that interest in a separate letter addressed to the HIC.)
 No
As Chair, do you have any real or apparent protocol-specific conflict of interest between yourself and
the sponsor of the research project, or its competitor or any interest in any intervention and/or method
tested in the project that might compromise this research project?
Yes (provide a description of that interest in a separate letter addressed to the HIC)
No
I assure the HIC that the principal investigator and all members of the research team are qualified by
education, training, licensure and/or experience to assume participation in the conduct of this research
trial. I also assure that the principal investigator has departmental support and sufficient resources to
conduct this trial appropriately.
   ____________________________
   Chair Name (PRINT) and Signature  
    
 Date
   _________________________________
   Department
As the faculty advisor of this research project, I certify that:

The information provided in this application is complete and accurate.

This project has scientific value and merit and that the student or trainee investigator has the 
      necessary resources to complete the project and achieve the aims.

I will train the student investigator in matters of appropriate research compliance, protection of
      human subjects and proper conduct of research.

The research will be performed according to ethical principles and in compliance with all federal,
      state and local laws, as well as institutional regulations and policies regarding the protection of  
      human subjects.

The student investigator will obtain approval for this research study and any subsequent revisions
      Prior to initiating the study or revision and will obtain continuing approval prior to the expiration
      of any approval period.

The student investigator will report to the HIC any serious injuries and/or other unanticipated 
      problems involving risk to participants. 

I am in compliance with the requirements set forth by the University and qualify to serve as
      the faculty advisor of this project.
___________
______
_____
    Advisor Name (PRINT) and Signature
Date
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YNHH Human Subjects Protection Administrator Assurance Statement
Required when the study is conducted solely at YNHH by YNHH health care providers.
As Human Subject Protection Administrator (HSPA) for YNHH, I certify that:

I have read a copy of the protocol and approve it being conducted at YNHH.

I agree to notify the IRB if I am aware of any real or apparent institutional conflict of interest.

The principal investigator of this study is qualified to serve as P.I. and has the support of the hospital 
for this research project.
  ______________________________________
    YNHH HSPA Name (PRINT) and Signature       
Date
For HIC Use Only
Date Approved
Human Investigation Committee Signature
This protocol is valid through ______________________________________________
SECTION V: RESEARCH PLAN
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested. 
To investigate whether the daily glucose profiles as assessed by continuous glucose monitoring 
for 1 week of normal weight, obese, and diabetic individuals relate to hunger levels and food 
intake.
2. Background: Describe the background information that led to the plan for this project. 
Provide references to support the expectation of obtaining useful scientific data.
The rising incidence of type 2 diabetes (T2DM) and obesity has paralleled the increased 
consumption of sugar, which has been associated with numerous adverse metabolic effects 
including weight gain, insulin resistance, cognitive decline, and stroke 1-3.
Human studies using nuclear magnetic resonance spectroscopy (MRS), a powerful, non-invasive 
tool to determine the concentration of metabolites in living tissue, have shown that glucose 
transport across the BBB is not rate limiting during hyperglycemia 4,5. Furthermore, in previous 
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work from our lab, brain glucose levels remain elevated in chronically hyperglycemic diabetic 
rats suggesting that there is very limited protective adaptation by the BBB 6. We have also shown 
using microdialysis probes and hyperglycemic clamp in human subjects undergoing 
electrophysiological evaluation for epilepsy that brain microdialysate from non-epileptogenic 
brain areas showed a 200% rise in glucose levels from baseline during a hyperglycemic clamp 7. 
Glucose has traditionally been considered a satiety signal in the brain. More than 50 years ago, 
Jean Mayer proposed the glucostatic theory of feeding where elevated glucose levels act as a 
satiety signal in the brain while falling glucose levels exert the opposite effect to stimulate 
hunger and subsequent food consumption 8-12. While our knowledge of the signals from the 
periphery to the brain that regulate eating behavior has expanded exponentially, much remains 
unknown about the mechanisms by which glucose regulates feeding behavior and how these 
pathways are altered in diabetes and obesity. 
Furthermore, previous published data from our lab13, subjects using a 2-step clamp, i.e. 
euglycemia (~90 mg/dL) followed by mild hypoglycemia (~65 mg/dL) in conjunction with fMRI 
and visual stimuli of food/non-food, showed that euglycemia was associated with activation of 
prefrontal cortex (PFC) and anterior cingulate (p<0.05), while during hypoglycemia there was 
activation of hypothalamus, nucleus accumbens, insula, caudate and putamen in response to 
visual food cues (p<0.05). In addition, hunger was increased during hypoglycemia as compared 
to the euglycemic phase (5.7 ± 0.5 vs 4.5 ± 0.5; p<0.01). The study also included a small group 
of obese subjects (n=5). When this group was compared to lean subjects, they failed to show 
activation of the medial pre-frontal cortex during euglycemia and showed greater bilateral 
activation of the hypothalamus, striatum and insula in response to high-calorie food images 
during mild hypoglycemia (p <0.05). Taken together the data suggest that during euglycemic 
phase of the clamp study there was activation of PFC in lean individuals, a region involved in 
complex cognitive behaviors, decision making and moderating correct social behavior14, whereas 
during hypoglycemic phase limbic regions were activated; which are involved in physiological 
and emotional responses15. Of particular interest these preliminary data suggest that the neural 
response to food consumption and food cues is altered in obese individuals in a way that could 
contribute to overeating behavior, namely increased stimulation of reward centers in response to 
nutrients (glucose) and/or food cues. This differentiated brain response could be a contributing 
factor to the pathogenesis of human obesity. We also plan to study patients with diabetes, who 
have chronic high glucose levels.  Preliminary work from our group showed that obese unlike 
lean subjects suppressed activity in the ventral medial PFC (executive-control area) in response 
to food images; with a preferential liking/wanting for high-calorie food during hyperglycemia16.  
Therefore, we want to investigate if changes in circulating glucose levels can interfere with 
eating behavior and food intake in lean, obese subjects and patients with diabetes. 
Continuous glucose monitoring (CGM) is used in people with diabetes for better glycemic 
control as well as in non-diabetic individuals to characterize glucose patterns 17-19. No study thus 
far has looked into glucose profiles normal weight, obese, and diabetic individuals in a normal, 
outpatient setting in relation to hunger and food intake. In a preliminary study of 8 individuals 
who wore a CGMS for 1 week and recorded their food intake and hunger levels, we found that 
increasing subjective hunger levels are more related to pre-prandial glucose peaks as opposed to 
nadirs. Furthermore, declines in glucose are correlated with caloric intake as well as the 
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macronutrient content of subsequent meals. Our findings suggest that glycemic excursions 
following a meal may play a role in hunger and food choices for the subsequent meal.
3. Research Plan: Summarize the study design and research procedures using non-technical 
language that can be readily understood by someone outside the discipline. Be sure to 
distinguish between standard of care vs. research procedures when applicable, and include 
any flowcharts of visits specifying their individual times and lengths. Describe the setting in 
which the research will take place.
Continuous Glucose Monitoring System (CGMS): To evaluate the effect of blood glucose levels 
on eating behavior in a population of patients with diabetes in a free-living environment; we plan 
to study 15 lean healthy control subjects (BMI <25 kg/m2), 15 obese non-diabetic subjects (BMI 
> 30 kg/m2), 15 T2DM subjects who will be age and BMI-matched to obese, non-diabetic 
subjects, and 15 T1DM subjects who will be age and BMI matched to control, non-diabetic 
subjects. The participants will come to the research unit for a screening visit to review their 
medical history and receive a physical examination. Blood tests will be collected for exclusion of 
anemia (hematocrit), diabetes (A1c), untreated thyroid disease (TSH), or any other major health 
problems (liver enzymes and creatinine). The total amount of blood drawn will be less 1 table 
spoon. All female subjects will undergo a urine pregnancy test at the time of screening. These 
blood and urine tests will not be performed if they have been done within the 3 months prior to 
the screening visit. The participants who qualify will be invited to use the CGMS (DEXCOM G4 
Platinum) for up to 7 days. On the visit for placement of the CGMS: 1) the participants will be 
explained by one of the study physicians how to use a glucometer (FreeStyle or Accu-Check), 2) 
they will have the CGMS inserted under the skin, and 3) they will be instructed how to fill up the 
food log (using informational brochures). On the second visit (up to 7 days after the initial visit)  
the CGMS will be removed from the skin and the glucose meter and food log will be returned to 
the investigators. The first visit will last approximately 1 hour and the second visit about 30 
minutes. The CGMS consists of 3 parts: sensor, transmitter and monitor. The small sensor 
measures the glucose levels from the interstitial tissue. The transmitter is attached on top of the 
sensor and connects wirelessly to the monitor. The sensor is sterile and comes in an unopened 
package. It has a plastic wire-like tip that is placed under the skin and continuously measures the 
glucose levels. One of the study physicians will insert the CGMS wire-like tip under the 
volunteer’s skin with the use of the DEXCOM sensor insertion kit. The transmitter is snapped to 
the sensor pod and the sensor/transmitter unit will be attached to the skin with an adhesive patch. 
The monitor is the size of a small hand-held device with a digital screen that displays a graph 
showing the glucose levels from the previous 4-24 hours. While using the CGMS, the volunteers 
will need to check their glucose levels with a glucose meter twice a day to calibrate the device. 
One of the investigators will teach the volunteers how to use the glucose meter, which will be 
loaned to the volunteers during the CGMS session. The monitor and transmitter should be kept 6 
meters apart for adequate wireless communication. While using the CGMS the participants will 
be asked to fill up a food record. The Food Record will ask about amount and type of food 
consumed throughout the day. The participants will also register how hungry they are before the 
meal and how full they feel after they ate, and type and duration of physical activity After 
completing the CGMS session, the sensor will be removed by one of the investigators. To 
remove the sensor, the adhesive patch will be gently peeled off from the skin, together with the 
sensor pod and transmitter. Removal of the sensor is a painless procedure. The sensor and sensor 
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pod will be discarded after use. The transmitter and receiver and glucose meter will be 
disinfected with a bleach solution and 70% isopropyl alcohol wipes to remove any disinfectant 
residue.
.
4. Genetic Testing   N/A 
A. Describe
i.
the types of future research to be conducted using the materials, specifying if 
immortalization of cell lines, whole exome or genome sequencing, genome wide 
association studies, or animal studies are planned
ii. the plan for the collection of material or the conditions under which material will 
be received
iii. the types of information about the donor/individual contributors that will be 
entered into a database
iv. the methods to uphold confidentiality
B. What are the conditions or procedures for sharing of materials and/or distributing for 
future research projects?
C. Is widespread sharing of materials planned?
D. When and under what conditions will materials be stripped of all identifiers?
E. Can donor-subjects withdraw their materials at any time, and/or withdraw the identifiers 
that connect them to their materials?
i.
How will requests to withdraw materials be handled (e.g., material no longer 
identified: that is, anonymized) or material destroyed)?
F. Describe the provisions for protection of participant privacy
G. Describe the methods for the security of storage and sharing of materials 
5. Subject Population: Provide a detailed description of the types of human subjects who will 
be recruited into this study.
15 lean, healthy control subjects (BMI <25 kg/m2)
15 obese, non diabetic subjects (BMI > 30 kg/m2)
15 T2DM subjects who will be age and BMI-matched to obese, non-diabetic subjects
15 T1DM subjects who will be age and BMI matched to control, non-diabetic subjects.
6. Subject classification: Check off all classifications of subjects that will be specifically 
recruited for enrollment in the research project. Will subjects who may require additional 
safeguards or other considerations be enrolled in the study? If so, identify the population of 
subjects requiring special safeguards and provide a justification for their involvement.
 Children
 Healthy 
Fetal material, placenta, or dead fetus
 Non-English Speaking
 Prisoners
 Economically disadvantaged persons
 Decisionally Impaired
 Employees
 Pregnant women and/or fetuses
 Yale Students 
Females of childbearing potential
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NOTE: Is this research proposal designed to enroll children who are wards of the state as 
potential subjects? 
 Yes  
 No (If yes, see Instructions section VII #4 for further 
requirements)
7. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or    
exclusion?
Inclusion criteria (for both diabetic and non-diabetic participants):
-Age 18-65 years
- A1c < 10.5 %
Exclusion criteria:
BMI <18 (no upper limit), Creatinine > 1.5 mg/dL, Hgb < 10 mg/dL, ALT > 2.5 X ULN, untreated 
thyroid disease, uncontrolled hypertension, known neurological disorders, untreated psychiatric 
disorders, use of antidepressants and psychiatric medications, use of weight loss medications in the 6 
months prior to the study, malignancy, smoking, current or recent steroid use in last 3 months, history 
of current illicit drug use; for women: pregnancy, or breastfeeding.
8. How will eligibility be determined, and by whom? 
Eligibility will be determined by a qualified physician associated with the research protocol 
and will be based upon the above inclusion/exclusion criteria 
9. Risks: Describe the reasonably foreseeable risks, including risks to subject privacy, 
discomforts, or inconveniences associated with subjects participating in the research. 
The CGMS poses no major risks to the subjects. Participants may feel a mild discomfort (pin 
prick sensation) during the sensor insertion.  Some individuals may experience black and 
blueness of the skin at the insertion site of the CGMS sensor, which resolves by itself in a 
few days. Redness and discomfort (inflammation) can occur at the sensor insertion site. 
Rarely sensors may fracture and a small piece may remain under the skin which will need to 
be removed by the physician.  This may cause mild discomfort, bruising, or temporary 
bleeding.
Blood samples will be obtained with a needle inserted into a vein which results in mild 
discomfort, bruising and temporary bleeding.
10. Minimizing Risks: Describe the manner in which the above-mentioned risks will be 
minimized.
CGMS catheter will be placed under sterile conditions by experienced staff members. In case 
of signs of inflammation or bruise at the sensor insertion site, the sensor will need to be 
removed immediately and standard care should be applied.  The participants will be given 
one of the study physician’s cell phone number to contact for any questions, concerns or 
problems.
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11. Data and Safety Monitoring Plan: Include an appropriate Data and Safety Monitoring Plan 
(DSMP) based on the investigator’s risk assessment stated below. (Note: the HIC will make 
the final determination of the risk to subjects.) For more information, see the Instructions, 
page 24.
a. 
What is the investigator’s assessment of the overall risk level for subjects 
participating in this study? greater to minimal risk
b.
If children are involved, what is the investigator’s assessment of the overall risk 
level for the children participating in this study? 
c.
Copy, paste, and then tailor an appropriate Data and Safety Monitoring Plan 
from  http://www.yale.edu/hrpp/forms-templates/biomedical.html  for
i. Minimal risk
ii. Greater than minimal/moderate risk
iii. High risk
Greater Than Minimal Risk DSMP
1. Personnel responsible for the safety review and its frequency:
The principal investigator will be responsible for monitoring the data, assuring protocol 
compliance, and conducting the safety reviews at the specified frequency, which must be 
conducted at a minimum of every 6 months (including when reapproval of the protocol is 
sought).  During the review process, the principal investigator (monitor) will evaluate whether 
the study should continue unchanged, require modification/amendment, or close to enrollment. 
Either the principal investigator, the IRB or [enter the names of other oversight bodies that have 
this authority, e.g., Yale Cancer Center Data and Safety Monitoring Committee (DSMC)] have 
the authority to stop or suspend the study or require modifications.
2. The risks associated with the current study are deemed greater than minimal for the 
following reasons: (choose those that apply)
1. We do not view the risks associated with the CGM and Glucose monitoring __________ 
as minimal risks.
Although we have assessed the proposed study as one of greater than minimal risk, the potential 
exists for anticipated and/or unanticipated adverse events, serious or otherwise, to occur since it 
is not possible to predict with certainty the absolute risk in any given individual or in advance of 
first-hand experience with the proposed study methods. Therefore, we provide a plan for 
monitoring the data and safety of the proposed study as follows:
3. Attribution of Adverse Events:
Adverse events will be monitored for each subject participating in the study and attributed to the 
study procedures / design by the principal investigator (Insert Investigator Name) according to 
the following categories:
a.) Definite: Adverse event is clearly related to investigational procedures(s)/agent(s).
b.) Probable: Adverse event is likely related to investigational procedures(s)/agent(s).
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c.) Possible: Adverse event may be related to investigational procedures(s)/agent(s).
d.) Unlikely: Adverse event is likely not to be related to the investigational 
procedures(s)/agent(s).
e.) Unrelated: Adverse event is clearly not related to investigational procedures(s)/agent(s).
4. Plan for Grading Adverse Events:
The following scale will be used in grading the severity of adverse events noted during the study:
1. Mild adverse event
2. Moderate adverse event
3. Severe 
5. Plan for Determining Seriousness of Adverse Events:
Serious Adverse Events:
In addition to grading the adverse event, the PI will determine whether the adverse event meets 
the criteria for a Serious Adverse Event (SAE).  An adverse event is considered serious if it 
results in any of the following outcomes:
1. Death;
2. A life-threatening experience in-patient hospitalization or prolongation of existing 
hospitalization; 
3. A persistent or significant disability or incapacity; 
4. A congenital anomaly or birth defect; OR
5. Any other adverse event that, based upon appropriate medical judgment, may jeopardize 
the subject’s health and may require medical or surgical intervention to prevent one of 
the other outcomes listed in this definition. 
An adverse event may be graded as severe but still not meet the criteria for a Serious Adverse 
Event.  Similarly, an adverse event may be graded as moderate but still meet the criteria for an 
SAE.  It is important for the PI to consider the grade of the event as well as its “seriousness” 
when determining whether reporting to the IRB is necessary.
6. Plan for reporting UPIRSOs (including Adverse Events) to the IRB
The principal investigator will report the following types of events to the IRB: 
Any incident, experience or outcome that meets ALL 3 of the following criteria:
1. Is unexpected (in terms of nature, specificity, severity, or frequency) given (a) the 
research procedures described in the protocol-related documents, such as the IRB-
approved protocol and informed consent document and (b) the characteristics of the 
subject population being studied; AND 
2. Is related or possibly related to participation in the research (possibly related means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); AND
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3. Suggests that the research places subjects or others at greater risk of harm (including 
physical, psychological, economic, legal, or social harm) than was previously known 
or recognized.
Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs) may be medical or 
non-medical in nature, and include – but are not limited to – serious, unexpected, and related 
adverse events and unanticipated adverse device effects.  Please note that adverse events are 
reportable to the IRB as UPIRSOs only if they meet all 3 criteria listed above.
These UPIRSOs/SAEs will be reported to the IRB in accordance with IRB Policy 710, using the 
appropriate forms found on the website. All related events involving risk but not meeting the 
prompt reporting requirements described in IRB Policy 710 should be reported to the IRB in 
summary form at the time of continuing review. If appropriate, such summary may be a simple 
brief statement that events have occurred at the expected frequency and level of severity as 
previously documented.  In lieu of a summary of external events, a current DSMB report can be 
submitted for research studies that are subject to oversight by a DSMB (or other monitoring 
entity that is monitoring the study on behalf of an industry sponsor).
7. Plan for reporting adverse events to co-investigators on the study, as appropriate the 
protocol’s research monitor(s), e.g., industrial sponsor, Yale Cancer Center Data and 
Safety Monitoring Committee (DSMC), Protocol Review Committee (PRC), DSMBs, study 
sponsors, funding and regulatory agencies, and regulatory and decision-making bodies.
For the current study, the following individuals, funding, and/or regulatory agencies will be 
notified (choose those that apply):
x All Co-Investigators listed on the protocol.
□ Yale Cancer Center Data and Safety Monitoring Committee (DSMC)
□ National Institutes of Health
□ Food and Drug Administration (Physician-Sponsored IND #_______)
□ Medical Research Foundation (Grant______)
□ Study Sponsor
□ Other Data Safety Monitoring Board (DSMB) or Committee (DSMC)
The principal investigator (Insert Investigator Name) will conduct a review of all adverse events 
upon completion of every study subject. The principal investigator will evaluate the frequency 
and severity of the adverse events and determine if modifications to the protocol or consent form 
are required.
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Please note: For any study that may be considered high risk, the IRB will be more focused on the 
safety requirements for the study and a DSMB will likely be required. 
For more guidance on Adverse Event reporting and DSMPs, see IRB Policy 710 Reporting 
Unanticipated Problems Involving Risks to Subjects or Others, including Adverse Events
The principal investigator is responsible for monitoring the data, assuring protocol 
compliance, and conducting the safety reviews at the specified frequency [e.g., monthly, 
quarterly, etc].  During the review process the principal investigator will evaluate whether 
the study should continue unchanged, require modification/amendment, or close to 
enrollment.
The principal investigator or the Institutional Review Board (IRB) have the authority to stop 
or suspend the study or require modifications.
.
d. For multi-site studies for which the Yale PI serves as the lead investigator: N/A
i. How will adverse events and unanticipated problems involving risks to subjects or 
others be reported, reviewed and managed?
ii. What provisions are in place for management of interim results?
iii. What will the multi-site process be for protocol modifications?
12. Statistical Considerations: Describe the statistical analyses that support the study design. 
This is a pilot project.  We estimate that a sample size of 15 subjects per group will provide 80% 
power to detect within group differences of of 1.1 standard deviations.  For changes in hunger 
ratings of liking, wanting and hunger we will have at least 80% power to detect between group 
differences across all glycemic conditions (i.e. main effect of group) of 1.0 standard deviation 
and within each condition of 1.25 standard deviations.
SECTION VI: RESEARCH INVOLVING DRUGS, BIOLOGICS, RADIOTRACERS, PLACEBOS AND 
DEVICES
N/A
A.  DRUGS, BIOLOGICS and RADIOTRACERS
1. Identification of Drug, Biologic or Radiotracer: What is (are) the name(s) of the drug(s) 
biologic(s)  or radiotracer(s) being used? Identify whether FDA approval has been granted and for 
what indication(s). 
All protocols which utilize a drug, biologic or radiotracer not approved by, but regulated by, the FDA, 
or a radiotracer regulated by the RDRC, must provide the following information:  
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a. What is the Investigational New Drug (IND) number assigned by the FDA?
b. Who holds the IND? 
c. All protocols which utilize a radiotracer not approved by, but regulated by the FDA must 
provide the IND number: _______________
Alternatively, use of the investigational radiotracer may be under RDRC/RSC oversight: (check 
if appropriate)_____________
For all investigational radiotracers, attach a copy of the RDRC/RSC application (for 
radioisotopes used in the PET Center, PET Center personnel may complete this step)
Go to http://rsc.med.yale.edu/login.asp?url=myApps.asp.  When you have logged in, complete 
the application and attach a copy to this submission.     
Alternatively, an exemption from IND filing requirements may be sought for a clinical
 investigation of a drug product that is lawfully marketed in the United States. If there is no IND and
 an exemption is being sought, review the following categories and complete the category that applies
 (and delete the inapplicable categories):
Exempt Category 1
The clinical investigation of a drug product that is lawfully marketed in the United States can be
exempt from IND regulations if all of the following are yes:
i.   The intention of the investigation is NOT to report to the FDA as a well-controlled study in support
     of a new indication for use or to be used to support any other significant change in the labeling for
     the drug.  
 Yes  
 No
ii. The drug that is undergoing investigation is lawfully marketed as a prescription drug product, and
      the intention of the investigation is NOT to support a significant change in the advertising for the
      product. 
 Yes  
 No
iii.  The investigation does NOT involve a route of administration or dosage level or use in populations
      or other factor that significantly increases the risks (or decreases the acceptability of the risks)   
      associated with the use of the drug product. 
 Yes  
 No
iv. The investigation will be conducted in compliance with the requirements for institutional (HIC)   
      review and with the requirements for informed consent of the FDA regulations (21 CFR Part 50  
and 21 CFR Part 56). 
 Yes  
 No
v.   The investigation will be conducted in compliance with the requirements regarding promotion and 
charging for investigational drugs. 
 Yes  
 No
Exempt Category 2 (all items i, ii, and iii must be checked to grant a category 2 exemption)
 i. The clinical investigation is for an in vitro diagnostic biological product that involves one or
more of the following (check all that apply):
 Blood grouping serum
 Reagent red blood cells 
 Anti-human globulin
 ii. The diagnostic test is intended to be used in a diagnostic procedure that confirms the
diagnosis made by another, medically established, diagnostic product or procedure; and
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 iii. The diagnostic test is shipped in compliance with 21 CFR §312.160.
Exempt Category 3
 The drug is intended solely for tests in vitro or in laboratory research animals if shipped in 
accordance with 21 CFR 312.60
Exempt Category 4
 A clinical investigation involving use of a placebo if the investigation does not otherwise 
require submission of an IND.
2. Background Information: Provide a description of previous human use, known risks, and data 
addressing dosage(s), interval(s), route(s) of administration, and any other factors that might 
influence risks. If this is the first time this drug is being administered to humans, include relevant 
data on animal models. 
3. Source: a) Identify the source of the drug or biologic to be used. 
b) Is the drug provided free of charge to subjects? 
 Yes  
 No
    If yes, by whom? 
4. Storage, Preparation and Use: Describe the method of storage, preparation, stability information, 
and for parenteral products, method of sterilization and method of testing sterility and 
pyrogenicity. 
Check applicable Investigational Drug Service utilized:
     
   YNHH IDS                                                                      
   Yale Cancer Center 
     
   CMHC Pharmacy                                                          
  West Haven VA
     
   PET Center                                                     
    None      
     
    Other: 
Note: If the YNHH IDS (or comparable service at CMHC or WHVA) will not be utilized, explain in 
detail how the PI will oversee these aspects of drug accountability, storage, and preparation.  
  
5. Use of Placebo: 
 Not applicable to this research project
If use of a placebo is planned, provide a justification which addresses the following:
a.
Describe the safety and efficacy of other available therapies. If there are no other
available therapies, state this.
b.   State the maximum total length of time a participant may receive placebo while on the study. 
c.   Address the greatest potential harm that may come to a participant as a result of  receiving    
  
   placebo. 
d.   Describe the procedures that are in place to safeguard participants receiving placebo. 
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6. Use of Controlled Substances:
Will this research project involve the use of controlled substances in human subjects?
 Yes  
 No See HIC Application Instructions to view controlled substance listings. 
If yes, is the use of the controlled substance considered:
 Therapeutic: The use of the controlled substance, within the context of the research, has the 
potential to benefit the research participant.
 Non-Therapeutic: Note, the use of a controlled substance in a non-therapeutic research study 
involving human subjects may require that the investigator obtain a Laboratory Research License. 
Examples include controlled substances used for basic imaging, observation or biochemical 
studies or other non-therapeutic purposes. See Instructions for further information.
7. Continuation of Drug Therapy After Study Closure   
 Not applicable to this project
Are subjects provided the opportunity to continue to receive the study drug(s) after the study has 
ended?
 
 Yes   If yes, describe the conditions under which continued access to study drug(s) may apply 
as well as conditions for termination of such access. 
 
 No    If no, explain why this is acceptable.
 B.  DEVICES
1. Are there any investigational devices used or investigational procedures performed at YNHH, e.g., 
YNHH Operating Room or YNHH Heart and Vascular Center?  Yes 
  No 
If Yes, please be aware of the following requirements:
a.
A YNHH New Product/Trial Request Form must be completed;  
b. Your request must be reviewed and approved by a Hospital Committee before 
patients may be scheduled; and  
c.
The notice of approval from YNHH must be submitted to the HIC for the protocol 
file. 
Please contact Gina D’Agostino, gina.d’agostino@ynhh.org or 203-688-5052, to initiate the 
process. 
2. What is the name of the device to be studied in this protocol?
Has this device been FDA approved? 
 Yes  
 No
If yes, state for what indication.
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3. Background Information: Provide a description of previous human use, known risks, and any 
other factors that might influence risks. If this is the first time this device is being used in humans, 
include relevant data on animal models. 
4. Source: 
a) Identify the source of the device to be used. 
b) Is the device provided free of charge to subjects? 
 Yes  
 No
5. What is the PI’s assessment of risk level (significant or non-significant) associated with the use of 
the device? 
 Significant Risk (SR) Device Study: A study of a device that presents a potential for serious 
risk to the health, safety, or welfare of a participant and 1) is intended as an implant; 2) is used in 
supporting or sustaining human life; or otherwise prevents impairment of human health; 3) is of 
substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise prevents 
impairment of human health; or 4) otherwise presents a potential for serious risk to the health, 
safety, or welfare of a participant.   
Significant Risk Devices require an Investigational Device Exemption (IDE) issued by the FDA.
What is the IDE number assigned by the FDA? 
Did the FDA approve this IDE as Category A (experimental/investigational) or as Category B 
(non-experimental/investigational)?
Who holds the IDE?
 Non-Significant Risk (NSR) Device Study: A study of a device that does not meet the   
definition for a significant risk device and does not present a potential for serious risk to the health, 
safety, or welfare of participants.  Note that if the HIC concurs with this determination, an IDE is 
not required.
6.  Abbreviated IDE or Exempt IDE: There are abbreviated requirements for an IDE and there also 
are exemptions to the requirement for an IDE.  See the criteria in the HIC Application Instructions, 
Section VI.B.4 at 
http://www.yale.edu/hrpp/resources/docs/100FR1aHICProtocol_Application_Instructions5-25-
11.pdf to determine if these pertain to this study.
  
 Abbreviated IDE or Exempt IDE – If criteria set forth in the HIC Application Instructions 
are met, copy and paste the completed relevant section from the Instructions into this application.
7.   Investigational device accountability:
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a.
State how the PI, or named designee, ensures that an investigational device is 
used only in accordance with the research protocol approved by the HIC, and 
maintains control of the investigational device as follows:
Maintains appropriate records, including receipt of shipment, inventory at the 
site, dispensation or use by each participant, and final disposition and/or the return of the 
investigational device (or other disposal if applicable):
Documents pertinent information assigned to the investigational device (e.g., date, quantity, batch 
or serial number, expiration date if applicable, and unique code number):
Stores the investigational device according to the manufacturer's recommendations with respect to 
temperature, humidity, lighting, and other environmental considerations:
Ensures that the device is stored in a secure area with limited access in accordance with applicable 
regulatory requirements:
Distributes the investigational device to subjects enrolled in the IRB-approved protocol:
SECTION VII: RECRUITMENT/CONSENT AND ASSENT PROCEDURES 
1.
Targeted Enrollment: Give the number of subjects:
a.  targeted for enrollment at Yale for this protocol__60_
b.    If this is a multi-site study, give the total number of subjects targeted across all 
sites___ 
2.
Indicate recruitment methods below.  Attach copies of any recruitment materials that will 
be used.
 Flyers
 Internet/Web Postings
 Radio
 Posters
 Mass E-mail Solicitation
 Telephone
 Letter
 
 Departmental/Center Website
 Television
 Medical Record Review
 Departmental/Center Research Boards
 Newspaper
 Departmental/Center Newsletters
 Web-Based Clinical Trial Registries
  YCCI Recruitment database
 Clinicaltrials.gov Registry (do not send materials to HIC)
 Other (describe): Yale Diabetes Registry (HIC# 0911005973)
3.
 Recruitment Procedures: 
a.Describe how potential subjects will be identified.
Subjects will be recruited by flyers that will be posted locally. The flyer will display the contact 
information of the study team. They may also be identified at the Adult Endocrine Clinic and Yale 
University Health Services and approached through their caregiver. In addition the diabetes registry 
will be used to identify eligible patients and contact them by phone or letter, since this category of 
patients have already given their consent to be contacted for potential trials. Furthermore, they will be 
recruited through YCCI website, ClinicalTrials.gov website and community clinics. They will then be 
offered to contact one of the research team members or if they give their approval, to be contacted by 
the team by phone or e-mail and they will provide the subject with additional information about the 
study and the investigator will determine the eligibility of the subject for the study. The purpose and 
potential complications of the study will be explained to each subject in detail. 
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During the screening session, the informed consent form and study details are reviewed in detail by 
one of the project investigators and the subject will be asked to read the informed consent form 
(approved by the Yale Human Investigations committee). The subject will be given time to ask 
questions and only after that will the subject be asked to give informed consent to participate. The 
informed consent form and study details will again be reviewed with the subject on each study day 
prior to beginning the study.
b.Describe how potential subjects are contacted. 
The consent process is a two-step process, whereby the subject initiates contact via telephone or in 
person presentation and will undergo a phone or in person screen with a member of the research team. 
Thereafter, potentially eligible candidates will be scheduled for a face-to-face interview. 
c.Who is recruiting potential subjects? See IRES IRB
4.
Screening Procedures
a.Will email or telephone correspondence be used to screen potential subjects for eligibility 
prior to the potential subject coming to the research office? 
 Yes  
 No
b. If yes, identify below all health information to be collected as part of screening and 
check off any of the following HIPAA identifiers to be collected and retained by the 
research team during this screening process. 
HEALTH INFORMATION TO BE COLLECTED:
 
HIPAA identifiers: 
 Names 
 All geographic subdivisions smaller than a State, including: street address, city, county, precinct, zip codes and their 
equivalent geocodes, except for the initial three digits of a zip code if, according to the current publicly-available data from 
the Bureau of the Census: (1) the geographic unit formed by combining all zip codes with the same three initial digits 
contains more than 20,000 people, and (2) the initial three digits of a zip code for all such geographic units containing 
20,000 or fewer people is changed to 000. 
  Telephone numbers
 Fax numbers 
 E-mail addresses
 Social Security numbers 
 Medical record numbers
 Health plan beneficiary numbers 
 Account numbers 
  All elements of dates (except year) for dates related to an individual, including: birth date, admission date, discharge 
date, date of death, all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages 
and elements may be aggregated into a single category of age 90 or older 
 Certificate/license numbers 
 Vehicle identifiers and serial numbers, including license plate numbers 
 Device identifiers and serial numbers 
 Web Universal Resource Locators (URLs) 
 Internet Protocol (IP) address numbers 
 Biometric identifiers, including finger and voice prints 
 Full face photographic images and any comparable images 
 Any other unique identifying numbers, characteristics, or codes 
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5.
Assessment of Current Health Provider Relationship for HIPAA Consideration:
Does the Investigator or any member of the research team have a direct existing clinical 
relationship with any potential subject? 
 Yes, all subjects
 Yes, some of the subjects
 No
If yes, describe the nature of this relationship.
An investigator may be the treating clinician for subjects recruited from the Endocrine Clinic.
6.
Request for waiver of HIPAA authorization: (When requesting a waiver of HIPAA 
Authorization for either the entire study, or for recruitment purposes only.  Note: if you are collecting 
PHI as part of a phone or email screen, you must request a HIPAA waiver for recruitment purposes.)
Choose one: For entire study: ______ For recruitment purposes only: __X____
i. Describe why it would be impracticable to obtain the subject’s authorization for 
use/disclosure of this data;
We will need the volunteers’ full name, address, date of birth, and phone numbers to 
schedule a screening visit at the Hospital Research Unit. We also would like to be 
able to review clinic appointments to see if any of the scheduled patients meet the 
inclusion criteria prior to calling them on the phone. This would include reviewing 
their diagnosis for DM, their age to be between 18-65 years, and their Body Mass 
Index (BMI). By reviewing this information prior to contact, we will be able to avoid 
contacting subjects that may not be included due to BMI and age.
ii. If requesting a waiver of signed authorization, describe why it would be 
impracticable to obtain the subject’s signed authorization for use/disclosure of this 
data;
By signing this protocol application, the investigator assures that the protected 
health information for which a Waiver of Authorization has been requested will not 
be reused or disclosed to any person or entity other than those listed in this 
application, except as required by law, for authorized oversight of this research 
study, or as specifically approved for use in another study by an IRB.
Researchers are reminded that unauthorized disclosures of PHI to individuals outside of the Yale 
HIPAA-Covered entity must be accounted for in the “accounting for disclosures log”, by subject 
name, purpose, date, recipients, and a description of information provided.  Logs are to be 
forwarded to the Deputy HIPAA Privacy Officer.
7. Required HIPAA Authorization: If the research involves the creation, use or disclosure of 
protected health information (PHI), separate subject authorization is required under the 
HIPAA Privacy Rule. Indicate which of the following forms are being provided:
 Compound Consent and Authorization form
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 HIPAA Research Authorization Form
8. Process of Consent/Assent: Describe the setting and conditions under which consent/assent will 
be obtained, including parental permission or surrogate permission and the steps taken to ensure 
subjects’ independent decision-making. 
The study will be described to the subject in detail, including the purpose and potential risks 
associated with the study. This will be explained by the physician, including the intervention and 
process for the study day. The subject will be required to read and sign the consent form 
approved by the HIC, and the patient will retain a copy of this consent to review. Additionally, 
the patient will have sufficient time to ask questions during the screening and will be encouraged 
to contact investigators with further questions or concerns. All subjects who will be asked to 
volunteer are informed that no immediate personal medical benefits will be derived from 
participation. Any subject who appears incapable of providing informed consent (e.g., due to 
apparent cognitive impairment) will be excluded. Subjects will be informed that they can decline 
to participate in the study without penalty, and given the opportunity to withdraw from the study 
prior to analysis of their data. All subjects will be given a copy of the consent form enclosed with 
this protocol outlining the risks and benefits of participation in this study. Following the 
resolution of any questions, the subjects will be asked to sign the consent form, if he/she agrees 
to participate.
9. Evaluation of Subject(s) Capacity to Provide Informed Consent/Assent: Indicate how the 
personnel obtaining consent will assess the potential subject’s ability and capacity to consent to the 
research being proposed. 
We do not plan to recruit subjects with limited decision-making capacity. Potential subjects will 
undergo a face-to-face interview.  At that time, a study physician will meet the subject, review 
the informed consent form, explain the purpose of the study and risks associated with 
participation, and will be available for questions. To ensure that the study subject understands the 
study, the subject will be asked questions about the study procedures and the risks associated 
with participation. If any concern arises that the study subject did not fully understand the study, 
the study physician may decide that the subject is not suitable for participation.  If the subject is 
still interested after all questions have been answered, a study physician will ask the subject to 
sign the informed consent form.
10. Documentation of Consent/Assent: Specify the documents that will be used during the 
consent/assent process. Copies of all documents should be appended to the protocol, in the same 
format that they will be given to subjects. 
There will be a specific Compound Consent and Authorization form.
11. Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for 
research involving non-English speaking subjects. Translated copies of all consent materials must 
be submitted for approval prior to use. 
N/A, we do not plan to recruit non-English speaking subjects.
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12. Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed consent, or 
a full waiver of consent, depending on the study. If you will request either a waiver of consent, 
or a waiver of signed consent for this study, complete the appropriate section below.  
 
 Not Requesting a consent waiver 
 
 Requesting a waiver of signed consent
       
 Requesting a full waiver of consent
   
A. Waiver of signed consent: (Verbal consent from subjects will be obtained. If PHI is 
collected, information in this section must match Section VII, Question 6)
 Requesting a waiver of signed consent for Recruitment/Screening only 
If requesting a waiver of signed consent, please address the following:
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No
b. Does a breach of confidentiality constitute the principal risk to subjects? 
 Yes  
 No
OR
c. Does the research activity pose greater than minimal risk? 
 Yes If you answered yes, stop. A waiver cannot be granted.  Please note: 
Recruitment/screening is generally a minimal risk research activity  
 No 
AND
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No
 Requesting a waiver of signed consent for the Entire Study (Note that an information 
sheet may be required.)
If requesting a waiver of signed consent, please address the following:
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No
b. Does a breach of confidentiality constitute the principal risk to subjects? 
 Yes  
 No
OR
c. Does the research pose greater than minimal risk? 
 Yes If you answered yes, stop. A 
waiver cannot be granted.    
 No 
AND
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No
B. Full waiver of consent: (No consent from subjects will be obtained for the activity.) 
 Requesting a waiver of consent for Recruitment/Screening only 
a. Does the research activity pose greater than minimal risk to subjects?  
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 Yes  If you answered yes, stop. A waiver cannot be granted. Please note: 
Recruitment/screening is generally a minimal risk research activity 
 No
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No
c. Why would the research be impracticable to conduct without the waiver? 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date? 
 Requesting a full waiver of consent for the Entire Study (Note: If PHI is 
collected, information here must match Section VII, question 6.)
If requesting a full waiver of consent, please address the following:
a. Does the research pose greater than minimal risk to subjects?  
 Yes  If you answered yes, stop. A waiver cannot be granted.  
 No
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No
c. Why would the research be impracticable to conduct without the waiver? 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date? 
SECTION VIII: PROTECTION OF RESEARCH SUBJECTS
    Confidentiality & Security of Data:
a.    What protected health information (medical information along with the HIPAA identifiers) 
about subjects will be collected and used for the research?   

 Name

Address

Phone number

Age

Medical record number

Race

Past medical, and surgical history, allergies, medications taken.

Family and social history

Body mass index, vital signs

Labs, including A1c, ALT/AST, creatinine, TSH, pregnancy test, and CGMS results
b. How will the research data be collected, recorded and stored? 
Research data will be collected directly from the subject as well as via the electronic medical 
record. Subjects will be assigned a study number. The principal investigator will create a 
computer worksheet where the name of the subject’s medical information is linked to the 
coded information.  This will be housed on a password protected computer on a secured 
network. Only the investigators will have access to the computer records, which include the 
subject's identity, in order to evaluate the information generated by the study.  No further 
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public disclosure of this information will be made. One copy of the consent form will be kept 
in a secured and locked cabinet in the PI’s office (which is also locked). The subject’s name 
will be kept separate from the results.
c.    How will the digital data be stored? 
 CD  
 DVD  
 Flash Drive  
 Portable Hard   
       Drive  
 Secured Server  
 Laptop Computer  
 Desktop Computer  
 Other
d.    What methods and procedures will be used to safeguard the confidentiality and security of    
the identifiable study data and the storage media indicated above during and after the 
subject’s participation in the study?
Do all portable devices contain encryption software? 
 Yes   
 No
         If no, see http://hipaa.yale.edu/guidance/policy.html
All identifiable subject information that is collected during recruitment, screening, and 
participation will appear only on the initial paper forms, which will be kept under lock and 
key in the academic office of one of the study investigators. All digital files that could link a 
code number to an individual study subject will be password protected and stored on CD, 
which will be kept locked in the PI’s office.
e.
What will be done with the data when the research is completed? Are there plans to destroy     
the identifiable data? If yes, describe how, by whom and when identifiers will be destroyed. 
If no, describe how the data and/or identifiers will be secured.
Procedures to ensure confidentiality follow the regulations and policies of the Yale 
University School of Medicine. The security mechanisms specified above in section d will 
continue to be in place to protect study data.
f.   Who will have access to the protected health information (such as the research sponsor, the  
investigator, the research staff, all research monitors, FDA, Yale Cancer Center Data and Safety 
Monitoring Committee (DSMC), SSC, etc.)? (please distinguish between PHI and de-identified 
data) 
The NIDDK will be the only external agency that will have access to de-identified study data. 
Only the investigators will have access to PHI and de-identified data. The Yale University HIC 
will have access to study files.
g.   If appropriate, has a Certificate of Confidentiality been obtained? N/A
h.   Are any of the study procedures likely to yield information subject to mandatory reporting   
requirements? (e.g. HIV testing – reporting of communicable diseases; parent interview -
incidents of child abuse, elderly abuse, etc.). Please verify to whom such instances will need to 
be reported. N/A
SECTION IX: POTENTIAL BENEFITS
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Potential Benefits: Identify any benefits that may be reasonably expected to result from the 
research, either to the subject(s) or to society at large. (Payment of subjects is not considered a 
benefit in this context of the risk benefit assessment.) 
Healthy non-diabetic subjects will have no direct benefit from the studies. Diabetic subjects will 
benefit by learning about their blood glucose levels while using the CGM.
         SECTION X: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS
1.     Alternatives: What other alternatives are available to the study subjects outside of the research?
The alternative is to decline participation in the study.
2. 
Payments for Participation (Economic Considerations): Describe any payments that will be 
made to subjects, the amount and schedule of payments, and the conditions for receiving this 
compensation. 
Participants will be paid $150 for using the CGM, upon completion of the study. Compensation 
may be provided in the form of check or through Bank of America card issued through YCCI. In 
addition parking will be complementary.
3.
Costs for Participation (Economic Considerations): Clearly describe the subject’s costs 
associated with participation in the research, and the interventions or procedures of the study that 
will be provided at no cost to subjects.    
There will be no additional cost to the study participants. 
4.
In Case of Injury: This section is required for any research involving more than minimal risk.
a.     Will medical treatment be available if research-related injury occurs? 
b.     Where and from whom may treatment be obtained? 
c.     Are there any limits to the treatment being provided? 
d.     Who will pay for this treatment? 
e.     How will the medical treatment be accessed by subjects? 
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