Clinical trial NCT03180489
Conditions: Weight Loss
Sponsor: Christopher Bell
Start date: 2017-05-03; Completion date: 2018-12-21
Enrollment: 62 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Dapagliflozin is a medicine to treat diabetes. Its mechanism of action is via sodium-glucose co-transporter 2 (SGLT2) inhibition. In adults with diabetes, use of sodium-glucose co-transporter 2 inhibitors is associated with moderate weight (fat) loss, in addition to other health benefits, including decreased blood pressure, decreased inflammation, and decreased oxidative stress. It is unclear as to whether these health benefits are due to SGLT2 inhibition per se, or as a secondary effect of weight loss. We wish to compare the health benefits of dietary counseling for weight loss with and without concomitant use of an SGLT2 inhibitor.

Detailed description:
This is a randomized, prospective, placebo-controlled, double blind, repeated measures study. 50 overweight/obese adults (body mas index \> 27.5 kg/m2) will be recruited for participation and randomly assigned to one of two 12 week treatments: (1) daily oral administration of Dapagliflozin with dietary counseling to promote weight loss; or, (2) daily oral administration of a placebo with dietary counseling to promote weight loss.

Arms: arm 1: Daily oral administration of dapagliflozin tablet with dietary counseling to promote weight loss. arm 2: Daily oral administration of placebo tablet with dietary counseling to promote weight loss.
Interventions: intervention 1: Dapagliflozin Tablet intervention 2: Placebo Tablet
Intervention descriptions: intervention 1: Daily oral administration of dapagliflozin with dietary counseling to promote weight loss. Dapagliflozin 5 mg tablet will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study. intervention 2: Daily administration of placebo tablet with dietary counseling to promote weight loss. Matching placebo for dapagliflozin 5 mg tablet will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study.

Protocol documents:
Prot_SAP_ICF_000.pdf: 
 
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For 
Weight Loss?  
 
NCT03180489 
Unique Protocol ID: 17-7147H 
22 March 2018 


 
NOTICE OF APPROVAL FOR HUMAN RESEARCH
DATE:
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Research Integrity & Compliance Review Office
Office of the Vice President for Research
321 General Services Building - Campus Delivery 2011 eprotocol
TEL: (970) 491-1553
FAX: (970) 491-2293
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Research Integrity & Compliance Review Office
Office of the Vice President for Research
321 General Services Building - Campus Delivery 2011 eprotocol
TEL: (970) 491-1553
FAX: (970) 491-2293
 


 
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Continuing review
1
Personnel Information
3
Subject Population
6
Study Location
7
General Checklist
7
Funding
9
Expedited Paragraphs
10
Purpose,Study Procedures,Background
12
Radioisotopes or Radiation Machines
19
Medical Equipment for Human Subjects and Laboratory Animals; Investigatiional Devices
20
Drugs, Reagents, or Chemicals
20
Subject Population (a-g)
21
Subject Population (h-m)
24
Risks
27
Benefits, Procedures to Maintain Confidentiality
32
Potential Conflict of Interest
33
Informed Consent
34
Assent Background
35
HIPAA
35
Attachments
37
Obligations
42


 
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Event History
43


Page 1 of 44
 
1
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
* * * Continuing review * * *
 
To renew your protocol: 1. Complete this one-page form; 2.  If necessary, update any sections of the protocol
that need to be updated for the upcoming year (e.g., change in personnel, location); 3. Electronically "sign" the
application by clicking in the check box on the bottom of the "Obligations" page; 4.  Remember to click "Submit
Form" and confirm your intent to submit by clicking "OK" so that the IRB administrators receive your application.
You must answer each question. Input N/A to answer any questions that are not applicable.  NOTE:  Documents
that contain much of the information required to answer the participant number questions below can be found in
the "Event History" section of each protocol.  The status on your homepage will be "Submitted to IRB" when your
submission is successful. IMPORTANT:   If the Department Head has changed since your last approval, please
be sure to update the Department Head listing on the personnel Information screen of your protocol.
 
1.
Summary: Number of Participants Associated with the Protocol: 
 
  
  
 a. 
Total number of participants approved to date:
We requested 60 overweight/obese adult volunteers (men and women) will be enrolled.  Please
see 1.e.
 
  
  
 b. 
Number of participants studied since the last approval date:
80
 
  
  
 c. 
Total number of participants studied since the beginning of the project:
80
 
  
  
 d. 
Number of participants remaining to study (total number of participants approved  LESS  the
total number of participants studied to date):
Please see 1.e.
 
  
  
 e. 
Please explain if there is a discrepancy in participant numbers (e.g., more participants
responded to a survey than had been approved):
We originally requested 60 overweight/obese adult volunteers (men and women) will be
enrolled.  Additionally it was stated in the protocol- “However, the number enrolled maybe
higher in the event of enrollment of replacement subjects for dropout(s) that discontinued for
reasons other than an adverse event due to study medication. In the event of a replacement
subject being enrolled, this subject will complete all visits”.
Please also note- the approval letter states approval for 50.  To clarify the above statement, as
a part of this continuing review we are amending the protocol to request recruitment of a total of


Page 2 of 44
 
2
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
200 individuals.
 
 
2.
 a. 
Reasons and number of withdrawals from the research (both subject and investigator initiated)
since the last approval date.
Declined participation:13
Non-compliance: 2
Screened out: 9
Moved to 14-5529H: 3
 
  
  
 b. 
Number of subjects lost to follow-up since the beginning of the study.
14
 
  
  
 c. 
Please summarize any protocol deviations/violations or unanticipated problems (UPs)/adverse
events (AEs) since the last continuing review or original approval (if this is your first continuing
review).  Please indicate if any of the unanticipated problems/events are being reported to the
IRB for the first time.  If you have or will make changes to your protocol as a result of any
unanticipated problem/event or adverse event, please summarize those changes in Question #5
below.
Please see adverse event log in the attachments.
Please see deviations:  Course of antibiotics was report verbally to IRB on 1/31/2018. Wrong
pill bottle 1st, Extended Invention Period, and Duration of invention are first time reports.
 
 
  
  
 e. 
Complaints about the research during the last year.
none
 
3.
A summary of any recent findings, literature, or other relevant information (especially pertaining to
risks), if applicable.
none
 
4.
Description of the remainder of project:
Y
Do you plan to recruit more subjects?
 
If "No," have all subjects completed all research-related interventions?  Note: Protocols must be
renewed to continue recruiting participants and/or collect data from already recruited participants.


Page 3 of 44
 
3
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
renewed to continue recruiting participants and/or collect data from already recruited participants.
 
N
Are you only performing data analysis?  NOTE:  If you are analyzing data with no identifiers (i.e., you
cannot link your data to individuals), you can close your protocol by submitting a Final Report.
 
N
Does this protocol have a Data Satety Monitoring Board (DSMB)?
 
If you do have a DSMB, have reports been submitted to the IRB and/or the Sponsor?
Upload any DSMB reports that have not yet been submitted to the IRB since the approval
or last continuing review.
 
5.
Summarize all approved changes in the protocol since the last continuing review or since the original
approval (if this is your first continuing review).  For example: Have you amended your protocol
during the past year?  Are you requesting to make any changes for the upcoming year?  Have you
included any changes as a result of an unanticipated problem/event or Adverse events (AE)?  Have
there been any personnel changes in the past year (including a change in department head)?
Amendment 1: Minor changes to include the description of the 3-day dietary recall record and
clarifications to counselling activities on visits 28 and 29 and nutritional counselor compliance
documentation was uploaded.
Amendment 2: Minor update to recruitment flyer.
Request amendment: As per deviation uploaded in the attachments, to allow for a 10 day course
(from 7 day course) of antibiotics.Antibiotics prescribed for any serious condition will be reviewed on
case by case basis no matter the course prescribed. As a part of this continuing review we are
amending the protocol to request recruitment of a total of 200 individuals.
 
         
If necessary, proceed to the appropriate section(s) of the protocol and make your requested changes.
Remember that if you are requesting to revise a document that is already attached, you must delete the
already attached document and upload the revised document.
 
6.  
List of Protocol Sections (and questions) that have been changed/modified.
Protocol and consent to allow for a 10 day course of antibiotics.
Added personnel- RICRO Please Add Elizabeth Thomson and Hayden Schoenberg to other key
research personnel, we don't have the option to add additional personnel.
Protocol to clarify request enrollment to 200.
---------------------------------------------------------------------------------------------
* * * Personnel Information * * *


Page 4 of 44
 
4
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
IMPORTANT NOTE: Mandatory Personnel on a protocol are: Principal Investigator and Department Head. Only
the Principal Investigator can submit the protocol; although other personnel listed on the protocol can create the
protocol. Human Subjects Protection Training is mandatory for Principal Investigator, Co-Principal Investigator,
and Key Personnel (as defined by NIH). Training must be updated every three (3) years.
 
Principal Investigator  Mandatory
Name of Principal Investigator
(Faculty, Staff or Postdoc)
Degree
Title
Bell, Christopher
Associate Professor
Email
Phone
Fax
Christopher.Bell@ColoState.EDU
(970) 491-7522
Department Name
Campus Delivery Code
 
Health and Exercise Science
1582
 
 Human Subjects Training Completed? PIs must complete training every three
(3) years.
Y
 
CO-Principal Investigator
Name of Co-Principal Investigator
(This could be another faculty or a
Master's or Ph.D. student)
Degree
Title
Melby, Chris
Professor
Email
Phone
Fax
Chris.Melby@colostate.edu
(970) 491-6736
Department Name
Campus Delivery Code
 
Food Science & Human Nutrition
 
 Human Subjects Training Completed? Training is required for Co-PI. Training
must be updated every three (3) years.
Y
No training data is available.
 
Additional Co-Principal Investigator
Name of Additional Co-Principal
Investigator
Degree
Title
Luckasen, Gary
MD
Medical Monitor


Page 5 of 44
 
5
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Email
Phone
Fax
gary.luckasen@uchealth.org
Department Name
Campus Delivery Code (CSU) or off-
campus mailing address
 
1582 Dept Hlth & Exer Sci
 
 Human Subjects Training Completed? Training is required for Co-PI.
Training must be updated every three (3) years.
Y
 
Department Head  Mandatory
Name of Department Head
Degree
Title
Braun, Barry
Professor
Email
Phone
Fax
Barry.Braun@colostate.edu
Department Name
Campus Delivery Code
 
Health and Exercise Science
 
 Human Subjects Training Completed?? Training is not required for
Department Head. Select "No" if you do not know if your Department Head has
completed training or not.
 
Administrative Contact
Name of Administrative Contact,
Project Director, or Lab Coordinator
Degree:
Title
Biela, Laurie
Research Associate III
Email
Phone
Fax
Laurie.Biela@colostate.edu
Department Name
Campus Delivery Code
 
Health and Exercise Science
 
 Human Subjects Training Completed? Training is not required for
Administrative Contacts
Y
No training data is available.
 
Other Researcher or Key Personnel


Page 6 of 44
 
6
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Name of Other Researcher (NOTE:
Anyone listed in this role will have
View Mode access only)
Degree
Title
Ackerman, Alissa
RA II - Integrative Biology Study
Coordinator
Email
Phone
Fax
Alissa.Ackerman@colostate.edu
Department Name
Campus Delivery Code (CSU) or off-
campus mailing address
 
1582 Dept Hlth & Exer Sci
1582
 
 Human Subjects Training Completed? Training is required for all Key
Personnel on NIH grants. Training must be updated every three (3) years.
Y
No training data is available.
---------------------------------------------------------------------------------------------
* * * Subject Population * * *
 
 
Subject Population(s) Checklist
        Â Select All That Apply - Note that this is your Targeted Population :
X
 Adult Volunteers
 Decisionally Challenged
Elderly
X
 Employees
 Fetuses
 Long-Term Patients
 Mentally Disabled
 Minors (under 18)
 Pregnant Women
 Prisoners
 Soldiers
X
 Students
 Other (i.e., non-English Speaking or any population that is not specified above)
       
---------------------------------------------------------------------------------------------


Page 7 of 44
 
7
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
* * * Study Location * * *
 
 
Study Location(s) Checklist
         Select All That Apply - NOTE: Check "Other" and input text: 1.) If your study location is not listed, or 2.) If
you would like to list details of your already-checked location (e.g., specific school within a school district)
Aims Community College
Colorado Department of Public Health & Environment
X
Colorado State University
Colorado State University - Pueblo Campus
Denver Public Schools
Greeley/Evans School District
Poudre School District
University of Colorado Health - North (Formerly -Poudre Valley Health System - PVHS)
Rocky Mountain National Park
Thompson School District
University of Colorado - Boulder
University of Colorado - Colorado Springs
University of Colorado - Denver
University of Colorado Health Sciences Center
University of Northern Colorado
Other (In the box below, list your study location if not checked above. You may also list details of your
already-checked location (e.g., specific school within a school district).
       
---------------------------------------------------------------------------------------------
* * * General Checklist * * *
 
General Checklist
         Select All That Apply :
X
Proposed Start Date (cannot be before IRB approval):
On receipt of IRB Approval
X
Sponsored Project (Check if you will be funded OR if you have or plan to submit a grant application in
association with this protocol)
NSF Sponsored (Please upload mandatory Data Management Plan in the Attachment section)


Page 8 of 44
 
8
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
X
FDA or EPA-regulated research.  Please contact the CSU Quality Assurance Manager, Cat Bens, at 970-
491-5445 to determine if your study is under Good Laboratory, Good Clinical, or Good Manufacturing
Practices (GLP, GCP, GMP).
 Training Grant
X
Clinical Trial.  To register your trial on Clinicaltrials.gov, please contact Cat Bens, CSU Quality Assurance
Manager and Clinical Trails Administrator at:  970-491-5445.
Project is associated with the Colorado School of Public Health - CSPH(faculty and/or student)
Cooperating/Collaborating Institution(s) Institution
where recruitment will occur OR Institution where
Collaborating PI will conduct associated research.
Interview
X
Questionnaire/Survey
X
 Subjects will be compensated for participation
Thesis or Dissertation Project
X
ÃÂ Radioisotopes/radiation-producing machines, even if standard of care.  Please contact Jim Abraham,
Radiation Safety Officer for questions related to use of all radiation-producing machine:  970-491-3736;
james.abraham@colostate.edu.  Upload your radiation-use approval  (if available) or your Radiation Safety
Training certificate in the attachment section.
X
Human blood, cells, tissues, or body fluids. You will need to obtain IBC approval if you check this box. For
information regarding IBC approval, contact Christine Johnson, IBC Coordinator:
christine.johnson@colostate.edu
 Tissues to be stored for future research projects
 Tissues to be sent out of this institution as part of a research agreement
Human Embryos. You will need to obtain IBC approval if you check this box. For information regarding IBC
approval, contact Christine Johnson, IBC Coordinator:  christine.johnson@colostate.edu
Human Embryonic Cells? Provide NIH Code Number(s)
or state that no federal funding will be used to support
this research. You may need to obtain IBC approval if
you check this box. For information regarding IBC
approval, contact Christine Johnson, IBC Coordinator:
christine.johnson@colostate.edu
 Use of Patient-related equipment? If Yes, specify what equipment is being used.
Medical equipment used for human patients/subjects also used on animals. For questions regarding animal
use approval, contact Elaine Kim, IACUC Senior Coordinator:  491-0236
Protocol involves studying potentially addicting drugs. For questions regarding approval for possession of
controlled substances, contact Chris Giglio, DRC Coordinator:  491-4830; Chris.Giglio@colostate.edu.
Investigational drugs, reagents, or chemicals (IND)


Page 9 of 44
 
9
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
X
 Commercially available drugs, reagents, or other chemicals administered to subjects (even if they are not
being studied)
Investigational Device (IDE)
Cancer Subjects (e.g., clinical trials, behavior/prevention) or Cancer Tissues (e.g., blood, cells, body fluids).
You may need to obtain IBC approval if you check this box. For information regarding IBC approval, contact
Christine Johnson, IBC Coordinator:  christine.johnson@colostate.edu
Other (clarify in text box to the right)
---------------------------------------------------------------------------------------------
* * * Funding * * *
 
Please complete this section if:  1. This protocol will be funded, 2. You have submitted or will submit a grant
application associated with this protocol.  Please be sure to input your PASS/SP1 number to assist Sponsored
Programs in setting up an account for your funds.
If this protocol is funded by the NIH or NSF, or will lead to the regulatory involvement of the FDA or EPA, please
be certain you are cognizant of any specific regulatory requirements for data acquisition, storage, retention and
sharing, as well as research expenditure allowability, with regard to this IRB protocol.
 
Funding Checklist
NONE
  
  
NOTE: Applicable Federal Grant Application, including competing renewals, must be attached in the
Attachment Section (#16). Applicable investigator's brochure and sponsor's protocol must also be
attached in section #16 for all industry-sponsored clinical trials.
 
Funding - Grants/Contracts
Funding Administered By
UNIVERSITY
CSU PASS #
120081
Sponsor's ID # (If known)
Funded By
Other
 
AstraZeneca
Principal Investigator
Bell
Grant/Contract Title if different from Protocol Title
For Federal projects, are contents of this protocol the
same as described in Federal proposal application?


Page 10 of 44
 
10
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
N
Is this an Umbrella protocol?
N
Is this protocol under an Umbrella protocol?
Funding - Fellowships
Funding - Other
 
Gift Funding
Dept. Funding
Other Funding
---------------------------------------------------------------------------------------------
* * * Expedited Paragraphs * * *
 
PLEASE READ:  This online application is for projects that will be reviewed by the IRB via the expedite or full-
board review process.  The criteria for expedited review are listed below. Review and check what expedite
criteria is/are appropriate for your project. NOTE:  If your research involves or may involve greater than minimal
risk, an element of deception, or is FDA-regulated research, do NOT check any of the expedited criteria listed
below.  Your protocol will then be reviewed by the full-board at their next regularly scheduled meeting.  If your
project meets the exempt criteria, please submit your exempt application via email to:
RICRO_IRB@mail.colostate.edu.  Information regarding exempt applications can be found here:
http://ricro.colostate.edu/IRB/ExemptReview.html
 
  Expedite Criteria:
 
1.
Clinical studies of drugs and medical devices only when condition (a) or (b) is met.
 
a) 
Research on drugs for which an investigational new drug application (21 CFR Part 31,32) is
not required. (Note: Research on marketed drugs that significantly increases the risks or
decreases the acceptability of the risks associated with the use of the product is not eligible
for expedited review.)
 


Page 11 of 44
 
11
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
b) 
Research on medical devices for which                                                                                       
                             
 
      i) 
An investigational device exemption application (21 CFR Part 812) is not required; or
      ii) 
The medical device is cleared/approved for marketing and the medical device is being used in
accordance with its cleared/approved labeling.
 
2.
Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
 
a) 
From healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, the
amounts drawn may not exceed 550 ml in an 8- week period and collection may not occur
more frequently than 2 times per week; or
 
b) 
From other adults and children, considering the age, weight, and health of the subjects, the
collection procedure, the amount of blood to be collected, and the frequency with which it will
be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3
ml per kg in an 8-week period and collection may not occur more frequently than 2 times per
week.
 
3.
Prospective collection of biological specimens for research purposes by non-invasive means.
 
4.
Collection of data through non-invasive procedures (not involving general anesthesia or sedation)
routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where
medical devices are employed, they must be cleared/approved for marketing. (Studies intended to
evaluate the safety and effectiveness of the medical device are not generally eligible for expedited
review, including studies of cleared medical devices for new indications.)
 
Examples:
a) 
Physical sensors that are applied either to the surface of the body or at a distance and do not
involve input of significant amounts of energy into the subject or an invasion of the subject's
privacy;
b) 
Weighing or testing sensory acuity;                                                                                              
           
c) 
Magnetic resonance imaging;                                                                                                      
     
d) 
Electrocardiography, electroencephalography, thermography, detection of naturally occurring
radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow,
and echocardiography;
e) 
Moderate exercise, muscular strength testing, body composition assessment, and flexibility
testing where appropriate given the age, weight, and health of the individual.


Page 12 of 44
 
12
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
 
5.
Research involving materials (data, documents, records, or specimens) that have been collected, or
will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). (NOTE:
Some research in this paragraph may be exempt from the HHS regulations for the protection of
human subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)
 
6.
Collection of data from voice, video, digital, or image recordings made for research purposes.
 
7.
Research on individual or group characteristics or behavior(including, but not limited to, research on
perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and
social behavior) or research employing survey, interview, oral history, focus group, program
evaluation, human factors evaluation, or quality assurance methodologies. (NOTE: Some research in
this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR
46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.)
 
 
---------------------------------------------------------------------------------------------
* * * Purpose,Study Procedures,Background * * *
 
Original Protocol Number (e.g., 07-226H)
Cloned and
subsequently
modified from 14-
5531H
   
Title (Please indicate if the protocol title is different from the proposal title)
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That Are Independent
Of Weight Loss In Overweight/Obese Adults
 
      Complete Sections 1 - 16. Specify N/A as appropriate. Do not leave any required sections blank.
1. Purpose of the study
a)
Provide a brief lay summary of the project in <200 words.  The lay summary should be readily
understandable to the general public, and is, for example, what would be released to a newspaper if
requested.
THIS PROTOCOL IS AN AMENDED/SIMPLIFIED VERSION OF IRB PROTOCOL 14-5531H.
Dapagliflozin is a medicine to treat diabetes.  Its mechanism of action is via sodium-glucose co-transporter
2 (SGLT2) inhibition.  In adults with diabetes, use of sodium-glucose co-transporter 2 inhibitors is
associated with moderate weight (fat) loss, in addition to other health benefits, including decreased blood
pressure, decreased inflammation, and decreased oxidative stress. It is unclear as to whether these health


Page 13 of 44
 
13
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
benefits are due to SGLT2 inhibition per se, or as a secondary effect of weight loss.  We wish to compare
the health benefits of dietary counseling for weight loss with and without concomitant use of an SGLT2
inhibitor.
 
b)
What does the Investigator(s) hope to learn from the study?
We wish to learn if:
1.  Dapagliflozin (SGLT2 inhibition) provides additional health benefits to dietary counseling for weight
loss?
and if,
2. Weight loss associated with dietary counseling and the use of  Dapagliflozin (SGLT2 inhibition) is
characterized by normal circulating satiety signals rather than the usual diet-induced changes in circulating
peptides that increase hunger and reduce satiety.
 
c)
Proposed Start Date (may not precede IRB approval date):
On receipt of IRB approval.
 
2. 
Study Procedures (If this is a student project, the methods section of the thesis or dissertation proposal
must be attached in section #16 - Attachment section.)
 
a)
In lay language, describe all the procedures, from screening through end-of-study, that the human subject
must undergo in the research project, including study visits, drug treatments, randomization and the
procedures that are part of standard of care.  Please note: Do NOT respond "See Attachment Section." If
you would like to add tables, charts, etc., attach those files in the Attachment section (#16).
OVERVIEW
This is a randomized, prospective, placebo-controlled, double blind, repeated measures study.  60
overweight/obese adults (body mass index > 27.5 kg/m^2) will be recruited for participation and randomly
assigned to one of two 12 week treatments: (1) daily oral administration of Dapagliflozin with dietary
counseling to promote weight loss; or, (2) daily oral administration of a placebo with dietary counseling to
promote weight loss.
Study participants will report to the research facilities on the Colorado State University main campus on 29
separate occasions:
Visit 1: study participants will undergo screening: medical history, 12-lead electrocardiogram and blood
pressure assessment at rest and during incremental exercise to volitional exhaustion, blood sampling, and
measurement of body composition.
Visit 2: an oral glucose tolerance test will be performed and resting metabolic rate and blood pressure will


Page 14 of 44
 
14
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
be measured.
Visit 3: appetite and hunger will be assessed and participants will be given a 3-dietary record form to
complete.
Visits 4-27: 12 weeks of nutrition counseling/weighing (upto 2 visits per week for 12 weeks).  Concurrent
with these visits, research participants will ingest, on a daily basis, either Dapagliflozin or placebo.
Visit 28: an oral glucose tolerance test will be performed and resting metabolic rate and blood pressure will
be measured.
Visit 29: appetite and hunger will be assessed; body composition will be measured, and participants will be
given a 3-day dietary record form to complete.
DETAILED DESCRIPTION OF STUDY PROCEDURES
Visit 1: study participants will provide informed consent and undergo screening: medical history, 12-lead
electrocardiogram and blood pressure assessment at rest and during incremental exercise to volitional
exhaustion, blood sampling, and measurement of body composition.
These screening procedures are standard for our lab.  Each of the procedures is currently active in other
IRB-approved protocols (e.g. 12-3767H, 08-611H, 14-4756H).
Health History - Potential participants will complete a standardized health history questionnaire that will
address past and present medication use, allergies, past and present medical conditions and physical
injuries, and habitual use of alcohol and tobacco.
Body composition - Percent body-fat, fat-free mass, total and regional adipose tissue mass, and total bone
mineral density will be determined using a whole-body dual energy x-ray absorptiometry scan (DEXA,
Model DPX-IQ Lunar Corp., Madison, WI).
Maximal graded exercise stress testing - A 12-lead ECG, arterial blood pressure (brachial
sphygmomanometer) will be obtained during quiet resting conditions in the supine and upright sitting
positions, and during incremental stationary cycle ergometer or treadmill exercise until volitional fatigue.
During exercise, oxygen consumption, carbon dioxide production and ventilation may be determined by
indirect calorimetry.  All data from these tests will be will be reviewed by a cardiologist.  Only those
subjects demonstrating no signs or symptoms of disease will be invited to participate in the study.
Blood sampling – Blood (~ 20 ml) will be sampled from an antecubital or hand vein for subsequent analysis
of circulating factors pertinent to inclusion/exclusion criteria, including glucose, aspartate
aminotransferase, alanine aminotransferase,and  total bilirubin.  These blood analyses will be performed in
on-site (Piccolo Xpress, Abaxis, Union City, CA). Testing for Hepatitis B/C will be performed at a local,
external clinical lab (e.g. University of Colorado-Health North).  Per the Medical Monitor’s discretion follow
up blood draws maybe requested.
Visit 2: Resting Metabolic Rate (ventilated hood technique,indirect calorimetry) for 45 minutes and blood
pressure will be measured. An oral glucose tolerance test will be performed.


Page 15 of 44
 
15
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
These procedures are standard for our lab.  Each of the procedures is currently active in other IRB-
approved protocols (e.g. 14-5201H).
Blood pressure will be determined three times using the left arm via standard procedures. Each
assessment will be separated by 3 minutes. The mean of the three measurements will be recorded.
Participants will report to the laboratory early in the morning, following a 12-hour fast and 24-hour
abstention from exercise. An intravenous catheter will be inserted into an antecubital or hand vein and kept
patent with a saline drip.  Following baseline blood sampling for fasting glucose and insulin, participants
will ingest 75 g of dextrose dissolved in 250 ml of water over 10-minutes.  Venous blood (~ 9 ml) will be
sampled at time 0 (baseline) and 5, 10, 15, 20, 30, 45, 60, 75, 90 105 and 120 minutes for determination of
concentration of blood glucose (2300 STAT Plus Glucose Lactate Analyzer, YSI Inc., Yellow Springs,
Ohio), and insulin (commercially available assay).
Prior to the start of the oral glucose tolerance test, venous blood (~ 20 ml) will be sampled, and
plasma/serum and red cells isolated and stored at -70°C for subsequent analysis of circulating markers of
inflammation (High sensitive C-Reactive Protein, Tumor Necrosis Factor Alpha, and Interleukin 6) and
oxidative stress (oxidized low density lipoprotein concentration, and thiobarbituric acid reactive
substances).
Visit 3: Appetite and hunger will be assessed.
These procedures are standard for our lab.  Each of the procedures is currently active in other IRB-
approved protocols (e.g. 12-3567H).
On a day different to the oral glucose tolerance day, participants will report to the laboratory early in the
morning, following a 12-hour fast and 24-hour abstention from exercise. An intravenous catheter will be
inserted into an antecubital or hand vein and kept patent with a saline drip. Participants will be provided
with a standardized “priming meal” comprising a commercially available, mixed-nutrient liquid meal, dosed
to 1 kcal per kg body mass (Ensure, Ross Laboratories, Abbott Park, IL; 64% CHO, 22% fat, 14% protein).
One hour following consumption of this priming meal, participants will be presented with a pre-weighed
buffet of food from which they will have opportunity to eat ad libitum quantities over a 30 minute period.
The remaining uneaten food will be reweighed and participants’ energy and macronutrient intakes will later
be determined using the Food Intake Analysis System software (U Texas Health Sciences Center,
Houston). Prior to the standardized primer meal, and to the buffet, and then every 60 minutes over 3 hours
following the buffet, participants will be asked to rate their perceptions of hunger and satiety using a visual
analog scale. At these same time points, venous blood (~ 20 ml) will be sampled, and plasma/serum
isolated and stored at -70°C for subsequent determination of concentrations of hunger and satiety
hormones (e.g. ghrelin, peptide YY, leptin, and insulin). At the conclusion of these tests, the study
participant will give a form in which to record the amounts of food and beverage (except water) they eat
and drink for three consecutive days, including 2 week days and 1 weekend day. Upon completion of the
food records, the form will be returned to the research team. This information will be used to establish
baseline dietary intake and will be useful information for the nutrition counselors seeking to help the
participants lose weight.


Page 16 of 44
 
16
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Visits 4-27: During the first 6 weeks participants will meet with a study counselor 2 times per week for
dietary counseling and measurement of body weight.  During the second 6-week period they will meet 1-2
times per week for dietary counseling and body weight measurement, depending on whether or not they
are meeting weight loss goals. If they are losing weight as prescribed, they will meet only once per week,
but if they are not meeting weight loss goals they will meet 2 times per week.  Participants will need to fast
for 10 hours prior to the weigh-in. On 2 random counseling occasions between weeks 4 and 10, they will
be asked to recall what they ate during the previous 24 hours.  If participants fail to achieve their target
body weight (within 1 kg or 2.2 lbs) on three consecutive weighing sessions, they will be provided with
additional counseling and instructions to aid in achieving your target body weight.
During the first two weeks of the 12 week intervention, participants will ingest one pill daily (5 mg DAPA)
and for the remaining 10 weeks participants will ingest 2 pills daily (a total of 10 mg DAPA). On 3 random
weigh-in occasions between weeks 4 and 10, participants will be asked to recall what they ate during the
previous 24 hours.
Visit 28:  Resting Metabolic Rate Test, Oral Glucose Tolerance Test, and Blood Pressure will be measured
(e.g. the final week of daily ingestion of Dapagliflozin). See description of Visit 2.
Visit 29: in the HPCRL appetite and hunger will be assessed this visit will occur in week 12  (e.g. during the
final week of daily ingestion of Dapagliflozin).  Body composition will be measured at this visit or early the
following week (e.g. week 13). The study participants will also be given the 3-day food intake record form
to be completed and returned to the research team.
 
b)
Explain why human subjects must be used for this project.
Dapagliflozin is approved for human use.  Due to potential species differences it would not be appropriate
to perform these studies on experimental animals.
 
c)
Alternative Procedures. If the proposed study is a clinical trial of a drug, vaccine, device or treatment,
describe alternative procedures, if any, that might be advantageous to the subject. Describe the important
potential risks and benefits associated with the alternative procedure(s) or course(s) of treatment. Any
standard treatment that is being withheld must be disclosed. This information must be included in the
consent form.
There are no appropriate alternative procedures.
 
d)
If the proposed study is a clinical trial of a drug, vaccine, device or treatment, will it be possible to continue
the more (most) appropriate therapy for the subject(s) after the conclusion of the study?
Not applicable.
 
e)
Study Endpoint. If the proposed study is a clinical trial of a drug, vaccine, device or treatment, what are the
guidelines or end points by which you can evaluate the alternative treatments during the study? If one
treatment proves to be clearly more effective than another (or others) will the study be terminated before
the projected total subject population has been enrolled? When will the study end if no important


Page 17 of 44
 
17
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
differences are detected?
Not applicable.
 
f)
State if deception will be used. If so, provide a rationale and describe debriefing procedures. Submit a
debriefing script in the Attachment Section (#16).
There will be no deception.  Subjects may receive Dapagliflozin or a placebo; they will not know which
treatment (Dapagliflozin or placebo) they receive until study completion.
 
3. Background
a)
Describe past experimental and/or clinical findings leading to the formulation of the study, if applicable.
Aside from the metabolic benefits pertaining to glucose control, inhibition of sodium-glucose co-transporter
2 (SGLT2) in patients is associated with moderate weight loss (Tahrani et al., 2011; Chen & Leung, 2013),
with some studies reporting up to 4.5 kg decreases in body mass over 12 weeks (Wilding et al., 2009).
Animal data are consistent with these observations (Devenny et al., 2012; Liang et al., 2012). SGLT2
inhibition is also associated with other health benefits, including decreased blood pressure (Ferrannini et
al., 2010; Dobbins et al., 2012), decreased inflammation (Chen et al., 2012; Tahara et al., 2013, 2014),
and decreased oxidative stress (Tahara et al., 2013, 2014)—all health benefits with very important
implications for improved physiological function and decreased disease-risk. At present, it is unclear as to
whether these health benefits are due to SGLT2 inhibition per se, or as a secondary effect of weight loss.
Noteworthy, the weight loss observed in patients associated with SGLT2 inhibition is not mediated by
intentional dietary restriction/intervention.  It is more likely to be mediated by the caloric loss associated
with the decreased renal tubular reabsorption of glucose, leading to urinary glucose excretions ranging
between 45 and 80 g/day (180-320 kcal/d), depending on the drug dose (Idris & Donnelly, 2009). This
caloric deficit is not trivial. Typically, caloric deficits of this magnitude require either increased physical
activity and/or dietary restriction.
In our original study (Protocol 14-5531H) we learned that when adults with normal, healthy glucose control
use SGLT2 inhibitors, the weight loss is negligible.  Nevertheless, even in healthy adults, SGLT2 inhibition
leads to glucose spillage into urine that may elicit other, non-wight loss mediated health benefits. Therefore
in the current project we will study the use of SGLT2 inhibitors combined with dietary counseling for weight
loss.
The limitations of the use of dietary restriction for weight loss and, perhaps more importantly, sustained
lower weight maintenance, are well described (MacLean et al., 2006; Strohacker et al., 2014). In response
to diet-induced weight loss several biological factors, including increased appetite owing to elevation of the
orexigenic hormone, ghrelin, and decreased anorexigenic hormones like peptide YY (PYY), promote
increased dietary intake and subsequently weight re-gain. However, it is biologically plausible that the
weight loss accompanying SGLT2 inhibition may not be accompanied by increased appetite as the unique
mechanism of action allows the patient to consume/ingest calories (carbohydrates), but limits the ability for
internal storage. That is, during eating, nutrient sensors within the gut release satiety factors to inhibit
further dietary intake (Schaeffer et al., 2014; Strohacker et al., 2014). Ingesting calories as carbohydrates
while using SGLT2 inhibitors may allow for normal satiety signaling while limiting caloric storage, thus
thwarting biological impediments to long-term weight loss.


Page 18 of 44
 
18
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
thwarting biological impediments to long-term weight loss.
Accordingly, in light of the rationale provided, we wish to determine if: 1.  Dapagliflozin (SGLT2 inhibition)
provides additional health benefits to dietary counseling for weight loss?  2. Weight loss associated with
dietary counseling and the use of  Dapagliflozin (SGLT2 inhibition) is characterized by normal circulating
satiety signals rather than the usual diet-induced changes in circulating peptides that increase hunger and
reduce satiety.
REFERENCES (Some of which have been provided as attachments)
Chen L, Klein T & Leung PS. (2012). Effects of combining linagliptin treatment with BI-38335, a novel
SGLT2 inhibitor, on pancreatic islet function and inflammation in db/db mice. Curr Mol Med 12, 995-1004.
Chen LH & Leung PS. (2013). Inhibition of the sodium glucose co-transporter-2: its beneficial action and
potential combination therapy for type 2 diabetes mellitus. Diabetes Obes Metab 15, 392-402.
Devenny JJ, Godonis HE, Harvey SJ, Rooney S, Cullen MJ & Pelleymounter MA. (2012). Weight loss
induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced
obese (DIO) rats. Obesity (Silver Spring) 20, 1645-1652.
Dobbins RL, O'Connor-Semmes R, Kapur A, Kapitza C, Golor G, Mikoshiba I, Tao W & Hussey EK.
(2012). Remogliflozin etabonate, a selective inhibitor of the sodium-dependent transporter 2 reduces
serum glucose in type 2 diabetes mellitus patients. Diabetes Obes Metab 14, 15-22.
Ferrannini E, Ramos SJ, Salsali A, Tang W & List JF. (2010). Dapagliflozin monotherapy in type 2 diabetic
patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-
controlled, phase 3 trial. Diabetes Care 33, 2217-2224.
Idris I & Donnelly R. (2009). Sodium-glucose co-transporter-2 inhibitors: an emerging new class of oral
antidiabetic drug. Diabetes Obes Metab 11, 79-88.
Liang Y, Arakawa K, Ueta K, Matsushita Y, Kuriyama C, Martin T, Du F, Liu Y, Xu J, Conway B, Conway J,
Polidori D, Ways K & Demarest K. (2012). Effect of canagliflozin on renal threshold for glucose, glycemia,
and body weight in normal and diabetic animal models. PLoS One 7, e30555.
MacLean PS, Higgins JA, Jackman MR, Johnson GC, Fleming-Elder BK, Wyatt HR, Melanson EL & Hill
JO. (2006). Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient
regain in obesity-prone rats. Am J Physiol Regul Integr Comp Physiol 290, R1577-1588.
Schaeffer M, Hodson DJ & Mollard P. (2014). The blood-brain barrier as a regulator of the gut-brain axis.
Front Horm Res 42, 29-49.
Strohacker K, McCaffery JM, MacLean PS & Wing RR. (2014). Adaptations of leptin, ghrelin or insulin
during weight loss as predictors of weight regain: a review of current literature. Int J Obes (Lond) 38, 388-
396.


Page 19 of 44
 
19
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q,
Tomiyama H, Kobayashi Y, Noda A, Sasamata M & Shibasaki M. (2013). Effects of SGLT2 selective
inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation,
and obesity in type 2 diabetic mice. Eur J Pharmacol 715, 246-255.
Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q,
Tomiyama H, Kobayashi Y, Noda A, Sasamata M & Shibasaki M. (2014). Effects of sodium-glucose
cotransporter 2 selective inhibitor ipragliflozin on hyperglycaemia, oxidative stress, inflammation and liver
injury in streptozotocin-induced type 1 diabetic rats. J Pharm Pharmacol.
Tahrani AA, Bailey CJ, Del Prato S & Barnett AH. (2011). Management of type 2 diabetes: new and future
developments in treatment. Lancet 378, 182-197.
Wilding JP, Norwood P, T'Joen C, Bastien A, List JF & Fiedorek FT. (2009). A study of dapagliflozin in
patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel
insulin-independent treatment. Diabetes Care 32, 1656-1662.
 
b)
Describe any animal experimentation and findings leading to the formulation of the study, if applicable.
See previous section (3a).
---------------------------------------------------------------------------------------------
* * * Radioisotopes or Radiation Machines * * *
 
 
You selected NO for Radioisotopes in the General Checklist. If you would like to add Radioisotopes, change the
selection to YES in general Checklist.
 
4. 
Radioisotopes or Radiation Machines Please note: For projects requiring radiation procedures, please
contact the CSU Radiation Control Office (RCO). For more information see:
http://www.ehs.colostate.edu/WRad/Home.aspx :
 
 
a) 
If applicable, summarize in lay language the radiographic diagnostic and therapeutic procedures
associated with this protocol.
Body composition will be measured by dual energy x-ray absorptiometry (DEXA) at pre and post
treament
  b) 
Are the radiation procedures being performed a normal part of the clinical management for the medical
condition that is under study (Standard of Care) or are the procedures being performed because the
research subject is participating in this project (extra CT scans, more fluoroscopy time, additional Nuclear


Page 20 of 44
 
20
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Medicine Studies, etc.,) (Not Standard of Care)? If some procedures are Standard of Care and some are
Not Standard of Care, check both boxes.
 
  
NOT STANDARD OF CARE
X
STANDARD OF CARE
  
If it is not standard of care, complete the rest of
this section. Provide the CSU RCO approval
information
If it is only standard of care, skip the rest of this
section.
 
 
CSU Radiation Control Office approved protocol number:
 
 
CSU Radiation Control Office protocol approval date:
 
For more information, see the RCO website at:http://www.ehs.colostate.edu/Wrad/home.aspx or Contact:
James Abraham, Radiation Safety Officer, at 970-491-3736.
---------------------------------------------------------------------------------------------
* * * Medical Equipment for Human Subjects and Laboratory Animals; Investigatiional Devices * * *
 
 
5. Medical Equipment for Human Subjects
 
  
If medical equipment is being used for human subjects/patients, describe this equipment and indicate if the
use is normal practice for the population under study. You may have already described this equipment in
the Study Procedures section. If you have already listed this information in the Study Procedures Section,
please do not duplicate this information here. In the space below, input N/A if not applicable, indicate if this
is already listed in the Study Procedures Section, or describe the equipment.
N/A
 
 
6. Investigational Devices
         Please list in the space below all Investigational Devices to be used on Subjects.
Investigational Devices
---------------------------------------------------------------------------------------------


Page 21 of 44
 
21
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
* * * Drugs, Reagents, or Chemicals * * *
 
 
7. Drugs, Reagents, or Chemicals
 a)
Please list in the space below all investigational drugs, reagents or chemicals to be administered to
subjects during this study.
 
 b)
Please list in the space below all commercial drugs, reagents or chemicals to be administered to subjects
during this study.
 
Drug Name
Dapagliflozin
Source (e.g., Pharmacy, Sponsor, etc.,)
AstraZeneca Pharmaceuticals LP
If not premixed, where will the material be mixed and
by whom
Pre-mixed by Bristol-Myers Squibb Company
Manufacturer
Bristol-Myers Squibb Company
IND # (if available)
n/a
Dosage
5 mg/day of Dapagliflozin for the first 14-days, and
then a dose increase to 10 mg/day of Dapagliflozin
for remaining 10 weeks.
Administration Route
Oral
Y
 Are these new or different uses of these
commercially available drugs, reagents, or
chemicals?
N
IND Regulations
 
Please read the IND Statements
---------------------------------------------------------------------------------------------
* * * Subject Population (a-g) * * *
 
 


Page 22 of 44
 
22
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
8.  
Subject Population - In the space below, please detail the participants that you are requesting to recruit
(include requested participant number and description of each group requested).  (Input N/A if not
applicable)
a)
Requested Participant Description (Include number of participants that you plan to study and description of
each group requested, if applicable).
60 overweight/obese adult volunteers (men and women) will be studied.  However, the number enrolled
may be higher in the event of enrollment of replacement subjects for dropout(s) that discontinued for
reasons other than an adverse event due to study medication. In the event of a replacement subject being
enrolled, this subject will complete all visits. Therefore we would like to enroll 200 participants.
Participants previously enrolled in 14-5531H and withdrawn due to new information will be contacted per
for future enrollment in this study. Several procedures, such as screening and DEXA, OGTT, will not be
redone, but will be released for the purposes of this purpose. You can find the participant letter that went
out to those participants in the attachments section.
 
b)
What is the rationale for studying the requested group(s) of participants?
Adults who are overweight/obese are at the greatest risk of developing type 2 diabetes, thus
overweight/obese adults potentially have the most to gain should the outcome of the study prove
favorable.  Inclusion of adults already diagnosed with diabetes might complicate the interpretation of the
data; that is, as a consequence of the patho-physiology associated with diabetes, the response to our
feeding treatment with or without Dapagliflozin may differ in adults with diabetes compared with adults who
are diabetes free.
 
c)
If applicable, state the rationale for involvement of potentially vulnerable subjects to be entered into the
study, including minors, pregnant women, economically and educationally disadvantaged, or decisionally
impaired subjects. Specify the measures being taken to minimize the risks and the chance of harm to the
potentially vulnerable subjects.
Potentially vulnerable subjects will not be studied.
 
d)
If women, minorities, or minors are not included, a clear compelling rationale must be provided. Examples
for not including minors: disease does not occur in children; drug or device would interfere with normal
growth and development; etc.
Women and minorities will be invited to participate.  Minors will be excluded.  The prevalence of type 2
diabetes is greater in adults than minors.  Safety and effectiveness of Dapagliflozin in pediatric patients
under 18 years of age have not been established.
 
e)
State if any of the subjects are students, employees, or laboratory personnel. They should be presented
with the same written informed consent. If compensation is allowed, they should also receive it.
If any of the subjects are students, employees, or laboratory personnel they will be presented with the


Page 23 of 44
 
23
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
same written informed consent; compensation is allowed, they will also receive it.
 
f) 
Describe how potential subjects will be identified for recruitment (e.g., chart review, referral from individual's
treating physician, those individuals answering an ad). How will potential participants learn about the
research and how will they be recruited (e.g., flyer, email, web posting, telephone, etc.)? Attach recruitment
materials in the Attachment Section (#16). Important to remember: potential subjects may not be contacted
before IRB approval.
Please see examples of recruitment materials in the attachment section.
Potential subjects will be recruited via electronic advertisement (e.g. The Source) and email lists (e.g. CSU
genfac).  If necessary, potential subjects may also be recruited via newspaper advertisement (e.g. The
Coloradoan), clinical trials websites (e.g. clinicaltrials.gov), and/or flyers/posters placed in public places
(e.g. coffee shops) in and around the Fort Collins area. Public places includes using approved recruitment
texts in social media forums.
 
g) 
If applicable, provide rationale for the inclusion of healthy volunteers in this study. Specify any risks to
which these healthy volunteers may possibly be exposed. Specify the measures being taken to minimize
the risks and the chance of harm to these volunteers.
Adults who are overweight/obese but otherwise healthy will be invited to participate.  Inclusion of adults
already diagnosed with diabetes might complicate the interpretation of the data; that is, as a consequence
of the patho-physiology associated with diabetes, the response to feeding with or without Dapagliflozin
may differ in adults with diabetes compared with adults who are diabetes free.
It is not possible to identify all potential risks in research procedures, but the researcher(s) have taken
reasonable safeguards to minimize any known and potential (but unknown) risks.  The Human
Performance Clinical Research Laboratory has emergency supplies including a medicine trolley equipped
with heart machines and supplemental oxygen.  The research team has a great deal of experience with all
of the procedures.  Some of the procedures for which you are being asked to volunteer have a number of
associated risks:
Body Composition
The risks associated with the DEXA are very low.  The maximum radiation dose you will receive in this
study is less than 1/1000th of the federal and state occupational whole body dose limit allowed to radiation
workers (5,000 mrem).  Put another way, the maximum dose from any scan we utilize with this DEXA
ranges from 1.2 mrem (Whole body scan) to 12.2 mrem (for several of the regional scans, such as lumbar,
femur, and forearm scans).  The average annual background radiation you already receive is at least 620
mrem/year.  The more radiation you receive over the course of your life, the more the risk increases of
developing a fatal cancer or inducing changes in genes.  The radiation in this scan is not expected to
significantly increase these risks, but the exact increase in such risks is not known.  There are no
discomforts associated with this procedure. Women who are or could be pregnant should receive no
unnecessary radiation and should not participate in this study.
Women will complete a pregnancy test before participating in a DEXA scan.
Exercise Tests


Page 24 of 44
 
24
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
There is a very small chance of an irregular heartbeat during exercise (< 1% of all subjects).  Other rare
risks of a stress test are heart attack (< 5 in 10,000) and death (<2 in 10,000).  Wearing a mouthpiece and
nose-clip can sometimes cause dryness in the mouth and mild discomfort. Difficult exercise may make you
feel very tired, light headed and nauseous.  Exhausting exercise will, by definition, make you feel very
tired.  After any exercise your muscles might ache.
ACSM guidelines pertinent to the requirement of physician supervised exercise (stress) testing will be
followed.
Blood Collection
When the needle goes into a vein, it may hurt for a short period of time (a few seconds).  Also there may
be minor discomfort of having the needle/plastic tube taped to your arm.  In about 1 in 10 cases, a small
amount of bleeding will occur under the skin that will cause a bruise.  The risk of forming a blood clot in the
vein is about 1 in 100, and the risk of significant blood loss is 1 in 1,000.  Additionally, there is a risk that
you may faint while having blood collected or having the catheter inserted in your vein.
Only trained research personnel will be permitted to perform phlebotomy.
---------------------------------------------------------------------------------------------
* * * Subject Population (h-m) * * *
 
 
8. Subject Population (Input N/A if not applicable)
h)
Inclusion and Exclusion Criteria (e.g., Participants must have 20/20 vision, Participants must be 30-45
years of age, etc.)
 
 
  
   
Identify inclusion criteria.
For inclusion in the study subjects should fulfill the following criteria:
1.Provision of informed consent prior to any study specific procedures.
2.Aged 18-65 years.
3.No known Type 2 Diabetes
4.Body mass index greater than or equal to 27.5 kg/m^2
5.Limited exercise participation (maximum of 3/week regularly scheduled activity sessions of <
30 minutes during the previous month).
6.Completion of a screening visit consisting of medical history, physical examination, and 12-
lead electrocardiogram and blood pressure assessment at rest and during incremental exercise
to volitional exhaustion (Note: Subjects with abnormal screening values may be eligible if the
results are not clinically significant, as judged by the investigator or medical monitor)
7.Agree to abide by the study schedule and dietary restrictions and to return for the required
assessments
8.Women of childbearing potential must have negative pregnancy test and be using acceptable
contraception


Page 25 of 44
 
25
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
 
 
  
   
Identify exclusion criteria.
Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
1.Evidence of clinically significant cardiovascular, respiratory, renal, hepatic, pulmonary,
gastrointestinal, haematological, neurological, psychiatric, or other disease that may interfere
with the objectives of the study or the safety of the subject, as judged by the investigator in
agreement with the sponsor or medical monitor, have been hospitalized in the past 2 years as a
result of these conditions, or are receiving pharmacological treatment for these conditions.
2.Use of prescription drugs (see exceptions listed below) or herbal preparations in the 2 weeks
before study commencement. Prior use of medication or herbal preparations in the 4 weeks
before study commencement that are intended for weight-loss and/or sold/marketed as weight-
loss products or may alter metabolism.
Permitted Prescription Drugs:
•Birth Control
•Less than a 10 day short course of antibiotics. Note: Rifampicin is not permitted.Antibiotics
prescribed for any serious condition will be reviewed on case by case basis no matter the
course prescribed.
•Other medicines, such as those for GERD, depression, and OTC analgesics and allergy
medications, may be allowed, but will be approved on a case-by-case basis.
3.Is currently enrolled in another clinical study for another investigational drug or has taken any
other investigational drug within 30 days before the screening visit.
4.Habitual and/or recent use (within 2 years) of tobacco.
5.Being considered unsuitable for participation in this trial for any reason, as judged by the
investigator or medical monitor.
6.History of serious hypersensitivity reaction to Dapagliflozin.
7.Severe renal impairment, end-stage renal disease, or dialysis.
8.Pregnant or breastfeeding individual.
9.Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate
aminotransferase (AST) >3x upper limit of normal and/or alanine aminotransferase (ALT) >3x
upper limit of normal.
10.Total bilirubin >2.0 mg/dL (34.2 umol/L).
11.Positive serologic evidence of current infectious liver disease including Hepatitis B viral
antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody.
12.Estimated Glomerular Filtration Rate <60 mL/min/1.73 m^2 (calculated by Cockcroft-Gault
formula).
13.History of bladder cancer.
14.Recent cardiovascular events in a patient, including any of the following: acute coronary
syndrome within 2 months prior to enrolment; hospitalization for unstable angina or acute
myocardial infarction within 2 months prior to enrolment; acute stroke or trans-ischemic attack
within two months prior to enrolment; less than two months post coronary artery
revascularization; congestive heart failure defined as New York Heart Association class IV,
unstable or acute congestive heart failure. Note: eligible patients with congestive heart failure,
especially those who are on diuretic therapy, should have careful monitoring of their volume
status throughout the study.
15.Blood pressure at enrolment: Systolic blood pressure ≥160 mmHg and/or diastolic blood
pressure ≥100 mmHg.


Page 26 of 44
 
26
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
16.Blood pressure at randomization: Systolic blood pressure ≥165 mmHg and/or diastolic blood
pressure ≥100 mmHg
17.Individuals who, in the judgment of the medical monitor, may be at risk for dehydration.
18.  Individuals with a history of fragility fracture, or bone mineral density values reflective of
risk for fracture (DEXA Z-score <or= to -2 in pre-menopausal women, and men <50, and T-
score <or= to -1) will not be permitted to participate.
 
i)
Describe your screening procedures. Attach your screening document(s) (e.g., health history
questionnaire) in the Attachment Section (#16).
Please see attached screening document.  Subjects will be provided with the option of receiving an
electronic version of the screening document in advance of visit 1.
 
j)
Describe how you will be cognizant of other protocols in which subjects might be participating. Please
explain if subjects will be participating in more than one study.
Subjects will asked if they are participating in another study or if they intend to enroll in another study.
Subjects will be permitted to participate in other studies when participation does not interfere with the
current study - that is, no possible interaction with Dapagliflozin or feeding, no increase risk to subject
safety, etc.
 
k)
Compensation. Explain the amount and schedule of compensation, if any, that will be paid for participation
in the study. Compensation includes food, gift cards, money, tokens, etc. Include provisions for prorating
payment, if applicable.  Compensation should be prorated if several activities are involved for different time
periods (e.g., $10 for session #1, and $10 for session #2).
Participants are provided with the following information in the consent form: "If you complete all of the
visits, and all of the procedures as described for the entire study, you will receive up to $400 in total
compensation. $300 will be paid in installments and prorated as follows: you will not receive compensation
for visit 1 (the screening visit). You will receive $60 following completion of baseline testing (visits 2, and
3).  After successfully completing 8 weeks of the intervention you will receive $60; after completing 12
weeks you will receive $60. You will receive $60 for completion of visit 28, and $60 for completion of visit
29. If you are at least 95% compliant in terms of both visits and pill ingestion, you will receive an additional
$100.
Should your participation in the study end early, you will still receive feedback pertaining to your health and
fitness."
 
l)
Costs. Please explain any costs that will be charged to the subject.
Subjects are provided with the following information: "Other than transport to and from the lab, your
participation should incur no costs.
 
m)
Estimate the probable duration of the entire study. This estimate should include the total time each subject


Page 27 of 44
 
27
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
is to be involved and the duration the data about the subject is to be collected (e.g., This is a 2-year study.
Participants will be interviewed 3 times per year; each interview will last approximately 2 hours.  Total
approximate time commitment for participants is 12 hours).  These times should be consistent with the time
commitment listed on the consent document.
The study will take place over approximately 3 years.  Subjects will be involved only for approximately 4
months and will be asked to visit the Human Performance Clinical Research Laboratory and/or Nutrition
and Metabolic Fitness Laboratory in the Gifford Building at CSU on 29 different occasions.  Visits will last
between 30 minutes and 5 hours.
---------------------------------------------------------------------------------------------
* * * Risks * * *
 
 
9. Risks (Input N/A if not applicable)
     
US Department of Health & Human Services (HHS) Regulations define a subject at risk as follows: "...any
individual who may be exposed to the possibility of injury, including physical, psychological, or social injury,
as a consequence of participation as a subject in any research, development, or related activity which
departs from the application of those accepted methods necessary to meet his needs, or which increases
the ordinary risks of daily life, including the recognized risks inherent in a chosen occupation or field of
service."
 
 a) 
PI's evaluation of the overall level of Risk. (Please check one: minimal or > minimal.)
Minimal (everyday living)
Y
> Minimal (greater than everyday living)
 
 b)   
For the following categories include a scientific estimate of the frequency, severity, and reversibility of
potential risks. Wherever possible, include statistical incidence of complications and the mortality rate of
proposed procedures. Where there has been insufficient time to accumulate significant data ON risk, a
statement to this effect should be included. (In describing these risks in the consent form to the subject, it is
helpful to use comparisons which are meaningful to persons unfamiliar with medical terminology.) Address
any risks related to:
 
 
   
   
1.   
Use of investigational devices. Please include the clinical adverse events (AEs) associated with
each of the devices with an indication of frequency, severity and reversibility. This information
can often be found in the Investigator(s) brochure.
N/A


Page 28 of 44
 
28
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
 
 
   
   
2   
Use of investigational drugs. Please include the clinical AEs associated with each of the drugs
with an indication of frequency, severity and reversibility. This information can often be found in
the Investigator(s) brochure.
N/A
 
 
   
   
3   
Use of commercially available drugs, reagents or chemicals. Please include the clinical AEs
associated with each of the drugs with an indication of frequency, severity and reversibility. This
information can often be found in the package insert provided by the manufacturer.
Please see the package insert provided by the manufacturer for further information.
Adverse reactions in placebo-controlled studies reported in more than 2% but less than 8.5 %
of patients treated with Dapagliflozin include:
•Female genital mycotic infections, such as (listed in order of frequency reported): vulvovaginal
mycotic infection, vaginal infection, vulvovaginal candidiasis, vulvovaginitis, genital infection,
genital candidiasis, fungal genital infection, vulvitis, genitourinary tract infection, vulval abscess,
and vaginitis bacterial.
•Nasopharyngitis (cold-like symptoms)
•Urinary tract infections, such as (listed in order of frequency reported): urinary tract infection,
cystitis, Escherichia urinary tract infection, genitourinary tract infection, pyelonephritis, trigonitis,
urethritis, kidney infection, and prostatitis.
•Back pain
•Increased urination
•Male genital mycotic infections, such as (listed in order of frequency reported): balanitis, fungal
genital infection, balanitis candida, genital candidiasis, genital infection male, penile infection,
balanoposthitis, balanoposthitis infective, genital infection, and posthitis.
•Influenza
•Nausea
•Dyslipidemia
•Constipation
•Discomfort with urination


Page 29 of 44
 
29
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
•Pain in extremity
In addition, use of Dapagliflozin is also associated with a risk of weight loss (up to 10 lbs over
12 weeks).
 
 
   
   
4   
When performing procedures, please include all investigational, non-investigational and non-
invasive procedures (e.g., surgery, blood draws, treadmill tests).
Subjects are provided with the following information pertaining to risks:
Body Composition
The risks associated with the DEXA are very low.  The maximum radiation dose you will receive
in this study is less than 1/1000th of the federal and state occupational whole body dose limit
allowed to radiation workers (5,000 mrem).  Put another way, the maximum dose from any scan
we utilize with this DEXA ranges from 1.2 mrem (Whole body scan) to 12.2 mrem (for several of
the regional scans, such as lumbar, femur, and forearm scans).  The average annual
background radiation you already receive is at least 620 mrem/year.  The more radiation you
receive over the course of your life, the more the risk increases of developing a fatal cancer or
inducing changes in genes.  The radiation in this scan is not expected to significantly increase
these risks, but the exact increase in such risks is not known.  There are no discomforts
associated with this procedure. Women who are or could be pregnant should receive no
unnecessary radiation and should not participate in this study.
Exercise Tests
There is a very small chance of an irregular heartbeat during exercise (< 1% of all subjects).
Other rare risks of a stress test are heart attack (< 5 in 10,000) and death (<2 in 10,000).
Wearing a mouthpiece and nose-clip can sometimes cause dryness in the mouth and mild
discomfort. Difficult exercise may make you feel very tired, light headed and nauseous.
Exhausting exercise will, by definition, make you feel very tired.  After any exercise your
muscles might ache.
Blood Collection
When the needle goes into a vein, it may hurt for a short period of time (a few seconds).  Also
there may be minor discomfort of having the needle/plastic tube taped to your arm.  In about 1
in 10 cases, a small amount of bleeding will occur under the skin that will cause a bruise.  The
risk of forming a blood clot in the vein is about 1 in 100, and the risk of significant blood loss is 1
in 1,000.  Additionally, there is a risk that you may faint while having blood collected or having
the catheter inserted in your vein.
Resting Metabolic Rate
The risks associated with this measurement are very low.  Some people might feel
claustrophobic (fear of small places) when the bubble is placed over their head.  The bubble is
clear (see-through) and ventilated (room air is pumped through it).  The bubble is also very,
very light and easy to remove.
 


Page 30 of 44
 
30
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
 
   
   
5  
Radioisotopes/radiation-producing machines(e.g., X-rays, CT scans, fluoroscopy).
Body Composition
The risks associated with the DEXA are very low.  The maximum radiation dose you will receive
in this study is less than 1/1000th of the federal and state occupational whole body dose limit
allowed to radiation workers (5,000 mrem).  Put another way, the maximum dose from any scan
we utilize with this DEXA ranges from 1.2 mrem (Whole body scan) to 12.2 mrem (for several of
the regional scans, such as lumbar, femur, and forearm scans).  The average annual
background radiation you already receive is at least 620 mrem/year.  The more radiation you
receive over the course of your life, the more the risk increases of developing a fatal cancer or
inducing changes in genes.  The radiation in this scan is not expected to significantly increase
these risks, but the exact increase in such risks is not known.  There are no discomforts
associated with this procedure. Women who are or could be pregnant should receive no
unnecessary radiation and should not participate in this study.
 
 
c)      
For the following categories, include an estimate of the potential risk, if applicable.
 
 
   
   
1.   
Physical well-being.
Subjects are provided with the following information pertaining to risks to physical well-being:
Body Composition
The risks associated with the DEXA are very low.  The maximum radiation dose you will receive
in this study is less than 1/1000th of the federal and state occupational whole body dose limit
allowed to radiation workers (5,000 mrem).  Put another way, the maximum dose from any scan
we utilize with this DEXA ranges from 1.2 mrem (Whole body scan) to 12.2 mrem (for several of
the regional scans, such as lumbar, femur, and forearm scans).  The average annual
background radiation you already receive is at least 620 mrem/year.  The more radiation you
receive over the course of your life, the more the risk increases of developing a fatal cancer or
inducing changes in genes.  The radiation in this scan is not expected to significantly increase
these risks, but the exact increase in such risks is not known.  There are no discomforts
associated with this procedure. Women who are or could be pregnant should receive no
unnecessary radiation and should not participate in this study.
Exercise Tests
There is a very small chance of an irregular heartbeat during exercise (< 1% of all subjects).
Other rare risks of a stress test are heart attack (< 5 in 10,000) and death (<2 in 10,000).
Wearing a mouthpiece and nose-clip can sometimes cause dryness in the mouth and mild
discomfort. Difficult exercise may make you feel very tired, light headed and nauseous.
Exhausting exercise will, by definition, make you feel very tired.  After any exercise your
muscles might ache.


Page 31 of 44
 
31
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Blood Collection
When the needle goes into a vein, it may hurt for a short period of time (a few seconds).  Also
there may be minor discomfort of having the needle/plastic tube taped to your arm.  In about 1
in 10 cases, a small amount of bleeding will occur under the skin that will cause a bruise.  The
risk of forming a blood clot in the vein is about 1 in 100, and the risk of significant blood loss is 1
in 1,000.  Additionally, there is a risk that you may faint while having blood collected or having
the catheter inserted in your vein.
Resting Metabolic Rate
The risks associated with this measurement are very low.  Some people might feel
claustrophobic (fear of small places) when the bubble is placed over their head.  The bubble is
clear (see-through) and ventilated (room air is pumped through it).  The bubble is also very,
very light and easy to remove.
 
 
   
   
2.   
Psychological well-being.
N/A
 
 
   
   
3.   
Economic well-being.
N/A
 
 
   
   
4.   
Social well-being.
N/A
 
 d) 
In case of overseas research, or working with a specific race/ethnicity in the United States, provide
background on what experience the Investigator(s) have with the proposed population. Describe
qualifications/preparations that enable the Investigator(s) to evaluate cultural appropriateness and
estimate/minimize risks to subjects.
N/A
 
 e) 
Special Precautions. Describe the planned procedures for protecting against or minimizing potential risks. If
appropriate, include the standards for termination of the participation of the individual subject. Discuss
plans for ensuring necessary medical or professional intervention in the event of adverse effects to the
subjects.
N/A


Page 32 of 44
 
32
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
 
 f) 
Data Safety Monitoring                                                                                          
    
N
Is there a Data Safety Monitoring Board (DSMB)?
 
 
   
   
   
If yes, describe its role and indicate who set up the Data Safety Monitoring Board (e.g., sponsor
or Protocol Director).
 
 
   
   
   
Describe the data and safety monitoring plan developed to ensure the safety of participants and
the validity and integrity of research data. Monitoring should be commensurate with risks and
with the size and complexity of the trials.
---------------------------------------------------------------------------------------------
* * * Benefits, Procedures to Maintain Confidentiality * * *
 
 
10. Benefits (Input N/A if not applicable)
a)
Describe the potential benefit(s) to be gained by the subjects. If there is no direct benefit to the subjects
describe how the results of the study may benefit society or a particular group.
The benefits of participation in this study may include: benefits from nutrition; the patient population in
general may benefit from the knowledge provided by the results of this study.
 
11. Procedures to Maintain Confidentiality
a)
Describe the procedures that protect the privacy of the subjects and maintain the confidentiality of the data.
If a linked list is used, explain when the linked list will be destroyed.  Provide a sample of the code that will
be used, if applicable.
Participants will be identified only on a signed consent form and initial screening form that will be kept
locked and separate from other research data. Each subject will be assigned a randomly generated code
(e.g. 12698afd) that will be used to identify them in association with all other research data and blood or
tissue samples. Records identifying individuals will be kept in Dr. Bell’s office/laboratory in a locked cabinet
and will be destroyed (shredded) following completion/publication of the project. Data will only be released
to regulatory/governmental entities authorized to inspect research records, such as the FDA.
 
b)
If information derived from the study will be provided to the subject's personal physician, a government


Page 33 of 44
 
33
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
agency, or any other person or group (other than the research team), describe to whom the information will
be given and the nature of the information, if applicable.
Unless ordered by an agent of the law, no information will be shared specific to a subject without that
subject's written permission. Anonymous data will only be released to regulatory/governmental entities
authorized to inspect research records, such as the FDA.
 
c)
Specify where and under what conditions study data will be kept, how samples will be labeled, who has
access to the data, and what will be available and to whom.  Federal regulations require that study data
and consent documents be kept for a minimum of three (3) years after the completion of the study by the
PI.  For longitudinal projects and federally regulated studies, the PI may be required to keep the data and
documents for a longer time period.
Research records and data will be stored on file in locked cabinets in Dr. Bell’s office/laboratory, or digitally
on a password protected central server. Only members of the research team will have access to these
records. The materials will be archived for a minimum of three years after completion of the project.
---------------------------------------------------------------------------------------------
* * * Potential Conflict of Interest * * *
 
 
12. Potential Conflict of Interest
Although you have already submitted CSU's official Conflict of Interest form (FCOI/COI/COC) to the
University, it is the IRB's responsibility to ensure that conflicting interests related to submitted protocols do
not adversely affect the protection of participants or the credibility of the human research protection program
at CSU. Please answer questions a-d below.  Please note that if you indicate that you have a potential
financial or professional conflict of interest in relation to this protocol, your CSU FCOI/COI/COC Reporting
Form must reflect this potential conflict.  Link to CSU's Conflict of Interest policy:
:http://www.facultycouncil.colostate.edu/files/manual/sectiond.htm#D.7.7
a)
N
In connection with this protocol, do you or any of the protocol investigators or their
immediate family members (i.e., spouse and legal dependents, as determined by the IRS)
have a potential financial or professional conflict of interest?
b)
N/A
If you do have a potential conflict of interest, is this reported in your current
FCOI/COI/COC?
c)
N/A
If you do have a potential conflict of interest, is there a management plan in place to
manage this potential conflict?
d)
N/A
If you do have a potential conflict of interest, is this potential conflict of interest included in
your consent document (as required in the Management Plan)?
 
If you have reported a possible conflict of interest, the IRB will forward the title of this protocol to your Research
Associate Dean to complete your COI file. 


Page 34 of 44
 
34
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
 
For more information on CSU's policy on Conflict of Interest, please see the Colorado State University
Academic Faculty and Administrative Professional Manual Sections D.7.6 & D.7.7.
:http://www.facultycouncil.colostate.edu/files/manual/sectiond.htm#D.7.7
 
Link to CSU's Conflict of Interest Policy: http://www.provost.colostate.edu/index.asp?url=faculty_affairs.
---------------------------------------------------------------------------------------------
* * * Informed Consent * * *
 
 
13. Informed Consent
NOTE: In order to complete this protocol, you must upload either a Consent Form or an Alteration of
Consent Form (i.e., Cover Letter or Verbal Script) OR (if neither of those apply to your project) you must
complete the Waiver of Consent information.
In the space below, please provide consent process background information for each Consent Form(s),
Alteration of Consent Form(s), or Waiver(s).
Informed Consent
  Title
17.7147H Consent Version 01March2018
  Consent Information Type
Consent
  Sponsor's Consent Version Number: (if any)
Consent Form Template
X Attachment
 
17-7147H
Consent.revised.01March2018
<a href='http://ricro.colostate.edu/IRB/ConsentAssentTemplates.html' target=_blank Consent Form
Samples
Who is obtaining consent? The person obtaining consent must be knowledgeable about the study and
authorized by the PI to consent human subjects.
How is consent being obtained?
What steps are you taking to determine that potential subjects are competent to participate in the decision-
making process?


Page 35 of 44
 
35
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------
* * * Assent Background * * *
 
 
14. Assent Background  (Complete if applicable)
All minors must provide an affirmative consent to participate by signing a simplified assent form, unless the
Investigator(s) provides evidence to the IRB that the minor subjects are not capable of assenting because of
age, maturity, psychological state, or other factors.
See sample consent/assent forms at  http://ricro.colostate.edu/IRB/ConsentAssentTemplates.html
Provide assent process background information, in the space below, for each Assent Form, Alteration Form
(i.e., Cover Letter or Verbal Script), and Waiver.
Assent  Background
---------------------------------------------------------------------------------------------


Page 36 of 44
 
36
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
* * * HIPAA * * *
 
 
15. HIPAA
Are you using PHI*? (See definition below)
N
Colorado State University is a hybrid entity and does not have a research-related HIPAA policy. If you will be
working with a HIPAA covered entity (e.g., Poudre Valley Health System), you will need to follow their HIPAA
guidelines. If your project will involve a HIPAA-regulated entity, in the Attachment section (#16) please attach that
entity's required HIPAA consent and/or each waiver of authorization or alteration of authorization requested (e.g.,
waiver of authorization for access to medical records). Include HIPAA authorization language in the consent
document(s) as appropriate (e.g., when enrolling subjects).  
*Protected Health Information (PHI) is health information with one or more of the following identifiers. For
more information see: http://www.hhs.gov/ocr/hipaa/
  1.
Names
  2.
Social Security numbers
  3.
Telephone numbers
  4.
All geographic subdivisions smaller than a State, including street address, city, county, precinct,
zip code, 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
  5.
All elements of dates (except year) for dates directly related to an individual, including birth date,
admission date, discharge date, date of death; and 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
  6.
Fax numbers
  7.
Electronic mail addresses
  8.
Medical record numbers
  9.
Health plan beneficiary numbers
10.
Account numbers
11.
Certificate/license numbers
12.
Vehicle identifiers and serial numbers, including license plate numbers
13.
Device identifiers and serial numbers
14.
Web Universal Resource Locations (URLs)
15.
Internet Protocol (IP) address numbers
16.
Biometric identifiers, including finger and voice prints


Page 37 of 44
 
37
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
17.
Full face photographic images and any comparable images; and
18.
Any other unique identifying number, character, or code (note this does not mean the unique
code assigned by the Investigator(s) to code the research data)
---------------------------------------------------------------------------------------------
* * * Attachments * * *
 
16. Attachments
Attach relevant documents here. These could include: Collaborating Investigator's IRB approval and
approved documents; Conflict of Interest information; Debriefing Script; Grant/Sub-contract; HIPAA
Authorization Form from HIPAA-covered entity; Interview/Focus Group Questions; Investigator's Brochure;
Letters of Agreement/Cooperation from organizations who will help with recruitment; Methodology section of
associated Thesis or Dissertation project; Questionnaires; Radiation Control Office approval material;
Recruitment Material (e.g., flyers, email text, verbal scripts); Sponsor's Protocol; Surveys; Other files
associated with the protocol (you can upload most standard file formats: xls, pdf, jpg, tif, etc.)  Please be
sure to attach all documents associated with your protocol. Failure to attach the files associated with the
protocol may result in this protocol being returned to you for completion prior to being reviewed. Students:
Be sure to attach the Methods section of your thesis or dissertation proposal. If this protocol is associated
with a grant proposal, please remember to attach your grant.
To update or revise any attachments, please delete the existing attachment and upload the revised document to
replace it. 
Document Type
Investigator's Brochure
Attachment
Investigator's Brochure Dapagliflozin Edition 10 (3)
Document Name
Investigator's Brochure Dapagliflozin Edition 10 (3)
Document Type
Other Protocol Material
Attachment
Farxiga Dapagliflozin
Document Name
Farxiga Dapagliflozin
Document Type
Other Protocol Material
Attachment
SGLT2 Dapagliflozin
Document Name
SGLT2 Dapagliflozin
Document Type
Other Protocol Material
Attachment
SGLT2 Inhibitors T2 Diabetes


Page 38 of 44
 
38
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Document Name
SGLT2 Inhibitors T2 Diabetes
Document Type
Other Protocol Material
Attachment
SGLT2 Inhibitors Diabetes
Document Name
SGLT2 Inhibitors Diabetes
Document Type
Other Protocol Material
Attachment
SGLT2 Inhibitors New Diabetes Drug
Document Name
SGLT2 Inhibitors New Diabetes Drug
Document Type
Other Protocol Material
Attachment
Id cards for subjects
Document Name
Id cards for subjects
Document Type
SOP
Attachment
HP-05-R1 Reporting AEs SOP
Document Name
HP-05-R1 Reporting AEs SOP
Document Type
Other Protocol Material
Attachment
FDA safety warning 04Dec2015
Document Name
FDA safety warning 04Dec2015
Document Type
Other Protocol Material
Attachment
CDC Hepatitis B Fact Sheet
Document Name
CDC Hepatitis B Fact Sheet
Document Type
Other Protocol Material
Attachment
NTF Interpretation of Hep B results gjl 29 oct 2015
Document Name
NTF Interpretation of Hep B results gjl 29 oct 2015


Page 39 of 44
 
39
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Document Type
Other Protocol Material
Attachment
14-5531 H Delegation of Authority signed
Document Name
14-5531 H Delegation of Authority signed
Document Type
Questionnaire/Survey
Attachment
Screening Med History 08262015
Document Name
Screening Med History 08262015
Document Type
Sponsor's Protocol
Attachment
Bell 0009 IISR FINAL
Document Name
Bell 0009 IISR FINAL
Document Type
Other Protocol Material
Attachment
FDA-1572 signed
Document Name
FDA-1572 signed
Document Type
Other Protocol Material
Attachment
AZ amemendment concomitant meds
Document Name
AZ amemendment concomitant meds
Document Type
Other Protocol Material
Attachment
Nutritional counseling overview
Document Name
Nutritional counseling overview
Document Type
Investigator's Brochure
Attachment
Investigator's Brochure Dapagliflozin Edition 13
Document Name
Investigator's Brochure Dapagliflozin Edition 13


Page 40 of 44
 
40
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Document Type
Investigator's Brochure
Attachment
Investigator's Brochure Dapagliflozin Edition 12
Document Name
Investigator's Brochure Dapagliflozin Edition 12
Document Type
Debriefing Script
Attachment
14-5531H Participant Study Update Letter
Document Name
14-5531H Participant Study Update Letter
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
17-7147H Example recruitment_Facebook
18Nov2016
Document Name
17-7147H Example recruitment_Facebook
18Nov2016
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
Recruitment_Dapa_Weight Loss
Document Name
Recruitment_Dapa_Weight Loss
Document Type
Sponsor's Protocol
Attachment
Protocol ISSDAP0009 02202017
Document Name
Protocol ISSDAP0009 02202017
Document Type
Questionnaire/Survey
Attachment
17-7147H PI medical screening form 04252017
Document Name
17-7147H PI medical screening form 04252017
Document Type
Questionnaire/Survey
Attachment
3 day food record
Document Name
3 day food record


Page 41 of 44
 
41
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Document Type
Questionnaire/Survey
Attachment
Hunger.Fullness.VAS
Document Name
Hunger.Fullness.VAS
Document Type
Other Protocol Material
Attachment
Copy of Nutritional counseling checklist
Document Name
Copy of Nutritional counseling checklist
Document Type
Other Protocol Material
Attachment
Copy of Nutritional counseling notes
Document Name
Copy of Nutritional counseling notes
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
Recruitment_Dapa_Weight Loss.revisions.6-27-2017
Document Name
Recruitment_Dapa_Weight Loss.revisions.6-27-2017
Document Type
Other Protocol Material
Attachment
17-7147 H AE Report Log 11July2017
Document Name
17-7147 H AE Report Log 11July2017
Document Type
Other Protocol Material
Attachment
Protocol Deviation course of  Antibiotics 26Feb2018
Document Name
Protocol Deviation course of  Antibiotics 26Feb2018
Document Type
Other Protocol Material
Attachment
Protocol Deviation wrong pill bottle 17nov2017
Document Name
Protocol Deviation wrong pill bottle 17nov2017


Page 42 of 44
 
42
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Document Type
Other Protocol Material
Attachment
Protocol Deviation duration of intervention
Document Name
Protocol Deviation duration of intervention
Document Type
Other Protocol Material
Attachment
Protocol Deviation Extended Intervention Period
28Feb2018
Document Name
Protocol Deviation Extended Intervention Period
28Feb2018
---------------------------------------------------------------------------------------------
* * * Obligations * * *
 
 
Obligations (Researcher's Responsibilities)
 
The Principal Investigator is ultimately responsible for the conduct of the project. Obligations of the Principal
Investigator are:
 
Conduct the research involving human subjects as presented in the protocol, including modifications, as
approved by the Department and Institutional Review Board. Changes in any aspect of the study (for example
project design, procedures, consent forms, advertising materials, additional key personnel or subject populations)
will be submitted to the IRB for approval before instituting the changes (PI will submit the "Amendment/Revision"
form);
 
Provide all subjects a copy of the signed consent form, if applicable. Investigators will be required to retain signed
consent documents for three (3) years after close of the study;
 
Maintain an approved status for Human Subjects Protection training. Training must be updated every three (3)
years (Contact RICRO to check your current approval/renewal dates). For more information:  Human Subjects
Training Completed?
 
Submit either the "Protocol Deviation Form" or the "Report Form" to report protocol Deviations/Violations,
Unanticipated Problems (UPs) and/or Adverse Events (AEs) that occur in the course of the protocol. Any of these


Page 43 of 44
 
43
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
Unanticipated Problems (UPs) and/or Adverse Events (AEs) that occur in the course of the protocol. Any of these
events must be reported to the IRB as soon as possible, but not later than five (5) working days.  Note that if an
event resulted in life threatening injury or death OR an event resulted in substantive harm to the safety, rights or
welfare to human subjects, this must be reported to the IRB within 24 hours;
 
Submit the "Continuing Review" Form in order to maintain active status of the approved protocol. This form must
be submitted annually at least four (4) weeks prior to expiration, five (5) weeks for protocols that require full
review. If the protocol is not renewed before expiration, all activities must cease until the protocol has been re-
reviewed;
 
Notify the IRB that the study is complete by submitting the "Final Report" form.
 
  
  
X
The Principal Investigator has read and agrees to abide by the above obligations.
---------------------------------------------------------------------------------------------
* * * Event History * * *
Event History
Date
Status
View Attachments
Letters
02/27/2017
NEW FORM PROTOCOL
CLONED (14-5531H)
03/02/2017
NEW FORM
SUBMITTED
Y
03/06/2017
NEW FORM PANEL
ASSIGNED
03/17/2017
NEW FORM
REVIEWER(S)
ASSIGNED
04/05/2017
NEW FORM
SUBMITTED (CYCLE 1)
Y
04/05/2017
NEW FORM
REVIEWER(S)
ASSIGNED
04/25/2017
NEW FORM
SUBMITTED (CYCLE 2)
Y
04/25/2017
NEW FORM MOVED


Page 44 of 44
 
44
PROTOCOL
Biomedical
Protocol # 17-7147H
 Date Printed: 01/31/2020
Protocol Title:
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For Weight
Loss?
Clinical Research Protocol Title: Dapagliflozin  Promotes Favorable Health Benefits That
Are Independent Of Weight Loss In Overweight/Obese Adults
Protocol Type:
Biomedical
Date Submitted:
03/01/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval. Please check the
comments section of the online protocol.
Questions that appear to not have been answered may not have been required for this submission.
Please see the system application for more details.
----------------------------------------------------------------------------------------------------
04/25/2017
NEW FORM APPROVED
Y
Y
05/02/2017
AMENDMENT 1 FORM
CREATED
05/02/2017
AMENDMENT 1 FORM
SUBMITTED
Y
05/02/2017
AMENDMENT 1 FORM
REVIEWER(S)
ASSIGNED
05/03/2017
AMENDMENT 1 FORM
REVIEWER(S)
ASSIGNED
05/03/2017
AMENDMENT 1 FORM
APPROVED
Y
Y
06/27/2017
AMENDMENT 2 FORM
CREATED
06/27/2017
AMENDMENT 2 FORM
SUBMITTED
Y
06/27/2017
AMENDMENT 2 FORM
APPROVED
Y
Y
02/28/2018
CONTINUING REVIEW 1
FORM CREATED
03/01/2018
CONTINUING REVIEW 1
FORM SUBMITTED
Y
03/16/2018
CONTINUING REVIEW 1
FORM REVIEWER(S)
ASSIGNED
03/23/2018
CONTINUING REVIEW 1
FORM SUBMITTED
(CYCLE 1)
Y
03/25/2018
CONTINUING REVIEW 1
FORM APPROVED
Y
Y
03/26/2018
CONTINUING REVIEW 1
FORM UNDO
APPROVED
03/26/2018
CONTINUING REVIEW 1
FORM APPROVED
Y
Y
03/22/2019
PROTOCOL EXPIRED


Statistical Analysis Plan 
Baseline (pre-counselling) differences between placebo and SGLT2 inhibition groups 
were compared using independent Student t-Tests. Consistent with the experimental design 
(randomized, double-blind, parallel, repeated measures) the influence of SGLT2 inhibition on the 
physiological responses to dietary counselling was examined using two-way (group: placebo vs. 
SGLT2 inhibition x time: before vs. after dietary counselling) analysis of variance (ANOVA). 
The influence of SGLT2 inhibition and dietary counselling on the dynamic responses to oral 
glucose ingestion were examined using three-way ANOVA (placebo vs. SGLT2 inhibition x 
before vs. after dietary counselling x time points during the OGTT). Pairwise multiple 
comparison procedures were performed using the Holm-Sidak Method. Relations of interest 
were described using Pearson product-moment correlations. The level of statistical significance 
was set at P<0.05. Data are reported as mean and standard deviation, unless otherwise indicated. 
Calculations were performed using commercially available statistical software (SigmaStat 3.0, 
Systat Software Inc., San Jose, California, USA). 


Page 1 of 12 Participant’s initials _______ Date _______  
 
 
 
Version: 01March2018 
 
 
 
 
 
 
 
 
CSU#: 17-7147H 
APPROVED: 3/22/2018* EXPIRES: 3/21/2019 
Consent to Participate in a Research Study 
Colorado State University 
 
TITLE OF STUDY: 
 
Does Dapagliflozin Provide Additional Health Benefits To Dietary Counseling For 
Weight Loss?  
 
CO-PRINCIPAL INVESTIGATORS:  
 
Christopher Bell, Ph.D. 
 
 
Christopher L. Melby, Dr.P.H. 
Health & Exercise Science  
 
Food Science & Human Nutrition 
Colorado State University  
 
Colorado State University 
Email: physiology@cahs.colostate.edu Email: chris.melby@colostate.edu 
Telephone: 970-491-3495  
 
Telephone: 970-491-6736 
 
WHY AM I BEING INVITED TO TAKE PART IN THIS RESEARCH? 
 
You are between 18-65 years, weigh more than you prefer (body mass index is greater 
than or equal to 27.5 kg/m2), free of diabetes, not pregnant, and not performing more 
than 30 minutes 3 times per week of moderate exercise.  
 
WHO IS DOING THE STUDY?  
 
Drs. Bell and Melby are running the study; local medical doctors, other researchers, and 
a team of trained graduate and undergraduate students are helping.  AstraZeneca 
Pharmaceuticals LP, a company that makes medicine, is providing financial support for 
the study.   
 
WHAT IS THE PURPOSE OF THIS STUDY?  
 
Dapagliflozin (commercially available as Farxiga; pronounced: far-see-gah) is a 
medicine for treating type 2 diabetes.  Use of Dapagliflozin causes moderate weight 
loss in some, but not all people.  However, Dapagliflozin may have other health 
benefits, including decreased blood pressure, and decreased concentration of 
substances in the blood that are indicative of disease risk (inflammation and oxidative 
stress). It is unclear as to whether these health benefits are due to Dapagliflozin per se, 
weight loss, or a combination of the two.  The purpose of the study is to determine if: 1.  
Dapagliflozin provides additional health benefits to dietary counseling for weight loss?  
2. Use of Dapagliflozin with a calorie-restricted diet can maintain normal control of 
hunger and appetite.  
 
WHERE IS THE STUDY GOING TO TAKE PLACE AND HOW LONG WILL IT LAST?  
 
The study will take place in the Human Performance Clinical Research Laboratory 
(HPCRL) in the Department of Health and Exercise Science and in the Nutrition 


Page 2 of 12 Participant’s initials _______ Date _______  
 
 
 
Version: 01March2018 
 
 
 
 
 
 
 
 
CSU#: 17-7147H 
APPROVED: 3/22/2018* EXPIRES: 3/21/2019 
Laboratory in the Gifford Academic Building, Department of Food Science and Human 
Nutrition, on the main campus of Colorado State University (CSU), Fort Collins. 
 
The study will take place over approximately 2 years. You will be involved for 
approximately 4 months and will be asked to visit the labs 1-2 times per week over 14 
weeks. 
 
WHAT WILL I BE ASKED TO DO? 
 
Here is a brief summary of what you will be asked to do: 
 
Visit 1: in the HPCRL, you will undergo screening: medical history, blood sampling, 
measurement of body composition, and 12-lead electrocardiogram (ECG) and blood 
pressure assessment at rest and during incremental exercise to volitional exhaustion. If 
your screening visits indicate that you qualify for the study, you will be eligible for 
enrollment. 
 
Visit 2: in the HPCRL, your resting metabolic rate (RMR) and blood pressure will be 
measured, and an oral glucose tolerance test (OGTT) will be performed. 
 
Visit 3: in the HPCRL appetite and hunger will be assessed in response to a test meal. 
Afterward, you will be given a form in which you will record the amounts of food and 
beverage you eat and drink for three days (two weekdays and one weekend day).  You 
will return this completed food record to the research team.  This information will be 
useful for the nutrition counselor to understand your current eating habits and to provide 
nutritional recommendations.  
 
Visits 4-27: During the 12 weeks of treatment you will swallow, on a daily basis, either 
Dapagliflozin or placebo. During that time, you will be assigned to a nutrition counselor 
with whom you will meet 1-2 times per week for weigh-ins and to discuss strategies to 
achieve weight loss goals of approximately one pound per week (10-12 pounds at the 
end of 12 weeks). You will need to fast for 10 hours prior to each weigh-in, so these 
meetings typically take place during the morning hours. During these nutrition 
counseling sessions, you will be asked to participate in a variety of educational activities 
to help meet your assigned weight loss goal, such as how to accurately determine food 
portion sizes.  
 
Visit 28: in the HPCRL, your resting metabolic rate (RMR) and blood pressure will be 
measured, and an oral glucose tolerance test (OGTT) will be performed. This visit will 
occur in week 12 (e.g. the final week of daily ingestion of Dapagliflozin or placebo). 
 
Visit 29: in the HPCRL, appetite and hunger will be assessed. This visit will occur in 
week 12 (during the final week of daily ingestion of Dapagliflozin or placebo). Body 
composition will be measured at this visit or the start of the following week (week 13).  
 
 
 


Page 3 of 12 Participant’s initials _______ Date _______  
 
 
 
Version: 01March2018 
 
 
 
 
 
 
 
 
CSU#: 17-7147H 
APPROVED: 3/22/2018* EXPIRES: 3/21/2019 
 
 
Outline and timing of study visits: 
Visits 1-3 
Visits 4-27  
(Weeks 1-12) 
Visits 28-29  
(Week 12) 
Screening 
RMR/ 
OGTT 
Stress 
test 
Appetite and 
hunger 
assessment 
Initiation of treatment (Placebo 
or Dapagliflozin daily, weigh-
ins twice weekly, and nutrition 
counseling once weekly) 
RMR/ 
OGTT 
Appetite and 
hunger 
assessment 
OGTT: Oral glucose tolerance test.  RMR: Resting Metabolic Rate Test 
 
Here is a detailed description of what you will be asked to do: 
 
Visit 1 – Screening Visit: Medical History / Blood Test / Body Composition 
 
The first visit to the HPCRL will be a screening visit. During this visit, we will make sure 
that participation in this study is right for you. 
 
This screening visit will include the following procedures: 
 
Medical Questionnaire 
You will be asked to answer several pages of questions related to your health, any 
illness you may have or have had, and medications you use or have used in the past.  
 
Blood Pressure 
We will measure your blood pressure using a standard blood pressure cuff (the same as 
in a doctor's office). Blood pressure will be measured during all of the tests performed in 
the lab with the exception of body composition. There are no known risks associated 
with this procedure. (Duration: 5 minutes) 
 
Pregnancy Test (Women Only) 
Women who are or could be pregnant should not participate in this study. Before the 
body composition test(s), women will be asked to take a pregnancy test (urine test) to 
confirm they are not pregnant.    
 
Body Composition 
We will measure how much fat you have in your body using a test called dual energy x-
ray absorptiometry (DEXA). The DEXA test requires you to lie quietly on a padded table 
while a small probe gives off low-level x-rays and sends them over your entire body.  
This test gives very accurate measurements of your body fat and bone mineral density.  
We will also measure the circumference of your waist and hip using a tape measure. 
(Duration: ~ 15 minutes) 
 
Blood Test 
During this visit, we will take approximately 20 ml (~1.5 tablespoons) from you; this is a 
lot less than the amount that is typically taken when a person donates blood. Your blood 


Page 4 of 12 Participant’s initials _______ Date _______  
 
 
 
Version: 01March2018 
 
 
 
 
 
 
 
 
CSU#: 17-7147H 
APPROVED: 3/22/2018* EXPIRES: 3/21/2019 
will be tested for various things to make sure you are healthy enough to consume 
Dapagliflozin. Your blood will be taken from veins in your arms or hands using a needle. 
On the advice of the medical monitor (study physician), you may be asked to have your 
blood tested several more times during the treatment period to make sure the study is 
still right for you.  
 
Exercise Stress Test 
You will be asked to perform a vigorous exercise test.  This test will tell us if your heart 
is healthy. You will be asked to walk on a motorized treadmill or ride an exercise cycle 
(cycle ergometer) for approximately 10-15 minutes. The exercise will become more 
difficult every 2 minutes. While you are walking/riding, we will measure your heart rate 
with an electrocardiogram (ECG) and your blood pressure with a cuff placed around 
your upper arm. We will also ask you to wear a nose clip (to stop you breathing through 
your nose) and ask you to breathe through a mouthpiece. This will let us measure the 
gases you breathe. Depending on your age, a physician may supervise the test. If we 
do not think your heart is healthy, you will be referred to your primary care physician for 
further testing. There is a chance that you may not be allowed to take part in our study. 
(Duration: ~ 60 minutes) 
 
The whole visit will last approximately 2 hours. 
 
Visit 2 – Resting Metabolic Rate Test, Oral Glucose Tolerance Test, and Blood 
Pressure 
 
These tests will take place early in the morning after a 12-hour fast and 24-hour 
abstention from alcohol, caffeine, and exercise. You will be asked to wear a T-shirt. 
 
Resting Metabolic Rate 
We will measure how your metabolism works (how many calories you burn) while you 
are resting. You will rest quietly on a bed for 10 minutes. After that time, we will place a 
clear plastic bubble (hood) over your head, through which you will be able to breath, 
and ask you to continue lying quietly for 45 minutes. (Duration: ~ 60 minutes) 
 
Blood Pressure 
We will measure your blood pressure using a standard blood pressure cuff (the same as 
in a doctor's office). We will do this three times. (Duration: 5 minutes) 
 
Oral Glucose Tolerance Test (OGTT) 
We will then perform the oral glucose tolerance test. You will be asked to drink water 
(300 ml or ~ 10 oz) in approximately 5 minutes. A small amount of sugar (75 g of 
glucose) will have been added to the water. This will make it taste sweeter and also 
increase your blood sugar.   
 
After drinking the water you will sit/lie quietly for 2 hours. You will be able to read, watch 
TV, and/or listen to music. We will collect blood from you over the 2 hours. Your blood 
will be analyzed for concentrations of sugar (glucose), insulin (something that helps 
control blood sugar), and other things that may help control blood sugar. Your blood will 


Page 5 of 12 Participant’s initials _______ Date _______  
 
 
 
Version: 01March2018 
 
 
 
 
 
 
 
 
CSU#: 17-7147H 
APPROVED: 3/22/2018* EXPIRES: 3/21/2019 
be taken from veins in your arms or hands using needles and hollow plastic tubes called 
catheters. 
 
The whole visit will last approximately 3 hours. 
 
Visit 3 – Appetite and Hunger Assessment 
 
This test will take place early in the morning after a 12-hour fast, and 24-hour abstention 
from alcohol, caffeine, and exercise. You will be asked to wear a T-shirt. 
 
We will place a hollow plastic tube (a venous catheter) into a vein in your arm or hand.  
The tube will remain in your vein for approximately 5 hours. We will sample a very small 
amount of blood periodically throughout the duration of the visit. The total amount of 
blood sampled will be approximately 100 ml, or 7 tablespoons. 
 
You will be given a liquid meal (an Energy Drink) to serve as “an appetizer” before you 
are given your main meal. One hour later, you will be presented with a buffet style 
presentation of assorted foods and beverages. You will be able to eat as much, or as 
little, as you like of any or all of the foods and beverages.   
 
Throughout the visit (before the liquid meal, and before and after the main meal) you will 
be asked questions about your hunger and appetite. 
 
Your blood pressure will also be measured periodically throughout the duration of the 
visit. 
 
The whole visit will last approximately 5.5 hours. 
 
Visit 4-27 – 12 Weeks of Nutritional Counseling  
 
You will be randomly assigned to receive either the medicine Dapagliflozin or the 
placebo for 12 weeks and you will be given dietary counseling for weight loss. The goal 
of the counseling is to help you moderately reduce your calorie intake to produce weight 
loss of about one pound per week.  You will not know if you are assigned to take 
Dapagliflozin or the placebo: 
 
Condition 1) You will swallow Dapagliflozin every day. 
 
Condition 2) You will swallow a placebo (a pill that has no effect) every day. 
 
Regardless of the condition to which you are assigned, you will meet with your 
nutritional counselor 1-2 times per week for the remainder ot the study as described 
below. 
 
During the first 6 weeks you will meet with your study counselor 2 times per week for 
dietary counseling and measurement of body weight.  During the second 6-week period 


Page 6 of 12 Participant’s initials _______ Date _______  
 
 
 
Version: 01March2018 
 
 
 
 
 
 
 
 
CSU#: 17-7147H 
APPROVED: 3/22/2018* EXPIRES: 3/21/2019 
you may continue to meet 1-2 times per week for dietary counseling and body weight 
measurement, depending on whether or not you are achieving your weight loss goals. If 
you are losing weight as prescribed, you will meet only once per week, but if you are not 
achieving your weight loss goals you will meet 2 times per week.  You will need to fast 
for 10 hours prior to the weigh-in. On 2 random counseling occasions between weeks 4 
and 10, you will be asked to recall what you ate during the previous 24 hours. (Duration: 
15-30 minutes).  If you fail to achieve your target body weight (within 2 pounds) on three 
consecutive weighing sessions, you will be provided with additional counseling and 
instructions to aid in achieving your target body weight.  If you fail to attend a minimum 
of 80% of your appointments you will be removed the study. 
 
During the 12 weeks of your study participation, you will swallow a pill every day. The 
pill may be Dapagliflozin or a placebo, a pill that has no effect. You will not know which 
pill you are swallowing.  If you are chosen to swallow Dapagliflozin, for the first 2 weeks 
the dose will be 5 mg/day. For the next 10 weeks, the dose will be 10 mg/day. For a 
description of Dapagliflozin, see below. 
 
If you fail to ingest 90% of your medication (75 of 84 total doses), you will be removed 
from the study.  
 
Visit 28 – Resting Metabolic Rate Test, Oral Glucose Tolerance Test, and Blood 
Pressure 
 
You will repeat the procedures described in visit 2. This visit will occur in week 12 (e.g. 
the final week of daily ingestion of Dapagliflozin or placebo). (Duration: ~ 3 hours) 
 
Visit 29 – Appetite and Hunger Assessment  
 
You will repeat the procedures described in visit 3. You will also undergo measurement 
of body composition (as described in visit 1) and be asked to complete the 3-day food 
record again, which you will return to the research team. This visit will occur in week 12 
(e.g. the final week of daily ingestion of Dapagliflozin or placebo). (Duration: ~ 5.5 
hours) 
 
 
WHAT IS DAPAGLIFLOZIN? 
 
Dapagliflozin is a new medicine that is used to treat people who have type 2 diabetes 
(high blood sugar and/or difficulty controlling blood sugar). Dapagliflozin works by 
limiting the body’s ability to absorb sugar from food and beverages.  It does this by 
changing the ability of the kidneys to absorb sugar.  The sugar that is not absorbed is 
removed from the body in urine. 
 
ARE THERE REASONS WHY I SHOULD NOT TAKE PART IN THIS STUDY?  
 
You will not be allowed to take part in the study for any of the following reasons: 


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1. Evidence of serious (clinically significant) heart (cardiovascular), lung (respiratory), 
kidney (renal), liver (hepatic), stomach (gastrointestinal), blood (hematological), nerve 
(neurological), mental (psychiatric), or other disease, or if you have been hospitalized in 
the past 2 years as a result of these conditions, or are receiving medicine 
(pharmacological treatment) for these conditions.  
 
2. Use of prescription drugs (see exceptions listed below) or herbal preparations in the 
2 weeks before study commencement. Prior use of medication or herbal preparations in 
the 4 weeks before study commencement that are intended for weight-loss and/or 
sold/marketed as weight-loss products or may alter metabolism. 
 
Permitted Prescription Drugs: 
• Birth Control  
• Less than a 10-day short course of antibiotics. Antibiotics prescribed for any 
serious condition will be reviewed on case by case basis no matter the course 
prescribed.   Note: Rifampicin is not permitted. 
• Other medicines, such as those for GERD, depression, OTC analgesics, and 
allergy medications may be allowed but will be approved on a case-by-case basis. 
 
3. You are currently enrolled in another clinical study for another investigational drug or 
have taken any other investigational drug within 30 days before the screening visit. 
 
4. You are a smoker: Habitual and/or recent use (within 2 years) of tobacco. 
 
5. You are considered unsuitable for participation in this trial for any reason, as judged 
by the investigator or medical monitor. 
 
6. You have a history of serious hypersensitivity reaction to Dapagliflozin. 
 
7. You have severe kidney problems: renal impairment, end-stage renal disease, or 
dialysis. 
 
8. You are pregnant or breastfeeding.  
 
9. You have severe hepatic insufficiency and/or significant abnormal liver function 
based on blood tests. 
 
10. You have a history of bladder cancer. 
 
11. Your blood pressure during visit 1: Systolic blood pressure ≥160 mmHg and/or 
diastolic blood pressure ≥100 mmHg. 
 
12. Your blood pressure during visit 4: Systolic blood pressure ≥160 mmHg and/or 
diastolic blood pressure ≥100 mmHg 
 


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13. Patients who, in the judgment of the medical doctor, may be at risk for dehydration. 
    
14.  You have a history of bone fractures due to fragile bones and/or the results of your 
DEXA scan indicate results consistent with fragile/weak bones (osteopenia). 
 
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS?  
 
It is not possible to identify all potential risks in research procedures, but the 
researcher(s) have taken reasonable safeguards to minimize any known and potential 
(but unknown) risks. The Human Performance Clinical Research Laboratory has 
emergency supplies including a medicine trolley equipped with heart machines and 
supplemental oxygen. The research team has a great deal of experience with all of the 
procedures. Some of the procedures for which you are being asked to volunteer have a 
number of associated risks: 
 
Body Composition 
The risks associated with the DEXA are very low. The maximum radiation dose you will 
receive in this study is less than 1/1000th of the federal and state occupational whole 
body dose limit allowed to radiation workers (5,000 mrem). Put another way, the 
maximum dose from any scan we utilize with this DEXA ranges from 1.2 mrem (Whole 
body scan) to 12.2 mrem (for several of the regional scans, such as lumbar, femur, and 
forearm scans). The average annual background radiation you already receive is at 
least 620 mrem/year. The more radiation you receive over the course of your life, the 
more the risk increases of developing a fatal cancer or inducing changes in genes. The 
radiation in this scan is not expected to significantly increase these risks, but the exact 
increase in such risks is not known. There are no discomforts associated with this 
procedure. Women who are or could be pregnant should receive no unnecessary 
radiation and should not participate in this study. 
 
Blood Collection 
When the needle goes into a vein, it may hurt for a short period of time (a few seconds).  
Also, there may be minor discomfort of having the needle/plastic tube taped to your 
arm. In about 1 in 10 cases, a small amount of bleeding will occur under the skin that 
will cause a bruise. The risk of forming a blood clot in the vein is about 1 in 100, and the 
risk of significant blood loss is 1 in 1,000. Additionally, there is a risk that you may faint 
while having blood collected or having the catheter inserted in your vein. 
 
Exercise Test 
There is a very small chance of an irregular heartbeat during exercise (< 1% of all 
subjects). Other rare risks of a stress test are heart attack (< 5 in 10,000) and death (<2 
in 10,000). Wearing a mouthpiece and nose-clip can sometimes cause dryness in the 
mouth and mild discomfort. Difficult exercise may make you feel very tired, light-headed, 
and nauseous. Exhausting exercise will, by definition, make you feel very tired. After 
any exercise, your muscles might ache. 
 
Resting Metabolic Rate 


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The risks associated with this measurement are very low. Some people might feel 
claustrophobic (fear of small places) when the bubble is placed over their head. The 
bubble is clear (see-through) and ventilated (room air is pumped through it). The bubble 
is also very, very light and easy to remove.  
 
Dapagliflozin 
Adverse reactions in placebo-controlled studies reported in more than 2% but less than 
8.5% of patients treated with Dapagliflozin include:  
 
• Vaginal yeast infections including vaginal odor, white or yellowish vaginal 
discharge (discharge may be lumpy or look like cottage cheese), or vaginal 
itching..  
 
• Stuffy or runny nose and sore throat (nasopharyngitis) 
 
• Urinary tract infections (UTIs), such as bladder or kidney infection. 
 
• Low blood pressure (hypotension) which may cause you to feel dizzy, faint, 
lightheaded, or weak: this is particularly in persons with impaired kidney function, 
elderly, or persons on certain diuretics. In order to minimize this risk, we are not 
enrolling people who may be increased risk of hypotension. 
 
• Impaired kidney function: this risk is increased in certain populations. In order to 
minimize this risk, we are not enrolling people who may be at increased risk and 
we are screening your kidney function prior to and during participation.  
 
• Back pain 
 
• Increased urination 
 
• Yeast infection of the skin around the penis. 
 
• Influenza (flu) 
 
• Nausea (upset stomach) 
 
• An Increase in bad cholesterol (LDL) 
 
• Constipation 
 
• Discomfort with urination 
 
• Pain in the extremities 
 
In a study of 5,936 patients with type 2 diabetes, one patient became ill with diabetic 
ketoacidosis (a metabolic sickness). If you experience any of the following 


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sensations/symptoms, you should seek immediate medical help and contact the 
investigator: sickly or queasy (nausea), vomiting, stomach (abdominal) pain, confusion, 
change in breathing pattern, and unusual tiredness (fatigue) or sleepiness. 
 
In addition, use of Dapagliflozin is also associated with modest weight loss (up to 10 lbs 
over 12 weeks) in some people. 
 
ARE THERE ANY BENEFITS FROM TAKING PART IN THIS STUDY?  
 
There are no direct benefits in participating; however, you will receive a copy of your 
results and information pertinent to your body composition (i.e. height and weight) and 
metabolic and cardiovascular risk factors. For example, in blood we will measure 
concentrations of glucose. You will be provided with a copy of your DEXA scan; you may 
wish to have this interpreted by a medically qualified professional. Finally, this study has 
the potential to identify an additional benefit for people who use Dapagliflozin to treat 
their type 2 diabetes.   
 
DO I HAVE TO TAKE PART IN THE STUDY? 
 
Your participation in this research is voluntary. If you decide to participate in the study, 
you may withdraw your consent and stop participating at any time without penalty or 
loss of benefits to which you are otherwise entitled.   
 
WHAT WILL IT COST ME TO PARTICIPATE?  
 
Other than transport to and from the campus, your participation should incur no costs.   
 
WHO WILL SEE THE INFORMATION THAT I GIVE?  
 
We will keep private all research records that identify you, to the extent allowed by law.  
For this study, we will assign a code to your data (e.g. 1234ABCD), so the only place 
your name will appear in our records is on the consent form and in our data spreadsheet 
that links you to your code. Only the research team will have access to the link between 
you, your code, and your data. The only exceptions to this are if we are asked to share 
the records of the study for audit purposes with the Food and Drug Administration, 
Health and Human Services, AstraZeneca, and/or the CSU Institutional Review Board 
ethics committee, if necessary. In addition, for funded studies, the CSU financial 
management team may also request an audit of research expenditures. For financial 
audits, only the fact that you participated would be shared, not any research data. When 
we write about the study to share it with other researchers, we will write about the 
combined information we have gathered. You will not be identified in these written 
materials. We may publish the results of this study; however, we will keep your name 
and other identifying information private. 
 
Your identity/record of receiving compensation (NOT your data) may be made available 
to CSU officials for financial audits. 


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CAN MY TAKING PART IN THE STUDY END EARLY?  
 
You will be weighed twice per week in the Gifford Building. If you fail to achieve your 
target body weight (within 2 pounds) on three consecutive weigh-in sessions you will be 
provided with additional counseling and instruction to aid in achieving your target body 
weight. If you fail to ingest 90% of your Dapagliflozin or placebo (75 of 84 total doses), 
you will be removed from the study. Your participation in the study will end if you 
become pregnant. We ask that, in the event that you do become pregnant, you 
immediately notify study staff and stop taking the provided pills. 
 
WILL I RECEIVE ANY COMPENSATION FOR TAKING PART IN THIS STUDY?  
 
If you complete all of the visits and all of the procedures as described for the entire 
study, you will receive up to $400 in total compensation. $300 will be paid in installments 
and prorated as follows: you will not receive compensation for visit 1 (the screening visit). 
You will receive $60 following completion of baseline testing (visits 2 and 3).  After 
successfully completing 8 weeks of the counseling, you will receive $60; after completing 
12 weeks of counseling, you will receive $60.  You will receive $60 for completion of visit 
28 and $60 for completion of visit 29. If you are at least 95% compliant both in terms of 
visit attendance and pill ingestion, you will receive an additional $100 for a total of $400 
for your participation.    
 
Should your participation in the study end early, you will still receive feedback pertaining 
to your health.   
 
WHAT HAPPENS IF I AM INJURED BECAUSE OF THE RESEARCH?  
 
We will arrange to get you medical care if you have an injury that is caused by this 
research.  
 
CSU will pay for medical expenses for the treatment of a personal injury that is a direct 
result of the administration of the study drug (CSU will be reimbursed by AstraZeneca). 
CSU will not provide compensation for lost wages or for any other damages, expenses 
or losses, or for medical expenses that have been covered by medical insurance.  
 
Should you sustain an injury that is not the direct result of the study drug, you or your 
insurance company may have to pay for the required care. The Colorado Governmental 
Immunity Act determines and may limit Colorado State University, University of 
Colorado Denver, and University of Colorado Hospital’s legal responsibility if an injury 
happens because of this study. Claims against the University must be filed with 
Colorado State University within 180 days of the injury. 
 
WHAT IF I HAVE QUESTIONS?       
 


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Before you decide whether to accept this invitation to take part in the study, please ask 
any questions that might come to mind now.  Later, if you have questions about the 
study, you can contact the investigators via email: 
 
Dr. Melby - chris.melby@colostate.edu  
Dr. Bell - physiology@cahs.colostate.edu 
 
 
If you have any questions about your rights as a volunteer in this research, contact the 
CSU IRB at: RICRO_IRB@mail.colostate.edu; 970-491-1553. We will give you a copy of 
this consent form to take with you. 
 
WHAT ELSE DO I NEED TO KNOW?  
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This website will not include information that can identify you. At 
most, the Web site will include a summary of the results. You can search this website at 
any time.   
 
Your signature acknowledges that you have read the information stated and willingly 
sign this consent form.  Your signature also acknowledges that you have received, on 
the date signed, a copy of this document containing   12    pages. 
 
___________________________________________ 
 
_____________ 
Signature of person agreeing to take part in the study  
 
Date 
 
 
_____________________________________________  
_____________ 
Printed name of person agreeing to take part in the study  
Time of Day 
 
 
_________________________________________ 
 
 
_____________ 
Printed name of person providing information to participant 
Date 
 
 
_________________________________________    
Signature of research staff