Clinical trial NCT02552355
Conditions: Physical Activity
Sponsor: Colorado State University
Start date: 2015-08-01; Completion date: 2017-08-01
Enrollment: 56 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators propose that post-exercise milk protein feeding will enhance the mitochondrial protein synthesis (biogenesis) response to an exercise-training program. In addition, the investigators propose that this stimulatory effect of protein feeding will overcome the potential blunting effect of metformin on exercise responses. The investigators will investigate these outcomes over a 12-week exercise-training program in older adults with pre-diabetes with or without metformin treatment.

Detailed description:
This is a randomized, placebo controlled, double blind study. 60 men and women over the age of 55 with indications of pre-diabetes will be recruited for participation and randomly assigned to one of four 12 week exercise training programs: 1)Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of Metformin. 2) Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of Metformin. 3) Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of matching placebo. 4) Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of placebo.

Daily administration of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4 during a 12 week exercise training program. The titration dosing scheme and taking metformin/placebo with meals will help reduce the most common side effects (i.e.,gastrointestinal discomfort). If participants experience gastrointestinal discomfort, the dose will be lowered to 1500 mg/day.

Arms: arm 1: Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4. Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of Metformin. arm 2: Daily oral administration of matching placebo with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of matching placebo will begin as one tablet for the first week and will increase by one tablet/day/week until reaching 4 tablets by week 4. Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of matching placebo. arm 3: Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week. Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of Metformin arm 4: Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week. Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of placebo.
Interventions: intervention 1: Metformin intervention 2: Placebo intervention 3: Carbohydrate Beverage intervention 4: Protein Beverage
Intervention descriptions: intervention 1: Daily administration of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4 during a 12 week exercise training program. intervention 2: Daily administration of matching placebo during a 12 week exercise training program. intervention 3: Supervised aerobic exercise 3 days per week followed by a carbohydrate drink intervention 4: Supervised aerobic exercise 3 days per week followed by a protein drink

Protocol documents:
Prot_SAP_000.pdf: 
 
PROTOCOL
Biomedical
Colorado State
University
Protocol # 15-5837H
 Date Printed: 11/05/2018
Amendment
1
Personnel Information
1
Subject Population
3
Study Location
3
General Checklist
3
Funding
5
Expedited Paragraphs
6
Purpose,Study Procedures,Background
7
Radioisotopes or Radiation Machines
11
Medical Equipment for Human Subjects and Laboratory Animals; Investigatiional Devices
12
Drugs, Reagents, or Chemicals
12
Subject Population (a-g)
13
Subject Population (h-m)
14
Risks
16
Benefits, Procedures to Maintain Confidentiality
20
Potential Conflict of Interest
20
Informed Consent
21
Assent Background
22
HIPAA
22
Attachments
23


 
PROTOCOL
Biomedical
Colorado State
University
Protocol # 15-5837H
 Date Printed: 11/05/2018
Obligations
29
Event History
29


Page 1 of 33
 
1
PROTOCOL
Biomedical
Colorado State
University
Protocol # 15-5837H
 Date Printed: 11/05/2018
Protocol Title:
Milk protein feeding after aerobic exercise in older adults with pre-diabetes taking the
biguanide metformin
Protocol Type:
Biomedical
Date Submitted:
10/04/2018
Approval Period:
10/04/2018-05/13/2019
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.
----------------------------------------------------------------------------------------------------
* * * Amendment * * *
 
 
Amendment (1. Complete this one-page form, 2.  Update the sections of your protocol that you are requesting to
amend, 3. Electronically "sign" your application by clicking the check box on the Obligations page, 4. Remember
to click "Submit Form" so that the IRB administrators receive your request.)
 
  
  
1. 
Summarize the proposed changes to the protocol in lay terms.
Change of principal investigator to Karyn Hamilton.
 
 
 
Proceed to the appropriate section(s) of the protocol and make your changes.
 
 
 
IMPORTANT NOTE ON AMENDING ATTACHED DOCUMENTS:  If you are requesting to amend a
file that has been previously attached and approved, you MUST:  1.  Delete the file that is currently
attached,  2. Browse on your computer,  and  3. Upload the revised file that you are requesting to use.
 
  
  
2. 
Indicate level of risk involved with the changes proposed.
(If level of risk has changed, please update the section 'Risks' in the protocol information.)
 
   
No Change
 
  
  
Approval Includes
 
  
  
3. 
List of sections (and questions) that have been changed/modified
---------------------------------------------------------------------------------------------
* * * Personnel Information * * *
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
Degree
Title


Page 2 of 33
 
(Faculty, Staff or Postdoc)
Hamilton, Karyn
Professor
Email
Phone
Fax
Karyn.Hamilton@ColoState.EDU
(970) 491-3961
Department Name
Campus Delivery Code
 
244
 
 Human Subjects Training Completed? PIs must complete training every three
(3) years.
Y
 
 
 
Department Head  Mandatory
Name of Department Head
Degree
Title
Braun, Barry
Ph.D.
Professor
Email
Phone
Fax
Barry.Braun@colostate.edu
(970)491-7875
Department Name
Campus Delivery Code
 
1582 Dept Hlth & Exer Sci
1582
 
 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.
Y
 
Administrative Contact
Name of Administrative Contact,
Project Director, or Lab Coordinator
Degree:
Title
Biela, Laurie
BS
Research Associate III
Email
Phone
Fax
Laurie.Biela@colostate.edu
970-491-2242
970-491-0445
Department Name
Campus Delivery Code
 
1582 Dept Hlth & Exer Sci
1582
 
 Human Subjects Training Completed? Training is not required for
Administrative Contacts
Y
No training data is available.
 
Other Researcher or Key Personnel
Name of Other Researcher (NOTE:
Anyone listed in this role will have
View Mode access only)
Degree
Title
Leach, Heather
Assistant Professor
Email
Phone
Fax
Heather.Leach@colostate.edu
Department Name
Campus Delivery Code (CSU) or off-
campus mailing address
 
244
 
 Human Subjects Training Completed? Training is required for all Key
Personnel on NIH grants. Training must be updated every three (3) years.
Y


Page 3 of 33
 
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
X
Elderly
 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)
       
---------------------------------------------------------------------------------------------
* * * 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 * * *


Page 4 of 33
 
 
General Checklist
         Select All That Apply :
X
Proposed Start Date (cannot be before IRB approval):
July 1, 2015
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)
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
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)
X
 Commercially available drugs, reagents, or other chemicals administered to subjects (even if they are not
being studied)
X
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)


Page 5 of 33
 
---------------------------------------------------------------------------------------------
* * * 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 #
121860
Sponsor's ID # (If known)
Funded By
Other
 
Dairy Management Inc.
Principal Investigator
Benjamin Miller
Grant/Contract Title if different from Protocol Title
Milk Protein Feeding After Aerobic Exercise in Older
Adults with Pre-Diabetes Taking the Biguanide
Metformin
For Federal projects, are contents of this protocol the
same as described in Federal proposal application?
N
Is this an Umbrella protocol?
N
Is this protocol under an Umbrella protocol?
Funding Administered By
UNIVERSITY
CSU PASS #
Sponsor's ID # (If known)
Funded By
Other
 
Dexcom Inc.
Principal Investigator
Grant/Contract Title if different from Protocol Title
For Federal projects, are contents of this protocol the
same as described in Federal proposal application?
Is this an Umbrella protocol?
Is this protocol under an Umbrella protocol?
Funding - Fellowships


Page 6 of 33
 
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.)
 
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


Page 7 of 33
 
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.
 
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)
   
Title (Please indicate if the protocol title is different from the proposal title)
Milk protein feeding after aerobic exercise in older adults with pre-diabetes taking the biguanide metformin
 
      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.
We propose that post-exercise milk protein feeding will enhance the mitochondrial protein synthesis
(biogenesis) response to an exercise-training program. In addition, we propose that this stimulatory effect
of protein feeding will overcome the potential blunting effect of metformin on exercise responses. We will
investigate these outcomes over a 12-week exercise-training program in older adults with pre-diabetes
with or without metformin treatment.
Sub-study:
1. CGM in Individuals with prediabetes undergoing an exercise-training program with or without Metformin.
2. CGM in healthy control individuals to compare to individuals with prediabetes.


Page 8 of 33
 
 
b)
What does the Investigator(s) hope to learn from the study?
We hope to:
a) provide the first evidence that post-exercise milk protein supplementation is effective in diseased
population (i.e., older adults with pre-diabetes) and those on medications (i.e., metformin).
b) demonstrate that the potential inhibitory effects of metformin on aerobic exercise adaptations can be
opposed by milk protein feeding.
Sub-study
1. Glucose Profiles via CGM in pre diabetic individuals before, during and after the intervention (i.e.,
aerobic exercise training with or without metformin with post-exercise carbohydrate or
carbohydrate+protein feeding as listed below in 2a).
2: Glucose profiles via CGM in healthy individuals. Healthy individuals will complete baseline procedures
but will not complete an intervention.
 
c)
Proposed Start Date (may not precede IRB approval date):
August 1, 2015
 
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).
Study Overview:
Pre-diabetic and healthy participants will first undergo a medical questionnaire, resting ECG, graded
exercise test with ECG and assessment of VO2max, anthropometric measurement (height, weight and
body composition by DEXA scanning), an oral glucose tolerance test (OGTT), and a muscle biopsy.
Prediabetic participants will be screened to eliminate those lactose intolerant, medications known to affect
the primary outcomes, medications or recent procedures contraindicated with metformin  or not pre-
diabetic. Subjects who meet these criteria will be randomized so that subject characteristics are matched
between groups, while the study team and participants will remain blinded to treatment (i.e., randomized,
double-blind study design). Subjects will be assigned to exercise + carbohydrate + placebo, exercise +
protein + placebo, exercise + carbohydrate + metformin, or exercise + protein + metformin.
A minimum of two days apart from the VO2max test, skeletal muscle will be sampled from pre-diabetic and
healthy participants. During these visits, pre-diabetic subjects will have the option to participate in a study
to test the impact of one counseling session on physical activity after completion of the exercise training
and to identify individual, socio-cultural and environmental determinants of physical activity 12 weeks after
the end of the exercise intervention. If the subjects wish to participate they will complete questionnaires to
measure sociodemographic information, physical activity, self-efficacy, planning, self-regulation and
outcome expectancy of exercise, and perceptions of neighborhood support at baseline, completion of
exercise training and 12 weeks after the exercise training.
Pre diabetic and healthy participants will also have the option to participate in a study to wear a Dexcom
generation 6 (G6) continuous glucose monitor (CGM) to measure glucose values every 5 minutes. Healthy
participants will wear the device once for up to 10 consecutive days. Pre-diabetic participants will wear the
device for up to 10-consecutive days at three different time points: before, during and after the 12-week
exercise intervention for a total of 30 days wearing the CGM. The Dexcom G6 CGM is for investigational
use only and is not FDA approved. The G6 is modeled after commercially available, FDA approved CGM
devices. The differences between the G6 and commercially available devices are a reduced calibration
scheme, meaning less finger stick blood glucose measurements for calibration;  a longer wear for up to 10
days for the G6 vs. 7 days for commercially available product. Last, commercially available devices could
give false high glucose readings if individuals took acetaminophen. The G6 sensor contains updated
sensor technology aimed to block the interference of acetaminophen.
After randomization into placebo or metformin groups, the pre-diabetic subjects will begin a 12-wk exercise


Page 9 of 33
 
intervention consisting of 3 days per week of aerobic exercise training with post-exercise consumption of a
20 gram protein beverage or isocaloric carbohydrate beverage. We have completed this supplementation
protocol in previous studies and a currently ongoing investigation.
At the 8-wk time point, pre-diabetic subjects will begin the daily consumption of heavy water (D2O) for the
assessment of mitochondrial and individual protein synthesis. At the completion of the training period, the
pre-diabetic subjects will repeat all assessments performed prior to training including the DEXA, VO2max,
OGTT and muscle sample. Muscle samples obtained pre- and post-training will be used to evaluate
mitochondrial function using high-resolution respirometry, western blot analysis, and stable isotope
incorporation (post only).
Healthy participants will complete the medical history questionnaire, resting ECG, graded exercise testing
(ECG and VO2max), DEXA, OGTT, CGM, and muscle biopsy.
Detailed Procedures:
Oral glucose tolerance test (OGTT): An OGTT is the most common clinical procedure to determine
impaired glucose tolerance and indices of insulin sensitivity. First, an intravenous catheter will placed in an
arm or hand vein to obtain blood samples for analysis of plasma glucose and glucoregulatory hormones.
Blood will be sampled before, 5, 10, 20, 30, 45, 60, 90, and 120 min after completing the consumption of
75 gram glucose beverage. The fasted blood sample will also be used for a blood chemistry panel that
includes electrolytes, glucose, in addition to kidney and liver related variables (including creatinine, eGFRif
AFR AMER, eGFR, Albumin, Bilirubin, Alk Phos, AST, Uric Acid, ALT, A/G ratio, etc.).Subjects will not be
allowed to participate until a medical doctor has signed-off on the blood screening. A 6-week blood draw
will be taken to confirm that kidney and liver variables have not changed. Additional blood draws may be
obtained per physician discretion.
Body Composition: Height, weight will be recorded. Percent body-fat, fat-free mass, total and regional
adipose tissue mass, and total bone mineral density will be determined using whole-body dual energy x-
ray absorptiometry (DEXA) as we have previously used.
VO2Max: Subjects will undergo a 12-lead electrocardiogram (ECG) examination at rest and during a
graded exercise test on a stationary bicycle until volitional fatigue, in order to determine maximal oxygen
uptake (VO2max). ECG measurements will be made continuously, and blood pressure and ratings of
perceived exertion will be recorded. These tests will be performed in the Human Performance/Clinical
Research Laboratory (HPCRL) following standard procedures.
Skeletal Muscle Biopsy: Skeletal muscle biopsies will be performed using well-established IRB approved
SOPs. The belly of the vastus lateralis will be anesthetized locally with 1% lidocaine without epinephrine. A
small incision (~4-mm in length) will be made and a Bergstrom needle inserted. Negative pressure will be
applied to the inner channel of the needle using a sterile 30-ml plastic syringe. Benjamin Miller, Ph.D.,
Adam Konopka, Ph.D., or Matthew Hickey Ph.D. will perform the skeletal muscle biopsies. Collectively, the
investigative team has performed this procedure on over 1,000 subjects. A muscle sample will be obtained
once before and after the 12-week exercise training (a total of 2 muscle biopsies).
Exercise Training: The exercise-training program will be performed within the facilities for the Noon Hour
Fitness Program at CSU according to our previously published procedures in older individuals. Exercise
will be performed on a treadmill, stationary bicycle, or elliptical and include warm-up (15 min at a heart rate
corresponding to 60% of max ) and workout stages (30 min, progression from 65 to 85% of max heart rate
by wk 5). The participants will wear heart rate monitors to ensure proper heart rate ranges and the speed,
grade or resistance of equipment will be changed to maintain heart rate at the specified percentage of max
HR. A CPR trained technician will supervise each exercise session to monitor adherence to the exercise
prescription and ensure subject safety. The drinks will be consumed immediately after exercise under
supervision.
Nutritional Intervention: Subjects will consume either a protein-carbohydrate or carbohydrate drink with a
consistency and temperature similar to a smoothie or milk shake immediately after each exercise bout.
The protein-carbohydrate drink will be greek yogurt+fruit (~300 kcal, 63g carbohydrate, 20g protein, 1g fat)
and the carbohydrate will be fruit (~300 kcal, 82g carbohydrate, 2g protein and 1g fat).
Metformin and Placebo: We use a titration dosing protocol in which the amount of metformin starts at 500
mg/day in week 1 and increases by 500 mg/day/week until reaching 2000 mg/day by week 4. 2000 mg/day
is the standard clinical dose and used previously by the investigative team. The titration dosing scheme
and taking metformin/placebo with meals will help reduce the most common side effects (i.e.,
gastrointestinal discomfort). If participants experience gastrointestinal discomfort, the dose will be lowered
to 1500 mg/day. If participants have a body weight of 75 kg or less the maximal dose will be 1500 mg/day
to decrease the risk of gastrointestinal discomfort.
Stable Isotope Labeling: The subjects will consume D2O (70%; Cambridge Isotope Laboratories, Andover


Page 10 of 33
 
MA, USA) during the last four-week period of the 12 week intervention. D2O is a stable, non-radioactive
isotope that is indistinguishable from normal water,  A target of 1–2% enrichment is achieved during a one-
week priming stage (50 ml of D2O 3x/d = 150 ml/d) and maintained for three weeks (50 ml of D2O 2x/d =
100 ml/d) as we have previously performed.
Optional Continous Glucose Monitoring (CGM): CGM is a commonly used device to continuously measure
glucose values in healthy control and diabetic populations in both research and clinical applications. Only
trained members of the research team will place and remove the CGM devices following a standard
operating procedure and user guide.  The sensor pod will be secured to the skin of the abdomen using
medical grade adhesive. Once secure, a plunger will insert the sensor underneath the skin to record
interstitial glucose values every 5 minutes. After careful removal of the applicator, a transmitter will be
attached to the secured sensor pod. The transmitter sends data to a receiver. The receiver is smaller than
the size of a cell phone to easily fit in a pocket or bag. The receiver needs to be within 20 feet of the device
to continuously transmit data. The receiver will be set to blinded mode so the participant will not know their
glucose values. The device can be worn up to 10 days. After each 10-day wear a trained member of the
research team will remove the sensor. During the 10-day wear the device will  prompt the participant to
calibrate. After verbal and written instruction, participants will be shown how to perform a finger stick,
measure blood glucose using the glucose meter provided and enter the glucose value into the receiver to
calibrate the device. During the 10-day wear, participants will be provided a log to record the timing and
amount of medications, physical activity, food and drink.
Optional Physical Activity Behavior Counseling: After completion of the 12-week exercise intervention,
participants will be randomized to 1) receive one session of physical activity behavior counseling (PABC),
or 2) no counselling control (CON).The counseling session will consist of strategies based on social-
cognitive theory hypothesized to increase physical activity adherence. Session activities will include 1)
discussion of the benefits of physical activity, 2) discussion of evidence based recommendations for
frequency, intensity, time and type of physical activity for reducing the risk of type 2 diabetes and
associated co-morbidities, 3) setting individual physical activity goals, 4) identifying and discussing barriers
and facilitators for physical activity, and 5) identifying strategies to overcome barriers. The counseling
session will be completed in person while the follow-up questionnaires 12 weeks after completing the
exercise training can be done via phone or email.
Healthy participants will complete the medical history questionnaire, resting ECG, graded exercise testing
(ECG and VO2max), DEXA, OGTT, CGM, and muscle biopsy.
 
b)
Explain why human subjects must be used for this project.
We are interested in improving human health using recommendations by American Diabetes Association
with dairy protein supplementation and therefore need to use human subjects.
 
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.
No 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?
Clinical parameters obtained during the study will be available to the participants to share with their
primary physician. Then the subject and primary physician can decide on the most appropriate therapy for
the subject after the conclusion of the study.
 
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
differences are detected?
No alternative treatments
 
f)
State if deception will be used. If so, provide a rationale and describe debriefing procedures. Submit a


Page 11 of 33
 
debriefing script in the Attachment Section (#16).
No deception will be used.
 
3. Background
a)
Describe past experimental and/or clinical findings leading to the formulation of the study, if applicable.
Physical activity and the biguanide drug Metformin have been shown independently to reduce the
incidence of T2D. Interestingly, these data also suggest in adults over the age of 60 metformin had
marginal efficacy while physical activity lowered incidence of T2D by 70%. Currently, governing agencies
recommend physical activity and metformin together for individuals with pre-diabetes of all ages to prevent
the progression to overt T2D. Until recently, the interaction between exercise and metformin has been
largely understudied. Members of our investigative team have previously showed that metformin does not
enhance but may blunt the glucoregulatory and cardiovascular response to acute and chronic exercise,
which is especially relevant to older adults. A purported mechanism of action is that metformin inhibits
mitochondrial respiration, which likely limits VO2max and mitochondrial protein synthesis. We have
previously demonstrated that post-aerobic exercise dairy feeding can improve VO2max to a greater extent
than post-exercise carbohydrate beverage. Therefore, we feel dairy supplementation may override the
potential inhibition of metformin on exercise adaptations and maximize the benefits for older adults. To
date, real-time continuous glucose monitoring is limited in individuals at risk of T2D. Moreover, glucose
profiles via CGM during or in response to exercise, metformin and/or post-exercise nutrition have yet to be
fully characterized. Much clinical research is limited to measurements in the clinical research setting while
real-time glucose monitoring performed in both the standardized clinical research setting and in free-living
scenarios is novelty of the current study design that will close a gap in knowledge regarding
glucoregluatory effects of exercise, metformin and/or standardized post-exercise nutrition.
 
b)
Describe any animal experimentation and findings leading to the formulation of the study, if applicable.
---------------------------------------------------------------------------------------------
* * * 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) before and after
the 12 weeks of exercise in pre diabetic participants. In healthy individuals, one DEXA scan will be
performed.
  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
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.
 


Page 12 of 33
 
 
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.
Continous Glucose Monitor (CGM) described in study procedures and in the attached investigator
brochure and user guide. The Dexcom G6 CGM is for investigational use and is not FDA approved.
 
 
6. Investigational Devices
         Please list in the space below all Investigational Devices to be used on Subjects.
Investigational Devices
Investigational Devices
Describe the device(s) to be used
DEXCOM G6 Continuous Glucose Monitoring (CGM) System. CGM can supplement, but does not replace,
blood glucose monitoring. Previous versions of the device (Dexcom SEVEN PLUS, G4 PLATINUM, and G5
Mobile CGM) have been classified as a Class III device according to 21 CFR Part 814. The device’s
product code is MDS. Class III devices generally are those for which insufficient information exists to
determine that general or special controls are sufficient to provide a reasonable assurance of safety and
effectiveness.
Device Name
DEXCOM G6 Continuous Glucose Monitoring (CGM) System
Manufacturer
Dexcom, Inc.
Significant risk
Y
Non-Significant risk
IDE #
Rationale for Non-Significant Risk Device
Device is not exempt from requirements in 21 CFR 812. Device is intended as an implant? Device is
purported or represented to be for use supporting or sustaining human life? Device used of substantial
importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of
human health? Device presents a potential for serious risks to the health, safety, or welfare of a subject? If
yes to any, then considered SR device.
If a non-significant risk device study is indicated, provide rationale for the device being non-significant risk.
Please state if you need IRB guidance on whether this is a significant or non-significant risk device.
---------------------------------------------------------------------------------------------
* * * Drugs, Reagents, or Chemicals * * *
 


Page 13 of 33
 
 
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
Metformin
Source (e.g., Pharmacy, Sponsor, etc.,)
Pharmacy
If not premixed, where will the material be mixed and
by whom
Manufacturer
IND # (if available)
Dosage
Maximum dose of 1500 mg/day
Administration Route
Oral
N
 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) * * *
 
 
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).
We plan to recruit 120 men and women with an estimation that 15-25% of participants will not qualify (i.e.,
screen out) and 15-25% of participants will not complete the study (i.e. drop out). We plan to complete the
study in 60 men and women aged >55 years who are prediabetic defined as impaired fasting glucose (100
to 126 mg/dl), HbA1c (5.7-6.4%), family history of type 2 diabetes, and/or impaired glucose tolerance
defined as 2 hour postprandial blood glucose of 140 to 200 mg/dl. Participants will be eligible if they meet
any 1 of these criteria.
10 healthy individuals, 18-45 years old who have normal glucose values (fasting glucose (<100mg/dl),
HbA1c (<5.7%), 2 hour postprandial blood glucose (<140mg/dl)) or no family history of type 2 diabetes will
be recruited.
Sub-study: 20 pre diabetic participants and 10 healthy individuals will complete the study.
Subpopulation of [xx] participants will be recruited for Physical Activity Behavior Counseling (previously
approved in Amendment 3.
 
b)
What is the rationale for studying the requested group(s) of participants?


Page 14 of 33
 
Individuals at risk for T2D are the intended population for metformin; CGM; and Counseling studies. We
will use a healthy control group to compare to individuals at risk for T2D.
 
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.
We will not enroll minors, pregnant women, economically and educationally disadvantaged, or decisionally
impaired subjects.
 
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.
Minors are not included because the cost-benefit ratio is not clear and therefore inappropriate for this
study.
 
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
same written informed consent and compensation.
 
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.
Potential subjects will be recruited initially from the Colorado State and Fort Collins community via email,
electronic, newspaper, radio, or bulletin advertisements. Colorado State employees, local physicians and
interested participants may be emailed for recruitment and communication purposes. Physicians will be
contacted so if they have prediabetic patients they can be informed of the research study which includes
standard care treatment options (i.e., physical activity and metformin). Text for advertisements will be
obtained from the attached flyer. Information for local physicians is also attached.
 
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.
We will include healthy volunteers to compare to individuals at risk for T2D. No additional risks are known
for healthy individuals compared to those at risk for T2D. Healthy individuals will not perform the
intervention.
---------------------------------------------------------------------------------------------
* * * 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.
We plan to recruit 120 men and women with an estimation that 15-25% of participants will not
qualify (i.e., screen out) and 15-25% of participants will not complete the study (i.e. drop out).
We plan to complete the study in 60 men and women aged >55 years who are prediabetic
defined as impaired fasting glucose (100 to 126 mg/dl), HbA1c (5.7-6.4%), family history of type
2 diabetes, and/or impaired glucose tolerance defined as 2 hour postprandial blood glucose of
140 to 200 mg/dl. Participants will be eligible if they meet any 1 of these criteria.


Page 15 of 33
 
10 healthy participants will be recruited who are 18-45 years old who have normal glucose
values (fasting glucose <100mg/dl, HbA1c <5.7%, 2 hour postprandial blood glucose <140
mg/dl) and no family history of T2D.
 
 
  
   
Identify exclusion criteria.
Medications contraindicated with Metformin (Dofetilide, Lamotrigine, Pegvisomant, Somatropin,
Trimethoprim, Trospium, Gatifloxacin, Cephalexin, Cimetidine, Dalfampridine)
Recent (less than 6 weeks) or planned imaging that requires IV contrast
Renal failure, creatinine ≥ 1.3 mg/dL in men or ≥ 1.2 mg/dL in women
ALT levels exceed 52 IU/L
Heart, Kidney or Liver Disease
Type I or Type II Diabetes
Anti-coagulant therapy (warfarin/heparin)
Lung/respiratory dysfunction
Medications affecting primary outcomes
Lactose Intolerant
Tobacco Use
Heavy Alcohol Use
Cancer
Lidocaine Allergy
EKG that is nondiagnostic for ischemia, such as: Complete Left bundle branch block or
nonspecific Intraventricular conduction delay with ST/T changes; LVH with significant ST
changes; Wolff-Parkison-White syndrome;  ventricular pacemaker; digoxin therapy with greater
than 1 mm ST depression or
Arrythmias, such as: Uncontrolled rate in atrial fibrillation; nonsustained ventricular tachycardia.
 
i)
Describe your screening procedures. Attach your screening document(s) (e.g., health history
questionnaire) in the Attachment Section (#16).
Blood draw for chemistry panel, health questionnaire, medical history questionnaire, oral glucose tolerance
test, resting and exercise EC.
 
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 be instructed to communicate with investigators should they consider or begin to participate in
other studies. Subjects participating in studies that may confound the results of the present investigation
will be asked to withdraw from the the present investigation.
 
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).
Pre diabetic ubjects will be paid $500 at the completion of the study. Proration will occur at $20 per oral
glucose tolerance test and $50 per muscle biopsy. Participants that complete the CGM portion of this study
will receive additional compensation of $100 because of the additional time required for this study
component.
Healthy participants will be compensated $50 for the time spent completing the oral glucose tolerance test
(OGTT) and up to 10 days of CGM.
 
l)
Costs. Please explain any costs that will be charged to the subject.
Subjects will not incur any costs.
 
m)
Estimate the probable duration of the entire study. This estimate should include the total time each subject
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.
After initial screening Pre-diabetic subjects will undergo a 12 week intervention followed by post-
intervention assessments. Total time demand for each subject is estimated at 15 weeks with a total


Page 16 of 33
 
commitment of approximately 46 hours over that 15 weeks. If participants chose to participate in the
optional physical activity behavior counseling there will be additional time spent completing questionnaires
(less than 1 hr) at baseline, immediately after completion of exercise training and 12 weeks after
completion of exercise training but these can be completed via email or phone. Additionally, participants
will be randomized to complete 1 session of in person physical activity behavior counseling (approximately
1 hour).
Pre-diabetic subjects who choose to participant in wearing the Dexcom G6 CGM will wear it for up to 10
days at a time on three separate occasions: before, during and after the 12-week intervention.
Healthy subjects who participant in wearing the Dexcom G6 CGM will wear it for up to 10 days on one
occasion.
---------------------------------------------------------------------------------------------
* * * 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.
Dexcom CGM G6 is not an FDA approved device. This is currently available for research and
investigational purposes. Please see IB in attachments and notes in protocol notes. Wearing of
device should not be placed through baggage x-ray machine or body scanner. Rarely, the
sensor wire may break or detach from the sensor pod. These do not pose a significant medical
risk, but participants should contact the Study Coordinator within 24 hours if experiencing a
broken wire. Risks include infection, bleeding, pain or skin irritations (e.g., redness, swelling,
bruising, itching, scarring or skin discoloration) from the sensor and wearing the adhesive
patch.
 
 
   
   
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
 


Page 17 of 33
 
 
   
   
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.
Metformin has been commonly used as a diabetes medication for many years, both within and
outside of the US. It is safely used by nearly 50 Million people on a daily basis in the US.
Like most medication there are possible side effects: From the MAYO CLINIC:
Risks:
More common
Abdominal or stomach discomfort
Cough or hoarseness
Decreased appetite
Diarrhea
Fast or shallow breathing
Fever or chills
General feeling of discomfort
Lower back or side pain
Muscle pain or cramping
Painful or difficult urination
Sleepiness
Less common
Anxiety
Blurred vision
Chest discomfort
Cold sweats
Coma
Confusion
Cool, pale skin
Depression
Difficult or labored breathing
Dizziness
Fast, irregular, pounding, or racing heartbeat or pulse
Feeling of warmth
Headache
Increased hunger
Increased sweating
Nausea
Nervousness
Nightmares
Redness of the face, neck, arms, and occasionally, upper chest
Seizures
Shakiness
Shortness of breath
Slurred speech
Tightness in the chest
Unusual tiredness or weakness
Wheezing
Rare
Behavior change similar to being drunk
Difficulty with concentrating
Drowsiness
Lack or loss of strength
Restless sleep
Unusual sleepiness
 
 
   
   
4   
When performing procedures, please include all investigational, non-investigational and non-
invasive procedures (e.g., surgery, blood draws, treadmill tests).
Catheter Placement for OGTT (beginning and end of study): Minor discomfort of having the


Page 18 of 33
 
needle inserted and taped to an 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. This procedure is currently CSU-IRB
approved and active.
Muscle biopsy (beginning and end of study): The risk of allergic reaction to lidocaine and
lidocaine toxicity is extremely low (0 in the ~1500 cases witnessed by PI). There is a small risk
of infection at the site of incision. There is a small risk of the incision reopening/bleeding after
the subject leaves the lab. All subjects will have a small scar at the incision site. The rate and
degree of healing varies considerably, but it is expected that scars will be difficult to see within
6-12 months after the procedure.
Consumption of Heavy Water: Brief periods (< 30 minutes) of dizziness have been reported in a
small number of people (< 5%) after drinking special water. This is due to the special water
being heavier than normal water. Heavier water can temporarily disrupt your inner ear ability to
control balance, producing a sensation of dizziness.
Exercise and Exercise Testing (VO2max): 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 during
the graded exercise test can sometimes cause dryness in the mouth and mild discomfort.
CGM: The insertion of the CGM is a very quick procedure that causes no more discomfort than
the blood sampling or finger prick. The sensor sits beneath the skin and the participant should
not feel the senor once it is inserted. There is a small risk of infection, bleeding, pain or skin
irritations (e.g., redness, swelling, bruising, itching, scarring or skin discoloration) after inserting
the CGM sensor and wearing the adhesive patch. To minimize the risk of discomfort,
researchers will clean the area of skin with sterile alcohol swabs. The sensors and applicator
are shipped in sterile packaging and will be inserted within 5 minutes of opening package. Over
325 G6 CMG devices have been studied in 241 subjects across 9 independent clinical study
sessions. There were 5 total adverse events reported in these studies that included reddening,
irritation, infection and shooting pain at the site of the insertion or adhesive site that resolved
within 24 hours. No serious adverse device effects or unanticipated adverse device effects
were reported. A detailed report can be found in the investigational brochure in Section 4
Existing Clinical Data.
Fingersticks: Participants will likely experience brief (<30s) physical discomfort during the finger
stick procedure when the lancet goes into your finger. In about 10% of the cases a small
amount of bleeding under the skin will produce a bruise. A small scare may persist for several
weeks. The risk of local infection is less than 1 in 1,000 and is minimized by using the alcohol
(70% ethanol) swabs provided.
 
 
   
   
5  
Radioisotopes/radiation-producing machines(e.g., X-rays, CT scans, fluoroscopy).
Body Composition by DEXA scanning -
A small amount of radiation exposure (0.05 mRem) associated with the DEXA that is less than
1/20 of a typical chest x-ray. No immediate short-term or long-term risk to adults from this
radiation dose. This procedure is currently CSU-IRB approved and active.
 
 
c)      
For the following categories, include an estimate of the potential risk, if applicable.
 
 
   
   
1.   
Physical well-being.
None anticipated
 
 
   
   
2.   
Psychological well-being.
None anticipated


Page 19 of 33
 
 
 
   
   
3.   
Economic well-being.
None anticipated
 
 
   
   
4.   
Social well-being.
None anticipated
 
 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.
The potential risks of the proposed studies will be minimized by: a) using only safe, well-established
procedures; b) constant, personal monitoring of each experimental session by the investigators and their
respective staffs; and c) the availability of emergency equipment and medicine. Students and other
subordinate personnel on the research team will undergo the required human subjects training and will be
very carefully monitored in their technique and interactions with subjects.
Venous catheter risks
Venous catheters will only be placed by experienced phlebotomists.
Muscle Biopsy
The skin will be disinfected with Betadine and all instruments will be sterilized to reduce the risk of
infection.
Exercise
Qualified personel will supervise your initial resting and exercise ECG to determine if you are healthy
enough to perform regular exercise. During the exercise intervention a CPR trained exercise physiologist
will supervise every exercise session.
CGM
CGM will only be placed and removed by trained personnel following standard operating procedures. The
skin will be disinfected using sterile alcohol swabs.
 
 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.
---------------------------------------------------------------------------------------------


Page 20 of 33
 
* * * 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 pre diabetic and healthy individuals will learn about their physiology, body composition and general
cardiovascular risk factors determined from blood samples and ECG. Although there are no guaranteed
benefits from participating in this study, we are providing the first line of care for preventing the progression
of prediabetes to overt Type 2 Diabetes.  Therefore, the anticipated benefits of the research are a positive
effect on glucose metabolism, aerobic fitness, quality of life, and performance of daily activities.
 
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.
Research records and data will be stored on file in locked cabinets in the investigators' 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.
All data will be coded; e.g. XYZ123456
 
b)
If information derived from the study will be provided to the subject's personal physician, a government
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.
Information derived from this study will be available for the subjects to provide to their personal physician.
 
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 the investigators' 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.
All data will be coded; e.g. XYZ123456. De-identfied data from subjects who participate in the CGM
substudy will be shared with Dexcom, Inc.
---------------------------------------------------------------------------------------------
* * * 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?


Page 21 of 33
 
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. 
 
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
15-5837H CGM Consent 02242017
  Consent Information Type
Consent
  Sponsor's Consent Version Number: (if any)
Consent Form Template
X Attachment
 
15-5837 CGM Informed Consent
24Feb2017 (1)
<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?
  Title
15-5837H Main Study 24April2017 Stamped
  Consent Information Type
Consent
  Sponsor's Consent Version Number: (if any)
Consent Form Template
X Attachment
 
15-5837H Informed Consent
24April2017_Main Study RICRO
STAMPED (1)


Page 22 of 33
 
<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?
  Title
Healthy Individual Consent 11July2017
  Consent Information Type
Consent
  Sponsor's Consent Version Number: (if any)
Consent Form Template
X Attachment
 
15-5837 Informed Consent
Healthy Individuals (1)
<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?
---------------------------------------------------------------------------------------------
* * * 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 23 of 33
 
* * * 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
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


Page 24 of 33
 
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
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
1 page summary for clinicians v. 14May2015
Document Name
1 page summary for clinicians v. 14May2015
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
Verbal Recruitment 14May2015
Document Name
Verbal Recruitment 14May2015
Document Type
Questionnaire/Survey
Attachment
medical questionaire
Document Name
medical questionaire
Document Type
SOP
Attachment
B-01-R1 Biopsy SOP
Document Name
B-01-R1 Biopsy SOP
Document Type
SOP
Attachment
B-02-R1 Biopsy Needle Cleaning
Document Name
B-02-R1 Biopsy Needle Cleaning
Document Type
SOP
Attachment
HP-05-R1 Reporting AEs SOP
Document Name
HP-05-R1 Reporting AEs SOP
Document Type
SOP
Attachment
D2O-01-R1 Prep and Dispensing SOP
Document Name
D2O-01-R1 Prep and Dispensing SOP
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
Dairy Metformin Ad
Document Name
Dairy Metformin Ad
Document Type
Letters of Agreement.Cooperation
Attachment
Physician Support Letter
Document Name
Physician Support Letter


Page 25 of 33
 
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
CTS_Materials_Ad Examples
Document Name
CTS_Materials_Ad Examples
Document Type
Questionnaire/Survey
Attachment
BARSE
Document Name
BARSE
Document Type
Questionnaire/Survey
Attachment
EXSE_Baseline
Document Name
EXSE_Baseline
Document Type
Questionnaire/Survey
Attachment
EXSE
Document Name
EXSE
Document Type
Questionnaire/Survey
Attachment
IPAQ_English_self-admin_short
Document Name
IPAQ_English_self-admin_short
Document Type
Questionnaire/Survey
Attachment
NEWS
Document Name
NEWS
Document Type
Questionnaire/Survey
Attachment
Socioeconomic questionnaire
Document Name
Socioeconomic questionnaire
Document Type
Questionnaire/Survey
Attachment
Planning, Self-Regulation and Expectancy
Document Name
Planning, Self-Regulation and Expectancy
Document Type
Other Protocol Material
Attachment
Report - Draft 4
Document Name
Report - Draft 4
Document Type
Questionnaire/Survey
Attachment
15-5837H  Medical Screening form 19Feb2016
Document Name
15-5837H  Medical Screening form 19Feb2016


Page 26 of 33
 
Document Type
Other Protocol Material
Attachment
AE DC464 GI
Document Name
AE DC464 GI
Document Type
Other Protocol Material
Attachment
AE SR312 GI
Document Name
AE SR312 GI
Document Type
Other Protocol Material
Attachment
AE TA334 GI
Document Name
AE TA334 GI
Document Type
Other Protocol Material
Attachment
AE TA334 pink colored urine
Document Name
AE TA334 pink colored urine
Document Type
IBC Approval Letter
Attachment
IBC approval
Document Name
IBC approval
Document Type
Other Protocol Material
Attachment
AE AC693 GI present prior to start of intervention
Document Name
AE AC693 GI present prior to start of intervention
Document Type
Investigator's Brochure
Attachment
G6 Investigator Brochure
Document Name
G6 Investigator Brochure
Document Type
Investigator's Brochure
Attachment
CONTOUREZ-User-Guide-ENGLISH
Document Name
CONTOUREZ-User-Guide-ENGLISH
Document Type
SOP
Attachment
CGM SOP 9.1.16
Document Name
CGM SOP 9.1.16
Document Type
Investigator's Brochure
Attachment
Microlet2
Document Name
Microlet2
Document Type
Investigator's Brochure


Page 27 of 33
 
Attachment
G6 Blinded US_Study Instructions_User Guide
Document Name
G6 Blinded US_Study Instructions_User Guide
Document Type
Questionnaire/Survey
Attachment
Participant_Pre Screening 01Sept2016 v.2
Document Name
Participant_Pre Screening 01Sept2016 v.2
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
Dairy-Metformin Advertisement Example
Document Name
Dairy-Metformin Advertisement Example
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
Participant Testimonial
Document Name
Participant Testimonial
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
new recruiment flyer 1
Document Name
new recruiment flyer 1
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
new recruiment flyer 2
Document Name
new recruiment flyer 2
Document Type
Recruitment Material (e.g., flyers, email text, verbal
scripts)
Attachment
VIDEO PRODUCTION OUTLINE
Document Name
VIDEO PRODUCTION OUTLINE
Document Type
Other Protocol Material
Attachment
GCP protocol v 1.0 7 Decmber2016 v1.0
Document Name
GCP protocol v 1.0 7 Decmber2016 v1.0
Document Type
Other Protocol Material
Attachment
DOA CGM 03Feb2017
Document Name
DOA CGM 03Feb2017
Document Type
Grant/Sub-Contract
Attachment
Colorado State University - CTSA IIIS-2016-039 (11-
01-2016) (003)


Page 28 of 33
 
Document Name
Colorado State University - CTSA IIIS-2016-039 (11-
01-2016) (003)
Document Type
Grant/Sub-Contract
Attachment
CSU Dexcom Proposal 8.4.16
Document Name
CSU Dexcom Proposal 8.4.16
Document Type
Other Protocol Material
Attachment
15.5837H NSR DETERMINATION 02242017
Document Name
15.5837H NSR DETERMINATION 02242017
Document Type
Other Protocol Material
Attachment
15.5837 SR-NSR determination
Document Name
15.5837 SR-NSR determination
Document Type
Other Protocol Material
Attachment
Adverse Event Log 21April2017
Document Name
Adverse Event Log 21April2017
Document Type
Other Protocol Material
Attachment
CGM Adverse Event Log 03Feb2017
Document Name
CGM Adverse Event Log 03Feb2017
Document Type
Other Protocol Material
Attachment
Protocol Deviation CGM applied twice for pre
measurements 04April2017 signed
Document Name
Protocol Deviation CGM applied twice for pre
measurements 04April2017 signed
Document Type
Other Protocol Material
Attachment
Protocol Deviation consent signed
04March2017signed
Document Name
Protocol Deviation consent signed
04March2017signed
Document Type
Other Protocol Material
Attachment
Adverse Event Log 01June2017
Document Name
Adverse Event Log 01June2017
Document Type
Other Protocol Material
Attachment
CGM Adverse Event Log 01June2017
Document Name
CGM Adverse Event Log 01June2017


Page 29 of 33
 
---------------------------------------------------------------------------------------------
* * * 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
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.
 
  
  
Dr. Karyn Hamilton
X
The Principal Investigator has read and agrees to abide by the above obligations.
---------------------------------------------------------------------------------------------
* * * Event History * * *
Event History
Date
Status
View Attachments
Letters
04/29/2015
NEW FORM CREATED
05/15/2015
NEW FORM SUBMITTED
Y
05/15/2015
NEW FORM PANEL
ASSIGNED


Page 30 of 33
 
05/15/2015
NEW FORM REVIEWER(S)
ASSIGNED
05/18/2015
NEW FORM REVIEWER(S)
ASSIGNED
07/01/2015
NEW FORM REVIEWER(S)
ASSIGNED
07/27/2015
NEW FORM REVIEWER(S)
ASSIGNED
08/13/2015
NEW FORM MOVED
08/13/2015
NEW FORM APPROVED
Y
Y
08/24/2015
AMENDMENT 1 FORM
CREATED
08/24/2015
AMENDMENT 1 FORM
SUBMITTED
Y
08/24/2015
AMENDMENT 1 FORM
SUBMITTED
Y
08/25/2015
AMENDMENT 1 FORM
REVIEWER(S) ASSIGNED
10/07/2015
AMENDMENT 1 FORM
MOVED
10/07/2015
AMENDMENT 1 FORM
APPROVED
Y
Y
10/27/2015
AMENDMENT 2 FORM
CREATED
10/27/2015
AMENDMENT 2 FORM
SUBMITTED
Y
11/04/2015
AMENDMENT 2 FORM
REVIEWER(S) ASSIGNED
12/03/2015
AMENDMENT 2 FORM
APPROVED
Y
Y
12/03/2015
AMENDMENT 2 FORM UNDO
APPROVED
12/03/2015
AMENDMENT 2 FORM
MOVED
12/03/2015
AMENDMENT 2 FORM
APPROVED
Y
Y
12/14/2015
AMENDMENT 3 FORM
CREATED
12/14/2015
AMENDMENT 3 FORM
SUBMITTED
Y
12/15/2015
AMENDMENT 3 FORM
REVIEWER(S) ASSIGNED
01/06/2016
AMENDMENT 3 FORM
REVIEWER(S) ASSIGNED
01/21/2016
AMENDMENT 3 FORM
MOVED
01/21/2016
AMENDMENT 3 FORM
APPROVED
Y
Y
02/19/2016
AMENDMENT 4 FORM
CREATED
02/19/2016
AMENDMENT 4 FORM
SUBMITTED
Y
02/22/2016
AMENDMENT 4 FORM
REVIEWER(S) ASSIGNED
03/09/2016
AMENDMENT 4 FORM
REVIEWER(S) ASSIGNED


Page 31 of 33
 
03/16/2016
DEVIATION 1 FORM
CREATED
03/16/2016
DEVIATION 1 FORM
SUBMITTED
Y
03/17/2016
DEVIATION 2 FORM
CREATED
03/17/2016
DEVIATION 2 FORM
SUBMITTED
Y
03/18/2016
DEVIATION 2 FORM
REVIEWER(S) ASSIGNED
03/18/2016
DEVIATION 2 FORM
REVIEWER(S) ASSIGNED
03/18/2016
AMENDMENT 4 FORM
REVIEWER(S) ASSIGNED
03/21/2016
AMENDMENT 4 FORM
MOVED
03/21/2016
AMENDMENT 4 FORM
APPROVED
Y
Y
04/15/2016
DEVIATION 2 FORM
REVIEWER(S) ASSIGNED
04/15/2016
DEVIATION 1 FORM
REVIEWER(S) ASSIGNED
04/20/2016
CONTINUING REVIEW 1
FORM CREATED
04/27/2016
CONTINUING REVIEW 1
FORM SUBMITTED
Y
05/13/2016
CONTINUING REVIEW 1
FORM REVIEWER(S)
ASSIGNED
05/17/2016
DEVIATION 1 FORM
APPROVED
Y
N
05/17/2016
DEVIATION 2 FORM
APPROVED
Y
N
06/03/2016
CONTINUING REVIEW 1
FORM APPROVED
Y
Y
07/08/2016
REPORT 1 FORM CREATED
07/11/2016
REPORT 1 FORM
SUBMITTED
Y
07/18/2016
REPORT 1 FORM
REVIEWER(S) ASSIGNED
07/18/2016
REPORT 1 FORM
REVIEWER(S) ASSIGNED
08/10/2016
REPORT 1 FORM
APPROVED
Y
N
09/01/2016
AMENDMENT 5 FORM
CREATED
09/02/2016
AMENDMENT 5 FORM
SUBMITTED
Y
09/09/2016
AMENDMENT 5 FORM
REVIEWER(S) ASSIGNED
09/12/2016
AMENDMENT 5 FORM
REVIEWER(S) ASSIGNED
10/10/2016
AMENDMENT 5 FORM
REVIEWER(S) ASSIGNED
10/13/2016
REPORT 2 FORM CREATED


Page 32 of 33
 
10/14/2016
REPORT 2 FORM
SUBMITTED
Y
10/14/2016
REPORT 2 FORM
REVIEWER(S) ASSIGNED
11/02/2016
AMENDMENT 5 FORM
MOVED
11/02/2016
AMENDMENT 5 FORM
APPROVED
Y
Y
11/02/2016
AMENDMENT 5 FORM UNDO
APPROVED
11/02/2016
AMENDMENT 5 FORM
APPROVED
Y
Y
11/30/2016
AMENDMENT 6 FORM
CREATED
11/30/2016
AMENDMENT 6 FORM
SUBMITTED
Y
12/07/2016
AMENDMENT 6 FORM
REVIEWER(S) ASSIGNED
12/14/2016
AMENDMENT 6 FORM
MOVED
12/14/2016
AMENDMENT 6 FORM
APPROVED
Y
Y
01/05/2017
DEVIATION 3 FORM
CREATED
01/05/2017
DEVIATION 3 FORM
SUBMITTED
Y
01/06/2017
DEVIATION 3 FORM
REVIEWER(S) ASSIGNED
01/07/2017
REPORT 2 FORM
APPROVED
Y
N
01/11/2017
DEVIATION 3 FORM
REVIEWER(S) ASSIGNED
02/02/2017
AMENDMENT 7 FORM
CREATED
02/03/2017
AMENDMENT 7 FORM
SUBMITTED
Y
02/10/2017
AMENDMENT 7 FORM
REVIEWER(S) ASSIGNED
02/13/2017
DEVIATION 4 FORM
CREATED
02/13/2017
DEVIATION 4 FORM
SUBMITTED
Y
02/22/2017
AMENDMENT 7 FORM
REVIEWER(S) ASSIGNED
02/22/2017
AMENDMENT 7 FORM
REVIEWER(S) ASSIGNED
02/24/2017
AMENDMENT 7 FORM
REVIEWER(S) ASSIGNED
02/27/2017
AMENDMENT 7 FORM
MOVED
02/27/2017
AMENDMENT 7 FORM
APPROVED
Y
Y
03/23/2017
AMENDMENT 8 FORM
CREATED
04/24/2017
AMENDMENT 8 FORM
SUBMITTED
Y


Page 33 of 33
 
04/25/2017
AMENDMENT 8 FORM
REVIEWER(S) ASSIGNED
04/26/2017
AMENDMENT 8 FORM
APPROVED
Y
Y
05/04/2017
CONTINUING REVIEW 2
FORM CREATED
05/04/2017
CONTINUING REVIEW 2
FORM SUBMITTED
Y
05/12/2017
CONTINUING REVIEW 2
FORM REVIEWER(S)
ASSIGNED
05/19/2017
CONTINUING REVIEW 2
FORM APPROVED
Y
Y
05/25/2017
DEVIATION 3 FORM
APPROVED
Y
N
07/05/2017
AMENDMENT 9 FORM
CREATED
07/11/2017
AMENDMENT 9 FORM
SUBMITTED
Y
07/14/2017
AMENDMENT 9 FORM
REVIEWER(S) ASSIGNED
07/18/2017
DEVIATION 4 FORM MOVED
07/18/2017
DEVIATION 4 FORM
APPROVED
Y
N
07/24/2017
AMENDMENT 9 FORM
REVIEWER(S) ASSIGNED
07/27/2017
DEVIATION 5 FORM
CREATED
07/27/2017
AMENDMENT 9 FORM
APPROVED
Y
Y
07/27/2017
AMENDMENT 9 FORM UNDO
APPROVED
07/27/2017
AMENDMENT 9 FORM
APPROVED
Y
Y
07/27/2017
DEVIATION 5 FORM
SUBMITTED
Y
08/09/2017
DEVIATION 5 FORM
REVIEWER(S) ASSIGNED
08/28/2017
DEVIATION 5 FORM
APPROVED
Y
N
04/04/2018
CONTINUING REVIEW 3
FORM CREATED
05/09/2018
CONTINUING REVIEW 3
FORM SUBMITTED
Y
05/15/2018
CONTINUING REVIEW 3
FORM MOVED
05/15/2018
CONTINUING REVIEW 3
FORM APPROVED
Y
Y
10/03/2018
AMENDMENT 10 FORM
CREATED
10/04/2018
AMENDMENT 10 FORM
SUBMITTED
Y
10/04/2018
AMENDMENT 10 FORM
APPROVED
Y
Y


Statistical Plan  
Data are presented as mean ± standard error of the mean (SEM) and a significance 
was set a priori at P<0.05. Normality was confirmed by the D’Agostino and Pearson 
test. A two-way ANOVA (Treatment Group x Time) with repeated measures for time 
was performed. Upon a significant effect, a Holm-Sidak’s post-hoc test was used for 
multiple comparisons. When comparing the change (∆) from pre to post-intervention 
between groups, data were analyzed using an unpaired t-test. Pearson’s correlation 
coefficient (r) was used to determine associations between dependent variables. 
GraphPad Prism 7.0 was used to perform statistical analysis 

ICF_001.pdf: 
Colorado State University 
Human Performance Research Laboratory 
Protocol: 15-5837H 
Fort Collins, CO                      Principal Investigators: Drs. B. Miller and K. Hamilton           Study Contact: Adam Konopka 
Informed Consent:  
(970)491-3291 
(970)491-7193 
 
Page 1 of 7 Participant’s initials _______ Date _______  
v. 24April2017 
CSU#: 15-5837H 
APPROVED: 5/20/2017 *EXPIRES: 5/19/2018 
Consent to Participate in a Research Study 
Colorado State University 
 
TITLE OF STUDY: Milk protein feeding after aerobic exercise in older adults with 
pre-diabetes taking the biguanide Metformin 
 
PRINCIPAL INVESTIGATOR: Benjamin F. Miller PhD, Associate Professor, Department of Health and 
Exercise Science, Colorado State University. Benjamin.f.miller@colostate.edu, (970) 491-3291, and Karyn 
Hamilton, Associate Professor, Department of Health and Exercise Science, Colorado State University, 
Karyn.Hamilton@colostate.edu.   
 
WHY AM I BEING INVITED TO TAKE PART IN THIS RESEARCH?   
If you are over the age of 55 and have fasting glucose values ≥100 mg/dl, hemoglobin A1c ≥5.7 to <6.4%,  
impaired glucose tolerance (glucose 2 hours postprandial ≥140 to <200 mg/dl), or a family history of type 2 
diabetes then we are interested in you taking part in this study. Males and females are invited to participate.  
Sixty participants will be selected to participate in this study.  
 
WHO IS DOING THE STUDY?  Drs. Miller and Hamilton are Associate Professors in the Department of 
Health and Exercise Science at CSU and are interested in using exercise and nutrition to combat the risk of 
developing Type 2 Diabetes with increasing age. Drs. Miller and Hamilton will be assisted by Post-doctoral 
researcher Dr. Adam Konopka and graduate students of the laboratory. 
 
WHAT IS THE PURPOSE OF THIS STUDY?   
As people age, they are at an increased risk of developing Type 2 Diabetes.  The anti-diabetic drug Metformin 
and exercise are the standard treatments to prevent Type 2 Diabetes although there is evidence that 
Metformin may inhibit some of the positive effects of exercise. We are interested in testing how protein from 
dairy products could help restore the beneficial effect of exercise when taking Metformin. 
 
WHERE IS THE STUDY GOING TO TAKE PLACE AND HOW LONG WILL IT LAST? 
The study will take place in the Department of Health and Exercise Science at Colorado State University 
and will last three years. Total time demand for each subject is estimated at 15 weeks that includes a 12-
week, supervised exercise program and dietary intervention.   
 
WHAT WILL I BE ASKED TO DO?  
The time commitment in full is explained below for each group followed by detailed procedures.   
 
You will be expected to: 
• 
Participate in an initial screening procedure that includes detailed review of the informed consent, 
physical activity and medical history questionnaire (approximately 45 min).  
• 
Complete an oral glucose tolerance test (approximately 2 hrs). 
• 
Perform an ECG during resting and exercise conditions (approximately 1 hr).  
• 
Measure body weight and composition via a dual x-ray absorptiometry (DEXA) scan, followed by 
providing a muscle sample (once before and once after the intervention) for a total of two muscle 
samples for the entire study (approximately 1 hr). 
• 
Consume labeled water during the last 4 weeks of the study (1 minute daily). 
• 
Participate in a 12-week exercise intervention (approximately 45 min/day, 3 days/week). 
• 
Consume a nutritional beverage (i.e, a smoothie) immediately after each exercise bout (<15 minutes). 
• 
Optionally complete questionnaires to measure sociodemographic information, physical activity, self-
efficacy, planning, self-regulation and outcome expectancy of exercise, and perceptions of 
neighborhood support for physical activity and participate in physical activity behavior counseling (<1 
hour) 
• 
After the 12-week exercise intervention, repeat the oral glucose tolerance test (2 hrs), DEXA scan, 
body weight measurement and an exercise ECG (approximately 1 hour) as well as complete the 
questionnaires and physical activity behavior counseling, if applicable.  


Colorado State University 
Human Performance Research Laboratory 
Protocol: 15-5837H 
Fort Collins, CO                      Principal Investigators: Drs. B. Miller and K. Hamilton           Study Contact: Adam Konopka 
Informed Consent:  
(970)491-3291 
(970)491-7193 
 
Page 2 of 7 Participant’s initials _______ Date _______  
v. 24April2017 
CSU#: 15-5837H 
APPROVED: 5/20/2017 *EXPIRES: 5/19/2018 
 
Before undergoing the sampling procedures, you will be asked a few questions related to your past and 
present state of health, current medication and past medical history.  This is to exclude the presence of any 
condition or medication that might prolong your bleeding time, make blood sampling unsafe for you or be 
contraindicated with exercise or the drug Metformin. Following this examination, 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 over 
2 hours.  In total, we will sample a small amount of blood (~ 100 ml or 7 tablespoons per test). The first 
sample will be used to inform us if your liver and kidneys are healthy. In addition, the first and subsequent 
samples will be used to determine how your body regulates blood glucose after an overnight fast and after 
consuming a sugary drink. This test is called an oral glucose tolerance test and is commonly done in 
research and medical settings. A small blood sample will also be taken after week 6 to monitor liver and 
kidney enzymes after six weeks of metformin and/or exercise. 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. 
 
If you meet the study criteria, you will also undergo cardiac screening in the presence of qualified personnel.  
This will involve the placement of 12 electrodes on your chest, which will be connected to an 
electrocardiogram (ECG). This will be done at rest and during a graded exercise test (stress test) performed 
on a stationary bicycle. A mouthpiece will also be used to collect the gas you are breathing during exercise. 
This test will measure your fitness levels and indicate whether you can safely perform the exercise 
intervention. 
 
If anything adverse is found in any of the medical screening, you will be notified. A copy of your results will 
be available for you.  You may wish to speak with your primary care physician to have the results explained 
to you.  We will not share any information that may be used to identify you. 
 
In the next visit, we will measure your body weight, height, and body composition by DEXA. Subsequently, a 
small (100-200mg, about the size of a pea) sample of muscle will be taken from one of your thighs.  This will 
be done under a local anesthetic.  A small (6-8mm or approximately 1/3 of an inch) cut will be made in your 
skin and another cut of the same size in your muscle.  The muscle sample will be taken under sterile 
conditions and will be carried out by an experienced investigator (Dr. Benjamin Miller PhD, Dr. Matthew 
Hickey PhD, or Dr. Adam Konopka PhD) with medical oversight.  Following this, pressure and ice will be 
applied, the incision will be secured by band-aids, then firmly bandaged with gauze. The biopsy procedure 
will not prevent you from performing any of your normal daily activities afterwards.  After 12 hours you can 
remove the gauze, by three or four days the steri-strips will fall off, and the incision will heal normally like a 
cut. The resultant scar will gradually fade and be hardly noticeable.  This visit will last about an hour. 
 
You will be randomized to participate in 1 of 4 groups outlined in table 1 below. All groups will perform a 12-
week exercise intervention.  The exercise will be performed on a treadmill, stationary bicycle or elliptical for 
45 minutes, 3 days per week. For the first 15 minutes, the desired exercise intensity will be 60% of your heart 
rate max and the next 30 minutes will progressively increase from 65 to 85% of heart rate max on a weekly 
basis. A trained member of the investigative team will supervise all exercise sessions by watching a heart 
rate monitor that you will wear during the exercise session. Immediately following each exercise bout, you 
will be asked to consume a ~300 calorie smoothie beverage that contains either 20 grams of protein plus 
carbohydrate (yogurt and fruit) or carbohydrate (fruit) only, although you will be blinded to which treatment 
you are assigned to.   
 
In addition, you will be asked to consume capsule(s) consisting of either Metformin or placebo. During the 
first 4 weeks, the pill consumption is increased each week by 500 mg/day until a maximum dose of 2000 
mg/day is reached, which is the standard therapeutic dose (see table 2). For participants with a body weight 
of ≤75kg, the maximum dose will be 1500 mg/day to decrease the risk of side effects. Increasing the dose 
slowly and consuming Metformin with food helps avoid gastrointestinal side effects.  
 
 
 
Table 1. Outline of the four groups within this study.  


Colorado State University 
Human Performance Research Laboratory 
Protocol: 15-5837H 
Fort Collins, CO                      Principal Investigators: Drs. B. Miller and K. Hamilton           Study Contact: Adam Konopka 
Informed Consent:  
(970)491-3291 
(970)491-7193 
 
Page 3 of 7 Participant’s initials _______ Date _______  
v. 24April2017 
CSU#: 15-5837H 
APPROVED: 5/20/2017 *EXPIRES: 5/19/2018 
Group 
Exercise 
Nutrition 
Drug 
Group 1 
12-wks Exercise 
Carbohydrate 
Placebo 
Group 2 
12-wks Exercise 
Protein 
Placebo 
Group 3 
12-wks Exercise 
Carbohydrate 
Metformin 
Group 4 
12-wks Exercise 
Protein 
Metformin 
 
 
Table 2. Dosing scheme for both metformin and placebo 
Week 
Daily Dose (mg) 
Number of Pills With Meal 
Week 1 
500 
1 pill with dinner 
Week 2 
1000 
1 pill with breakfast and 1 pill with dinner 
Week 3 
1500 
1 pill with breakfast and 2 pills with dinner 
Week 4-12 
2000 
2 pills with breakfast and 2 pills with dinner 
 
During the last 4 weeks of this 12-week exercise and nutritional intervention you will be asked to drink a small 
volume of labeled water daily. During study week 9, you will consume a small cup of water (50 ml) three times 
a week, and during weeks 10-12 you will consume a small cup of water (50 ml) twice a day. The glass of 
water you will consume contains what is called an isotope of water. The water we provide you has a label 
that makes the water heavier, but imperceptible to you.  This label is present naturally, but we add it in a 
higher concentration in order to follow metabolic reactions in the body.  You will not notice this label, nor will 
it change anything in your body.  We can only locate it by special analysis procedures after sample collection.    
 
You will be asked to recall and record your food intake from the day before your first glucose tolerance test 
and then repeat the same food intake the day before your second glucose tolerance test.  
 
A second graded exercise test as well as a DEXA scan will be completed to measure any change in fitness 
and body composition, respectively.  
 
Two to three days after the last exercise session, you will repeat the muscle biopsy procedure in which a 
small piece of muscle will be obtained from one of your thighs. 
 
Participants will be given the option to participate in an additional study component to determine the impact 
of physical activity behavior counseling following exercise training on levels of physical activity 12 weeks after 
the intervention ends as well as identifying individual, socio-cultural and environmental determinants of 
physical activity three months after the end of the exercise intervention.  
 
If subjects decide to participate, after completion of the 12-week exercise intervention, participants will be 
randomized to 1) receive one session of physical activity behavior counseling (PABC), or 2) no counseling 
control (CON). The counseling session will consist of strategies based on social-cognitive theory. Session 
activities will include 1) discussion of the benefits of physical activity, 2) discussion of evidence based 
recommendations for frequency, intensity, time and type of physical activity for reducing the risk of type 2 
diabetes and associated co-morbidities, 3) setting individual physical activity goals, 4) identifying and 
discussing barriers and facilitators for physical activity, and 5) identifying strategies to overcome barriers.  
 
Table 3 Timeline of Questionnaires and Counseling Session 
 
Baseline 
Post 
Intervention 
Post Behavior 
Counseling Session 
3 Month Follow-
Up 
Sociodemographics 
X 
 
 
 
Physical Activity (IPAQ) 
X 
X 
 
X 
Self-Efficacy (EXSE & BARSE) 
X 
X 
X 
X 
Planning, Self-Regulation, and  
Expectancy 
X 
X 
X 
X 
Neighborhood Support (NEWS) 
X 
 
 
 
ARE THERE REASONS WHY I SHOULD NOT TAKE PART IN THIS STUDY? 


Colorado State University 
Human Performance Research Laboratory 
Protocol: 15-5837H 
Fort Collins, CO                      Principal Investigators: Drs. B. Miller and K. Hamilton           Study Contact: Adam Konopka 
Informed Consent:  
(970)491-3291 
(970)491-7193 
 
Page 4 of 7 Participant’s initials _______ Date _______  
v. 24April2017 
CSU#: 15-5837H 
APPROVED: 5/20/2017 *EXPIRES: 5/19/2018 
• 
You should not participate if you have or have had any problems with bleeding, lung, kidney or liver 
dysfunction, heart failure, Type 1 or overt Type 2 diabetes, be on medication that prolongs bleeding 
time, or medications known to alter metabolism.  
• 
You should not participate if you have had or are planning to have imaging that requires intravenous 
contrast dye (within 6 weeks) or are on any of the following medications since they are 
contraindicated with the use of Metformin: Dofetilide, Lamotrigine, Pegvisomant, Somatropin, 
Trimethoprim, Trospium, Gatifloxacin, Cephalexin, Cimetidine, Dalfampridine.  
• 
You should not participate if you have cancer or are in remission for < 5 years. 
• 
Because tobacco is known to affect the factors being investigated, you cannot participate if you use 
tobacco.   
• 
If you are allergic to dairy products (lactose intolerant), lidocaine, or Metformin you should not 
participate because these items will be administered during this study.  
 
Any change in medication (prescription or over the counter) during the study needs to be immediately reported 
to the study team to ensure your safety.   
 
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS?  
These procedures are all low risk in a healthy population.   
• 
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 during the graded exercise test can sometimes cause dryness in the mouth 
and mild discomfort. 
• 
You are likely to experience temporary physical discomfort during the blood sampling procedure, the 
possibility of bruising or fainting, and an extremely slight risk of infection.  Discomfort during the blood 
sampling is minor and brief (<30s) and bruising will not last more than one week.   
• 
There is a small risk of infection at the site of the incision for the muscle biopsy, and a small risk of 
the biopsy incision reopening or bleeding after you leave the lab.  The risk of allergic reaction to 
lidocaine (the anaesthetic used for the biopsy incision) is extremely low.  There is also a risk of fainting 
or muscle cramp during the procedure, loss of feeling in the leg, damage to the skin (cutaneous) 
nerve and a risk of bruising around the biopsy site. You will have a small scar at the incision site.  
The rate and degree of healing varies considerably, but it is expected that scars will be difficult to see 
within 6-12 months after the procedure. 
• 
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. 
• 
In a small number of cases, transient dizziness may result from the initial consumption of the heavy 
water.   
• 
Metformin has the risk of causing several side effects, however, there are nearly 50 Million people 
in the US who use metformin on a daily basis to treat their diabetes and do not experience any side 
effects from Metformin use. You should be aware that metformin may cause lactic acidosis (a build-
up of lactic acid in the body, that may be fatal). Lactic acidosis can start slowly and get worse over 
time and is more prevalent in those with liver or kidney disease or heart failure. Contact the study 
team and/or seek medical attention immediately if you have even mild symptoms of lactic acidosis, 
such as: muscle pain or weakness; numb or cold feeling in your arms and legs; trouble breathing; 
feeling dizzy, light-headed, tired, or very weak; stomach pain, nausea with vomiting; or slow or 
uneven heart rate. Call 911 or your doctor at once if you have any other serious side effects such 
as: feeling short of breath, even with mild exertion; swelling or rapid weight gain; or fever, chills, 
body aches, flu symptoms. Less serious side effects of metformin may include: headache or muscle 
pain; weakness; or mild nausea, vomiting, diarrhea, gas, stomach pain. It is important to stay 


Colorado State University 
Human Performance Research Laboratory 
Protocol: 15-5837H 
Fort Collins, CO                      Principal Investigators: Drs. B. Miller and K. Hamilton           Study Contact: Adam Konopka 
Informed Consent:  
(970)491-3291 
(970)491-7193 
 
Page 5 of 7 Participant’s initials _______ Date _______  
v. 24April2017 
CSU#: 15-5837H 
APPROVED: 5/20/2017 *EXPIRES: 5/19/2018 
hydrated (drink lots of water) while taking metformin. This is not a complete list of side effects and 
others may occur. Although very rare metformin may cause low blood sugar which could be masked 
if you are taking beta-blockers to control blood pressure. Call your doctor or ask the researchers for 
advice about side effects. In the US, Metformin is also known as Fortamet / Glucophage / 
Glucophage XR / Glumetza / and, Riomet.  
 
• 
Here is a list of possible side effects of Metformin collated into most likely, less likely, rarely, and 
rare but serious. 
 
• 
Most Likely (greater than 20%): These symptoms are generally temporary, occur during the start 
of treatment, and disappear without stopping the drug.  
• Diarrhea 
• Nausea 
• Vomiting 
• Abdominal bloating 
• Flatulence (gas) 
• Anorexia (loss of appetite) 
 
• 
Less likely [Occasional] (5 to 20%): 
• 
Loss of taste or metallic taste (during start of therapy) 
• 
Minor weight loss (less than 1 kilogram or 2 pounds) 
• 
Reduced appetite 
 
• 
Rarely (1 to 4%): These effects will disappear when Metformin is stopped. 
• 
Rash, redness or itchiness 
• 
Decrease in the level of a vitamin in the blood (called B12) that does not cause symptoms  
• 
Decrease in the red blood cell count  
• 
Liver function test abnormalities as seen by blood tests or hepatitis (inflammation of the liver) 
• 
Anxiety and nervousness 
• 
Depression 
 
• 
Rare but Serious (less than 1%): 
• 
Lactic acidosis (a high acid level in the blood) occurs rarely (3 cases per 100,000 years of 
use) and can cause death. Individuals at risk of this complication include persons with 
diabetes who have kidney, liver or heart abnormalities. Symptoms of lactic acidosis may 
include tiredness, muscle aches, difficulty breathing, vomiting or severe abdominal pain.   
 
• 
There are reproductive risks, as well, so women of child bearing potential should not become 
pregnant and men should not father a child.  
 
• 
There are alcohol consumption risks: Participants should not drink excessive alcohol while taking 
the drug. There is a limit of less than 3 alcoholic beverages/day. 
 
• 
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. 
 
You may contact the investigators before and after working hours if you have medical concerns 
pertaining to study participation. Please first contact Adam Konopka at 507-602-2322 then if unable 
to reach Adam, please contact Benjamin Miller at 970-217-7906.  
 
ARE THERE ANY BENEFITS FROM TAKING PART IN THIS STUDY?   
Although there are no guaranteed benefits from participating in this study. Current clinical practice includes 
lifestyle modifications with or without the use of Metformin as the first line of care for preventing the 
progression to overt Type 2 Diabetes. 
 
DO I HAVE TO TAKE PART IN THE STUDY?   


Colorado State University 
Human Performance Research Laboratory 
Protocol: 15-5837H 
Fort Collins, CO                      Principal Investigators: Drs. B. Miller and K. Hamilton           Study Contact: Adam Konopka 
Informed Consent:  
(970)491-3291 
(970)491-7193 
 
Page 6 of 7 Participant’s initials _______ Date _______  
v. 24April2017 
CSU#: 15-5837H 
APPROVED: 5/20/2017 *EXPIRES: 5/19/2018 
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?   
It will not cost you any money to participate in the study.  Any treatment or medical costs that arise as a result 
of your participation in this study are your responsibility.  
 
WHO WILL SEE THE INFORMATION THAT I GIVE?    
We will keep private all research records that identify you, to the extent allowed by law. 
 
Your information will be combined with information from other people taking part in the study. 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.  
 
In the researchers’ records you will be identified by a number. We will make every effort to prevent anyone 
who is not on the research team from knowing that you gave us information, or what that information is.  For 
example, your name will be kept separate from your research records and these two things will be stored in 
different places under lock and key. Your identity/record of receiving compensation (NOT your data) may be 
made available to CSU officials for financial audits. We may be asked to share the research files for audit 
purposes with the CSU Institutional Review Board ethics committee, if necessary, and the Food and Drug 
Administration (FDA). 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.  
A description of this clinical trial will be available on http://www.ClincialTrials.gov, as required by U.S. Law.  
This website will not include information that can identify you.  At most, the website will include a summary of 
the results.  You can search this website at any time. 
 
CAN MY TAKING PART IN THE STUDY END EARLY?   
If you are not compliant with any aspect of the intervention, including the exercise training, or if you miss too 
many appointments, you will be removed from the study.   
 
WILL I RECEIVE ANY COMPENSATION FOR TAKING PART IN THIS STUDY?   
You will receive free heart screening, stress test, comprehensive blood panel, oral glucose tolerance test and 
DEXA scan.  At the completion of the study you will receive $500 for your participation.  If you do not complete 
the study, you will be compensated $20 for each oral glucose tolerance test completed and $50 for each 
muscle sample obtained.  
 
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.  However, you 
or your insurance company will have to pay for that care. The Colorado Governmental Immunity Act 
determines and may limit Colorado State University's legal responsibility if an injury happens because of 
this study. Claims against the University must be filed within 180 days of the injury. 
 
WHAT IF I HAVE QUESTIONS?       
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 our laboratory at 970-
491-7913, Dr. Adam Konopka at 970-491-7193 or Dr. Benjamin Miller at 970-491-3291. 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. 
 
 
 
 


Colorado State University 
Human Performance Research Laboratory 
Protocol: 15-5837H 
Fort Collins, CO                      Principal Investigators: Drs. B. Miller and K. Hamilton           Study Contact: Adam Konopka 
Informed Consent:  
(970)491-3291 
(970)491-7193 
 
Page 7 of 7 Participant’s initials _______ Date _______  
v. 24April2017 
CSU#: 15-5837H 
APPROVED: 5/20/2017 *EXPIRES: 5/19/2018 
If you are interested in participating in the additional study component please check the box below. You may 
still participate in this study if you do not wish to complete this additional study component.  
 
 Wear a continuous glucose monitor (CGM) for 10 consecutive days at three different time points 
(before, during, and after intervention for a total of 30 days) to measure and record your glucose values  
every 5 minutes during those 10 day blocks of time.  
 
 Complete questionnaires to measure sociodemographic information, physical activity, self-efficacy, 
planning, self-regulation and outcome expectancy of exercise, and perceptions of neighborhood 
support for physical activity and participate in physical activity behavior counseling. 
  
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 7 pages.  
 
_________________________________________  
_____________________ 
Signature of person agreeing to take part in the study 
 
 
Date 
 
_________________________________________ 
Printed name of person agreeing to take part in the study 
 
_______________________________________ 
 
_____________________ 
Name of person providing information to participant  
 
 
Date 
 
_________________________________________    
Signature of Research Staff