Conditions: Diabetes Pre-Diabetes
Keywords: Pre-Diabetes cinnamon
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 229
Healthy volunteers: no

Brief summary:
The purpose of this study is to assess whether water-soluble cinnamon extract plus aggressive lifestyle intervention is effective in lowering blood glucose in pre-diabetic patients when compared to aggressive lifestyle therapy plus placebo.

Detailed description:
We are studying whether water-soluble cinnamon extract (Cinnulin PF) plus standard of care aggressive lifestyle therapy is effective in lowering blood glucose when compared to placebo plus standard of care aggressive life style therapy. Eligible subjects will be recruited from any form and any stage of "standard" lifestyle intervention for pre-diabetes at an individual base. "Standard" lifestyle intervention for pre-diabetes could include Group Lifestyle Balance (GLB), nutrition classes, Better Body/Better Life, or anything an investigator certifies as standard practice at that base. Subjects will take either 1 gram (2-500 milligram (mg) capsules) of water-soluble cinnamon extract (Cinnulin PF) or 2 placebo pills (gelatin capsule filled with wheat bran) once a day for 1 year plus 1 additional year of follow-up. This is a randomized, double-blind, multicenter, placebo-controlled study which will enroll subjects at the Mike O'Callaghan Federal Medical Center (MOFMC), Wilford Hall Ambulatory Surgical Center (WHASC), David Grant Medical Center (DGMC), Eglin Air Force Base (Eglin), and Offutt Air Force Base (Offutt). All subjects will be MOFMC, WHASC, DGMC, Eglin, and Offutt DoD beneficiaries. Informed Consent and HIPAA Authorization will be obtained. After randomization, subjects will receive either 1 gram (2-500 mg capsules) of water-soluble cinnamon extract or placebo from the pharmacy--thus investigators and subjects will be blinded as to if they are taking Cinnulin PF or 2 placebo pills. Subjects will be permitted to have usual medical care for other co-morbid, preventive, and acute conditions. Analysis will be performed using intention-to-treat principles for missing data (the carry-forward method to impute missing data will be used). Subjects will bring in any remaining water-soluble cinnamon extract or placebo to determine adherence rates to the study protocol.

Arms:
arm 1: Will take (by mouth) 2 gelatin capsules that contains 1 gram (2-500 mg capsules) water-soluble cinnamon extract (Cinnulin PF) once a day for 1 year plus 1 year of follow-up plus standard of care aggressive lifestyle therapy. arm 2: Will take (by mouth) 2 placebo capsules (gelatin capsule filled with wheat bran) once a day for 1 year plus 1 year of follow-up plus standard of care aggressive lifestyle therapy.

Interventions: intervention 1: water-soluble cinnamon extract (Cinnulin PF)
Intervention descriptions: intervention 1: Will take (by mouth) 1 gelatin capsule that contains 1 gram water-soluble cinnamon extract (Cinnulin PF) once a day for 12 months plus standard of care aggressive lifestyle therapy

Protocol document:
Prot_SAP_000.pdf: 
Cinnamon Trial-lIfestyle iNtervention Plus Water-soluble Cinnamon 
Extract On loweriNg Blood Glucose in Pre-diabetics 
NCT01301521
 January 24, 2018


Revised by PR 2019
1
PROTOCOL FOR CLINICAL INVESTIGATION – NON-EXEMPT HUMAN
(Wilford Hall Ambulatory Surgical Center – WHASC)
PROTOCOL SUMMARY
1. Title:
Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg 
blood glucose in pre-diabetics: A randomized, double-blind, multicenter, placebo controlled TRIAL.
FWH20110035H     
2.0. Principal Investigator (PI):
   Nellis AFB PI:
Name
Paul Crawford, MD
Rank/Corps or Civilian Rating
Col
Date of IRB Approved CITI Training 
12/28/17
Branch of Service
USAF
AD Mil/DoD Civilian/Ctr/Non-DoD Civ
AD Mil
Department  & Base
Graduate Medical Education, Nellis AFB
Phone & Pager #
(702) 653-3298
E-Mail Address &
 AKO/DKO E-Mail 
Address
paul.f.crawford.mil@mail.mil
3.0. Research Plan:
3.1. Purpose:  
The purpose of this study is to assess whether water-soluble cinnamon extract plus aggressive lifestyle intervention is 
effective in lowering blood glucose in pre-diabetic patients when compared to aggressive lifestyle therapy plus placebo.
3.2. Hypotheses, Research Questions or Objectives: 
Does water-soluble cinnamon extract have an effect on fasting glucose, hemoglobin A1c, lipid panel, and waist 
circumference in pre-diabetic patients who are already undergoing aggressive lifestyle therapy?
This study has the following goals:
1. Determine the length of time to diagnosis of diabetes using any of the ADA criteria.
2. Determine:
a)
Fasting glucose,
b)
Hemoglobin A1c,
c)
LDL, cholesterol, and
d)
Waist circumference (in inches).
4. Brief Summary of the study:
We are studying whether water-soluble cinnamon extract (Cinnulin PF) plus standard of care aggressive lifestyle therapy
is effective in lowering blood glucose when compared to placebo plus standard of care aggressive life style therapy.
Eligible subjects will be recruited from any form and any stage of “standard” lifestyle intervention for pre-diabetes at an
individual base. “Standard” lifestyle intervention for pre-diabetes could include Group Lifestyle Balance (GLB), nutrition
classes, Better Body/Better Life, or anything an investigator certifies as standard practice at that base. Subjects will take
either 1 gram (2-500 milligram (mg) capsules) of water-soluble cinnamon extract (Cinnulin PF) or 2 placebo pills (gelatin
capsule filled with wheat bran) once a day for 1 year plus 1 additional year of follow-up. This is a randomized, double-
blind, multicenter, placebo-controlled study which will enroll subjects at the Mike O’Callaghan Military Medical Center at
Nellis AFB (Nellis AFB).  All subjects will be Nellis AFB DoD beneficiaries.  Informed Consent and HIPAA Authorization
will be obtained.  After randomization, subjects will receive either 1 gram (2-500 mg capsules) of water-soluble cinnamon
extract or placebo from the pharmacy--thus investigators and subjects will be blinded as to if they are taking Cinnulin PF
or 2 placebo pills. Subjects will be permitted to have usual medical care for other co-morbid, preventive, and acute
conditions.  Analysis will be performed using intention-to-treat principles for missing data (the carry-forward method to
impute missing data will be used).  Subjects will bring in any remaining water-soluble cinnamon extract or placebo to
determine adherence rates to the study protocol.
5. Subjects:
Subjects will be recruited from any form and any stage of “standard” lifestyle intervention for pre-diabetes at an individual
base. “Standard” lifestyle intervention for pre-diabetes could include Group Lifestyle Balance (GLB), nutrition classes,
Better Body/Better Life, or anything an investigator certifies as standard practice at that base.  No special populations (i.e.
children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged
persons) will be eligible for this study.


Revised by PR 2019
2
6. Inclusion/exclusion criteria: 
Inclusion:
•
Patients will be Nellis AFBDoD beneficiaries, ages 18-65 years.
•
Diagnosis of pre-diabetes (defined as a fasting plasma glucose (FPG) 100-125mg/dl, Hemoglobin A1c 5.7-6.4%, 
or a 2-hour oral glucose tolerance test (OGTT) 140-199).
Exclusion: 
•
Patients who are less than 18 yrs of age or greater than 65 years of age.
•
Patients who are known to have or develop during the study any of the following upon review of their medical 
record:
o
Diabetes Mellitus (defined as fasting plasma glucose (FPG) ≥126mg/dl, hemoglobin A1C ≥6.5%, or a 2-
hour oral glucose tolerance test (OGTT) ≥200mg/dl)
o
Stage 3 kidney disease or worse
o
Renal insufficiency defined as a glomerular filtration rate (gfr) of less than 60ml
o
Celiac disease
o
Insulinoma
o
Cushing’s disease
o
Hyperthyroidism
o
Acromegaly
o
Pheochromocytoma
o
Addison’s disease
o
Galactosemia
o
Glycogen storage disease
o
Hereditary fructose intolerance
•
Patients taking any of the following:
o
Cinnamon as a dietary supplement
o
Daily oral steroids
o
Warfarin
o
Hypoglycemic medication
o
Weight loss medication
o
Digoxin, lithium, phenytoin,  & theophylline (due to their narrow therapeutic indices)
•
Patients who are pregnant or breast feeding
•
Patients with a known allergy to cinnamon
•
Patients with a known allergy to wheat
7.  Number of Subjects:  TOTAL NUMBER OF SUBJECTS (nation-wide/study-wide):   557
8.  Use of an Investigational New Drug: 
a.
Generic Name and IND Number:  Cinnulin PF (cinnamomum burmanii),  IND# 114078
b.
Sponsor holder of the IND Number:  Paul Crawford, MD, LtCol, USAF, MC
c.
Justification for use:  N/A
9.  Use of an Investigational Device: N/A
10. Use of a Placebo: 2 placebo pills (gelatin capsule filled with wheat bran)


Revised by PR 2019
3
PROTOCOL FOR CLINICAL INVESTIGATION – NON-EXEMPT HUMAN
(Wilford Hall Ambulatory Surgical Center – WHASC)
1.  Title:
Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg 
blood glucose in pre-diabetics: A randomized, double-blind, multicenter, placebo-controlled TRIAL.
FWH20110035H                                                         
2.0. Principal Investigator (PI):
                           
Nellis AFB PI:
Name
Paul Crawford, MD
Rank/Corps or Civilian Rating
Col
Date of IRB Approved CITI Training & Date of AKO/DKO IRBNet 
Training 
12/28/2017
Branch of Service
USAF
AD Mil/DoD Civilian/Ctr/Non-DoD Civ
AD Mil
Department  & Base
Graduate Medical Education/Nellis AFB
Phone & Pager #
(702) 653-3298
E-Mail Address &
 AKO/DKO E-Mail Address
paul.f.crawford.mil@mail.mil
2.1. Associate Investigators (AI):  See attached A2 Study Personnel Form
2.2. Research Assistants (RA) & Coordinators (RC):  See attached A2 Study Personnel Form
2.3. The research relevance of this protocol focuses on: 
[] Diagnosis    [] Treatment    [] Medical Utilization/Managed Care    [x] Prevention    [] Medical Readiness    [] Other
2.4. Location(s):  
a. Collaborating Facilities:  None.
b. Air Force Sites seeking Regional IRB:
Air Force Sites
Name
Email
Phone
Nellis Air Force Base
Jill Clark, MBA/HCM, CCRP, 
CCRC
jill.m.clark15.ctr@mail.mil
(702) 653-
3298
c. List study sponsors: Integrity Nutraceuticals, Inc. and AFMSA/SG9S
3.  Research Plan: 
3.1. Purpose: 
The purpose of this study is to assess whether water-soluble cinnamon extract plus aggressive lifestyle intervention is 
effective in lowering blood glucose in pre-diabetic patients when compared to aggressive lifestyle therapy plus placebo.
3.2. Hypotheses, Research Questions or Objectives: 
Does water-soluble cinnamon extract have an effect on fasting glucose, Hemoglobin A1c, lipid panel, and waist 
circumference in pre-diabetic patients who are already undergoing aggressive lifestyle therapy?
This study has the following goals:
1. Determine the length of time to diagnosis of diabetes using any of the ADA criteria.
2. Determine: 
a)
Fasting glucose
b)
Hemoglobin A1C
c)
LDL cholesterol, and
d)
Waist circumference (in inches)
3.3. Significance:  
Lowering hemoglobin A1c is correlated with reduced complications in Type 2 diabetes (e.g., retinopathy, nephropathy, 
neuropathy, vascular disease, and death).  Water-soluble cinnamon extract is inexpensive, readily available, generally 
recognized as safe, and a non-pharmacological approach to management.  According to the 2010 American Diabetes 
Association Guidelines, lifestyle intervention is the most effective way for diabetes.  Historically, it has been difficult for 
subjects to adhere to lifestyle education programs and sustain meaningful weight loss without using significant resources, 
as in the Diabetes Prevention Study (NEJM, 2002).
3.4. Military Relevance: 
Diabetes not only has a high morbidity and mortality amongst military beneficiaries but also is a drain on the military’s 
medical budget.  If cinnamon is found effective, it may result in long-term health care cost savings and better outcomes for 
our patient population.  Diabetes research in the Air Force is needed to not only support its peacetime healthcare mission, 
but reduce Air Force health care costs, thereby freeing up funds to support other missions of the AFMS.


Revised by PR 2019
4
 
3.5. Background and Review of Literature: 
As the worldwide incidence and prevalence of diabetes increases, the search for dietary adjuncts to treat this life-altering 
disease becomes far ranging.  Cinnamon is purported to be a natural insulin sensitizer with adverse events of peri-oral 
dermatitis and stomatitis reported uncommonly with high intake.2  There is one report of a severe exacerbation of rosacea 
after initiation of cinnamon for treatment of diabetes.3 It is designated by the U.S. Food and Drug Administration as 
“Generally Recognized as Safe”.  This product was submitted to the FDA as an Investigational New Drug. 
Both in vitro and in vivo animal studies have shown that cinnamon is an insulin sensitizer.4,5 Kim et al. showed that 
intestinal glucosidase activity in rats was increased by cinnamon.5 Polyphenols within cinnamon have been identified as 
upregulators of mouse adipocyte insulin receptors.6 Peng and colleagues found that polyphenols from cinnamon inhibit 
the formation of advanced glycation end-products in bovine serum albumin.7 Cinnamon extract (CE), high in type A 
polyphenols, prevents fructose feeding-induced decreases in insulin sensitivity. CE improves the postprandial 
overproduction of intestinal apoB48-containing lipoproteins by ameliorating intestinal insulin resistance and may be 
beneficial in the control of lipid metabolism.8
Cinnamon may improve glycemic control and insulin sensitivity.9 To date, seven randomized trials studying cinnamon in 
humans with Type 2 diabetes have been published with conflicting results.10-15  The results of these studies are mixed.  
Two of these studies showed a possible effect of cinnamon on fasting serum glucose, but they did not examine 
hemoglobin A1c levels.10,11 One study showed no effect on plasma glucose.12 Two studies--one each in patients with Type 
1 and Type 2 diabetes--showed no effect of cinnamon on Hemoglobin A1c.13,14 Cinnulin PF® supplementation reduced 
fasting blood glucose and systolic blood pressure, and increased lean body mass in a randomized trial in men and women 
with the metabolic syndrome.16 A meta-analysis of these studies in divergent populations measuring different parameters 
showed no effect of cinnamon on hemoglobin A1c, glucose or lipids.17 Subsequently, a RCT of 109 patients compared 
add-on treatment with 1 gram daily of cinnamon over a 3 month period to usual care in a population of poorly controlled 
Type 2 diabetics, it found that cinnamon lowered hemoglobin A1c 0.83%--similar to some prescription drugs.15 This led to 
a call for more comparative effectiveness research of cinnamon versus prescription medications.18
There have been no trials assessing if water-soluble cinnamon extract is effective at lowering blood glucose.  Guidelines 
recommend that new diabetics receive treatment with Metformin to help with insulin sensitization, lower blood glucose, 
and assist with weight loss.  Water-soluble cinnamon extract appears to have many of the same mechanisms of 
Metformin. 
Research has shown that pre-diabetics convert to diabetes at an average of 7% a year and other research performed on 
prevention have been multi-year trials.  In order to obtain adequate power for this study, subjects will take water-soluble 
cinnamon extract or placebo for 1 year.
 
3.5.1. Bibliography:
1.
Nahas R, Moher M.  Complementary and alternative medicine for the treatment of type 2 diabetes.  Can Fam 
Physician. 2009 Jun; 55(6):591-6.
2.
Dugoua J, Seely D, Perri D, et al.  From type 2 diabetes to antioxidant activity: A systematic review of the safety 
and efficacy of common and cassia cinnamon bark.  Can J Physiol Pharmacol 2007;85:837-847
3.
Campbell TM, Neems R, Moore J.  Severe exacerbation of rosacea induced by cinnamon supplements.  J Drugs 
Dermatol. 2008 Jun; 7(6):586-7.
4.
Talpur N. Echard B. Ingram C. et al. Effects of a novel formulation of essential oils on glucose–insulin metabolism 
in diabetic and hypertensive rats: a pilot study.  Diab Obes Metab, 2005.  7:193–199.
5.
Kim SH, Hyun SH, Choung SY.  Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice.  J 
Ethnopharmacol 2006; 104:119–123.
6.
Cao H, Polansky MM, Anderson RA.  Cinnamon extract and polyphenols affect the expression of tristetraprolin, 
insulin receptor, and glucose transporter 4 in mouse 3T3-L1 adipocytes.  Arch Biochem Biophys 2007; 459:214–
222.
7.
Peng X, Cheng K, Ma J, et al. Cinnamon bark proanthocyadins as reactive carbonyl scavengers to prevent the 
formation of advanced glycation products.  J Agric Food Chem 2008; 56:1907–1911.
8.
Qin B, Polansky MM, Sato Y, Adeli K, Anderson RA.  Cinnamon extract inhibits the postprandial overproduction of 
apolipoprotein B48-containing lipoproteins in fructose-fed animals.  J Nutr Biochem. 2009 Nov; 20(11):901-8.  
Epub 2008 Nov 6.
9.
Solomon TP, Blannin AK.  Changes in glucose tolerance and insulin sensitivity following 2 weeks of daily 
cinnamon ingestion in healthy humans.  Eur J Appl Physiol. 2009 Apr; 105(6):969-76.  Epub 2009 Jan 22.
10. Khan A. Khattak KN. Safdar M. Anderson RA.  Ali Khan MM. Cinnamon Improves Glucose and Lipids of People 
With Type 2 Diabetes.  Diabetes Care.  2003. 26:3215-3218.
11. Vanschoonbeek K. BJW Thomassen, JM Senden, WKWH Wodzig.  LJC.  van Loon.  Cinnamon Supplementation 
Does Not Improve Glycemic Control in Postmenopausal Type 2 Diabetes Patients.  J. Nutr.  2006. 136: 977–980.
12. Mang B. Wolters M. Schmitt B. Et al. Effects of a cinnamon extract on plasma glucose, HBA, and serum lipids in 
diabetes mellitus type 2.  Eur J Clin Invest.  2006. 36:340-344.


Revised by PR 2019
5
13. Altschuler JA, Casella SJ, MacKenzie TA, Curtis KM.  The effect of cinnamon on A1C among adolescents with 
type 1 diabetes.  Diabetes Care.  2007 Apr; 30(4):813-6.  
14. Blevins SM, Leyva MJ, Brown J, Wright J, Scofield RH, Aston CE.  Effect of cinnamon on glucose and lipid levels 
in non insulin-dependent type 2 diabetes.  Diabetes Care.  2007 Sep; 30(9):2236-7.  Epub 2007 Jun 11.
15. Ziegenfuss TN, Hofheins JE, Mendel RW, Landis J, Anderson RA.  Effects of a water-soluble cinnamon extract on 
body composition and features of the metabolic syndrome in pre-diabetic men and women.  J Int Soc Sports Nutr. 
2006 Dec 28; 3:45-53.
16. Baker WL, Gutierrez-Williams G, White CM, Kluger J, Coleman CI.  Effect of cinnamon on glucose control and 
lipid parameters.  Diabetes Care.  2008; 31(1):41-43.
17. Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: A 
randomized, controlled trial.  J Am Board Fam Med. 2009; 22(5):507-512.
18. Fairman KA, Curtiss FR.  Call for comparative effectiveness research: lowering A1C with sitagliptin, saxagliptin, or 
cinnamon.  J Manag Care Pharm. 2009 Oct; 15(8):696-700.
19. The DPP Research Group.  N Engl J Med. 2002; 346:393-403.
20. UPMC DPSC website https://diabetesprevention.upmc.com/diabetesPrevention_ProfessionalServices.htm 
accessed 19 April 2010.
  
3.6. Research Design and Methods: 
We will recruit male and female subjects between the ages of 18-65 years old with a diagnosis of pre-diabetes.  Eligible 
subjects will be recruited from any form and any stage of “standard” lifestyle intervention for pre-diabetes at an individual 
base. “Standard” lifestyle intervention for pre-diabetes could include Group Lifestyle Balance (GLB), nutrition classes, 
Better Body/Better Life, or anything an investigator certifies as standard practice at that base.
To capture potentially eligible subjects, we will use one or more of the following recruitment strategies. The instructors of 
these “standard” lifestyle interventions will:
1.
Utilize the Marquees on base. The marquee will state “Pre-Diabetic, Contact (insert contact) for Cinnamon Trial, 
(insert phone number)
2.
Mail a recruitment letter to all participants. 
3.
Announce at the beginning of class that we have a research study that they may potentially be interested in and 
ask permission to forward their contact information along to the research staff.
Screening Visit:
•
Obtain signed Informed Consent Document and HIPAA Authorization (research-driven).
•
Record: Date of birth, gender, race, ethnicity, name of lifestyle intervention for pre-diabetes, current email address 
height (in inches), weight (in pounds), waist circumference (in inches) measurement, blood pressure, and whether 
subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of drug, strength and 
dose.
•
Women of childbearing potential will have a serum pregnancy test (5-10 milliliters (mls), approximately 1-2 teaspoons 
of blood) (research-driven).
•
Subjects will have the following research-driven blood test drawn which include:
o
Fasting comprehensive metabolic panel (liver function, renal function, plasma glucose tests) via 1 
venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn)
*Subjects who have had a fasting comprehensive metabolic panel test within the two weeks prior to Visit 
1 will not need to have this test repeated.
o
Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn)
*Subjects who have had a Hemoglobin A1c test within the two weeks prior to Visit 1 will not need to have 
this test repeated.
o
Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn)
*Subjects who have had a lipid panel within the two weeks prior to Visit 1 will not need to have this test 
repeated.
Visit 1 (Day 1 within-30 days of Screening Visit*labs must be re-done if greater than 2 weeks from Screening 
Visit):
•
Record: whether subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of 
drug, strength and dose.
•
Subjects will complete the RAND 36 Item Health Survey.
•
Subjects will be randomized by a non-investigator at the pharmacy.  We will use a random-number generator and 
use blocking to ensure roughly equal sample sizes.  Both subjects and investigators will be blinded to the study 
group assignments.  Subjects will be randomized by the pharmacy into one of two groups (research-driven):
o
Group 1: Will take (by mouth) 2 gelatin capsules that contains 1 gram (2-500 mg capsules) water-soluble 
cinnamon extract (Cinnulin PF) once a day for 1 year plus 2 years of follow-up plus standard of care 
aggressive lifestyle therapy.
o
Group 2: Will take (by mouth) 2 placebo capsules (gelatin capsule filled with wheat bran) once a day for 1 
year plus 2 years of follow-up plus standard of care aggressive lifestyle therapy.


Revised by PR 2019
6
•
Subjects will be provided a pill container to assist with remembering to take their IP and a bathroom scale to 
weigh themselves with (if available).
•
Subjects will be given a Study Medication Diary and will be instructed to bring it with them to next study visit.
•
Subjects will be told to fast for at least 10 hours prior to Visit 2.
Visit 2-Month 3 (90 days after Visit 1):
•
Record: Weight (in pounds), waist circumference (in inches), blood pressure, verify current email address , and 
whether subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of drug, 
strength and dose.
•
Study staff will record whether subject had any side effects to report to include cardiovascular procedures and 
events and other morbidity data (research-driven).
•
Subjects will bring in any remaining medication to determine adherence rates to the study protocol.
•
Research staff will collect the subject’s Study Medication Diary and issue them a new one.
•
Subjects will be told to fast for at least 10 hours prior to Visit 3.
•
Refill water-soluble cinnamon extract or placebo (research-driven).
•
Subjects will have standard of care blood test drawn to include:
o
Fasting comprehensive metabolic panel (liver function tests, renal function, and plasma glucose test) via 
1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a fasting comprehensive metabolic panel test within the two weeks prior to Visit 
2 will not need to have this test repeated.
o
Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn)
*Subjects who have had a Hemoglobin A1c test within the two weeks prior to Visit 2 will not need to have 
this test repeated.
o
Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn)
*Subjects who have had a lipid panel within the two weeks prior to Visit 2 will not need to have this test 
repeated.
Visit 3-Month 6 (90 days after Visit 2):
•
Record: Weight (in pounds), waist circumference (in inches), blood pressure, verify current email address , and 
whether subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of drug, 
strength and dose..
•
Study staff will record whether subjects had any side effects to report to include cardiovascular procedures and 
events and other morbidity data (research-driven).
•
Subjects will bring in any remaining medication to determine adherence rates to the study protocol.
•
Research staff will collect the subject’s Study Medication Diary and issue them a new one.
•
Subjects will be told to fast for at least 10 hours prior to Visit 4.
•
Refill water-soluble cinnamon extract or placebo (research-driven).
•
Subjects will have research-driven blood test drawn which include:
o
Fasting comprehensive metabolic panel (liver function tests, renal function, and plasma glucose test) via 
1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a fasting comprehensive metabolic panel test within the two weeks prior to Visit 
3 will not need to have this test repeated.
o
Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a Hemoglobin A1c test within the two weeks prior to Visit 3 will not need to have 
this test repeated.
o
Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a lipid panel within the two weeks prior to Visit 3 will not need to have this test 
repeated.
Visit 4-Month 9 (90 days after Visit 3):
•
Record weight (in pounds), waist circumference) (in inches), blood pressure, verify current email address , and 
whether subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of drug, 
strength and dose.
•
Study staff will also record whether subjects had any side effects to report to include cardiovascular procedures 
and events and other morbidity data (research-driven).
•
Subjects will bring in any remaining medication to determine adherence rates to the study protocol.
•
Research staff will collect the subject’s Study Medication Diary and issue them a new one.
•
Subjects will be told to fast for at least 10 hours prior to Visit 5.
•
Refill water-soluble cinnamon extract or placebo (research-driven).
•
Subjects will have standard of care blood test drawn to include:
o
Fasting comprehensive metabolic panel (liver function tests, renal function, and plasma glucose test) via 
1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a fasting comprehensive metabolic panel test within the two weeks prior to Visit 
4 will not need to have this test repeated.


Revised by PR 2019
7
o
Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn)
*Subjects who have had a Hemoglobin A1c test within the two weeks prior to Visit 4 will not need to have 
this test repeated.
o
Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn)
*Subjects who have had a lipid panel within the two weeks prior to Visit 4 will not need to have this test 
repeated.
Visit 5-Month 12 (90 days after Visit 4) *SUBJECTS STOP TAKING STUDY MEDICATIONS AT THIS VISIT:
•
Record weight (in pounds), waist circumference (in inches), blood pressure, verify current email address , and 
whether subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of drug, 
strength and dose.
•
Record whether subjects had any side effects to report to include cardiovascular procedures and events and 
other morbidity data (research-driven).
•
Subjects will complete the RAND 36 Item Health Survey.
•
Subjects will bring in any remaining medication to determine adherence rates to the study protocol.
•
Research staff will collect the subject’s Study Medication Diary.
•
Subjects will be told to fast for at least 10 hours prior to Visit 6.
•
Subjects will have research-driven labs drawn which include:
o
Fasting comprehensive metabolic panel (liver function, renal function, and plasma glucose) via 1 
venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a fasting comprehensive metabolic panel test within the two weeks prior to Visit 
5 will not need to have this test repeated.
o
Hemoglobin A1C via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a hemoglobin A1c test within the two weeks prior to Visit 5 will not need to have 
this test repeated.
o
Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a lipid panel within the two weeks prior to Visit 5 will not need to have this test 
repeated.
Visit 6-Month 15 (90 days after Visit 5):
•
Record weight (in pounds), waist circumference (in inches), blood pressure, verify current email address , and 
whether subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of drug, 
strength and dose.
•
Record whether subjects had any side effects to report to include cardiovascular procedures and events and 
other morbidity data (research-driven).
•
Subjects will be told to fast for at least 10 hours prior to Visit 7.
•
Subjects will have standard of care blood tests drawn including:
o
Fasting comprehensive metabolic panel (liver function tests, renal function, and plasma glucose) via 1 
venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a fasting comprehensive metabolic panel test within the two weeks prior to Visit 
6 will not need to have this test repeated.
o
Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a hemoglobin A1c test within the two weeks prior to Visit 6 will not need to have 
this test repeated.
o
Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a lipid panel within the two weeks prior to Visit 6 will not need to have this test 
repeated.
Visit 7-Month 18- (90 days after Visit 6):
•
Record weight (in pounds), waist circumference (in inches), blood pressure, verify current email address , and 
whether subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of drug, 
strength and dose.
•
Record whether subjects had any side effects to report to include cardiovascular procedures and events and 
other morbidity data (research-driven).
•
Subjects will be told to fast for at least 10 hours prior to Visit 8.
•
Subjects will have a research-driven blood tests draw which includes:
o
Fasting plasma glucose via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood).
*Subjects who have had a fasting glucose test within the two weeks prior to Visit 7 will not need to have 
this test repeated.
o
Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a hemoglobin A1c test within the two weeks prior to Visit 7 will not need to have 
this test repeated.
o
Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).


Revised by PR 2019
8
*Subjects who have had a lipid panel within the two weeks prior to Visit 7 will not need to have this test 
repeated.
Visit 8-Month 21 (90 days after Visit 7):
•
Record: Weight (in pounds), waist circumference (in inches), blood pressure, verify current email address , and 
whether subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of drug, 
strength and dose.
•
Study staff will also record whether subjects had any side effects to report to include cardiovascular procedures 
and events and other morbidity data (research-driven).
•
Subjects will be told to fast for at least 10 hours prior to Visit 9.
•
Subjects will have standard of care blood test drawn which include:
o
Fasting plasma glucose via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be 
drawn).
*Subjects who have had a fasting glucose test within the two weeks prior to Visit 8 will not need to have 
this test repeated.
o
Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a hemoglobin A1c test within the two weeks prior to Visit 8 will not need to have 
this test repeated.
o
Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a lipid panel within the two weeks prior to Visit 8 will not need to have this test 
repeated.
Visit 9-Month 24 (90 days after Visit 8):
•
Record: Weight (in pounds), waist circumference (in inches), blood pressure, verify current email address , and 
whether subject is taking any statins, fibrate, niacin or bile acid binding agent and, if yes, the name of drug, 
strength and dose.
•
Subjects will complete the RAND 36 Item Health Survey.
•
Study staff will also record whether subjects had any side effects to report to include cardiovascular procedures 
and events and other morbidity data (research-driven).
•
Subjects will have research-driven blood tests drawn which include:
o
Fasting plasma glucose via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be 
drawn).
*Subjects who have had a fasting glucose test within the two weeks prior to Visit 9 will not need to have 
this test repeated.
o
Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a Hemoglobin A1c test within the two weeks prior to Visit 9 will not need to have 
this test repeated.
o
Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood will be drawn).
*Subjects who have had a lipid panel within the two weeks prior to Visit 9 will not need to have this test 
repeated.
VISIT WINDOWS: Visits have a window of plus or minus 10 days. Subjects are encouraged to come in as close to the 90 day 
mark as possible since they are only given a 90 day supply of IP.  Postponement of any follow up visits (after subject 
stopped taking study medication) is authorized for up to 6 weeks in case of a temporary condition that would affect 
glucose tolerance (i.e. moderate to severe illness to be determined by study PI or Site AI).  A note to file documenting 
such shall be placed in the subject’s study folder and documented in the data collection form.
ADHERENCE TO STUDY ASSIGNMENTS: Adherence to study medication will be assessed via review of the “Study 
Medication Diary”. Compliance will be recorded both in paper format and in the electronic data collection tool. If a subject 
misplaces their Study Medication Diary, they will be asked to reproduce it from memory to the best of their ability. 
Subjects will be instructed to bring back all of the bottles regardless of whether there are empty or contain missed doses.
If at any time a subject stops taking their water-soluble cinnamon extract or placebo, they will remain in the study, will be 
instructed to return any pill bottles, and will continue follow-up in the study.  Regardless of the amount of missed doses, all 
subjects will remain in the study and continue with all the study related visits.  Research staff will document the missed 
doses and subjects will continue in the research study.  If the subject decides to re-start their water-soluble cinnamon 
extract or placebo, they will resume the study at their last documented visit (i.e. subject stops taking water-soluble 
cinnamon extract or placebo at Visit 4 and decides 1 year later that they wish to resume the study, their next visit would 
be Visit 5).
If a subject misplaces or loses their study medication, they will be instructed to return to the pharmacy and will be given a 
new bottle of their assigned study medication.  Since the pharmacy is not blinded, they will be able to give the medication 
that the subject was assigned.


Revised by PR 2019
9
If a subject forgets to bring their study medication in for their visit, they will be instructed to bring it in at their earliest 
convenience.
DIRECTIONS FOR TAKING MEASUREMENTS:  A measuring tape to measure subjects’ waist circumference will be 
provided to the study team.  A designated study staff member will obtain the waist circumference measurements to 
ensure consistent measurements throughout the study.
Directions for taking waist circumference measurement:  Have subject take a deep breath, blow out, and hold with 
abdominals tightened.  Tell subjects not to suck in their stomach.  Take the measurement around the largest part of their 
waist.  Waist circumference should be recorded to the nearest ½ inch (for example 40.5”).
Directions for weighing subjects:  Have subject remove his/her shoes and empty pockets of any items prior to stepping on 
the scale.  Weight should be recorded to the nearest ½ pound (for example 150.5#).
Directions for taking height:  Have subjects remove their shoes before taking their height.  Height should be recorded to 
the nearest 1/2 inch (for example 60.5”).
Directions for taking blood pressure: Have subjects sit for 5 minutes before taking blood pressure.
WITHDRAWAL PROCEDURES: If at any time during the study, the subject decides to withdraw consent they will be 
referred back to their Primary Care Manager (PCM).  If a subject is found to be diabetic during the course of the study, 
they will be withdrawn and referred to their PCM to initiate standard of care treatment. Standard of care typically follows 
the DoD Clinical Practice guidelines for self-monitoring of blood glucose. As part of this, the Air Force provides 
glucometers and supplies at no charge.
ADVERSE EVENTS (AEs) AND DEVIATIONS: The Associate Investigator (AI) at each site is responsible for reviewing, 
categorizing, and properly reporting to the main PI AEs that occur with their subjects. The “Algorithm for Determining 
Whether an Adverse Event is an Unanticipated Problem” is attached to assist in guiding the research staff on the 
categorizing of Adverse Events, Protocol Deviations, and Serious Adverse Events.
Serious Adverse Events (SAEs) and Serious Protocol Deviations  are defined as unexpected events that increase the 
risk to subjects and that were possibly, probably, or definitely related to the research.  These must be reported to the 
WHASC IRB within 5 days.  Each site is responsible for reporting these to Col Crawford, the local Site Principal 
Investigator, and Jill Clark immediately via the “Possible Internal (Local) Reportable Unanticipated Problem Involving Risk 
to Subjects or Others (UPIRSO)” form.
If a subject experiences an allergic reaction during the study, they will be instructed to stop taking the study medication 
and seek urgent medical treatment.
Adverse Events (AEs) and Protocol Deviations that do not increase the risks to subjects like those listed in the “risks” 
section of this protocol are to be reported to Col Crawford, the local Site Associate Investigator and Jill Clark as they occur 
or no later than the 1st workday of every month via the “WHASC Tracking Log for Adverse Events (AEs)/Protocol 
Deviations Not Requiring Immediate Reporting.  This is done to ensure ongoing monitoring and identification of trends that 
may arise.
Guidance for completing the SAE/AE forms:
•
When completing the forms, please ensure that you include as much information as possible, to include:
o
Date the patient reported the event
o
Date the event occurred or the date that you discovered the event happened/began
o
A detailed description of the event including any tests/procedures that were performed with dates
o
Any directions given to the patient including the date
o
Description of the resolution with the date
•
When answering the questions:
o
“Was the event unexpected?": Select YES only if the event was NOT already listed in the risks/benefits 
section of the Protocol or part of an existing disease process.
o
"Did the event cause increased risk to participants or others": Select YES only if the adverse event was 
serious, which includes events that are life threatening or results in: death, inpatient hospitalization, 
prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital 
anomaly/birth defect, or may jeopardize the subject's health and may require medical or surgical 
intervention to prevent one of the outcomes above. If the event is not serious but there is a trend that 
would warrant a change in the protocol/ICD (i.e. several patients experienced a rash), then you would 
also select YES.
o
"Was the event possibly, probably, or definitely related to the research procedures?": Select YES if it is 
due to the research itself not underlying disease or disorder. If there isn't adequate information available 
to assess this, the answer would be NO.


Revised by PR 2019
10
o
"Should the consent form/process be revised": Select YES only if it warrants a revision to the research 
process or risks/benefits (this should be discussed with Col Crawford if you are selecting YES).
o
"Summary of events in the opinion of the local investigator": please have your Local Site Associate 
Investigator comment such as "no increased risks to subjects participating in the study" (just an example). 
Then have your Site Associate Investigator sign, print their name, and date. Then return the scanned 
copy to Col Crawford and Jill Clark. They will then get the Research Monitor to complete Section 6, and 
return a copy to be filed in the subjects file.
PREGNANCY: Subjects must agree to take precautions to prevent pregnancy during the course of this study due to the 
possible effect water soluble cinnamon extract may cause an unborn child.  The only completely reliable methods of birth 
control are total abstinence or surgical removal of the uterus.  Other methods, such as the use of condoms, a diaphragm or 
cervical cap, birth control pills, IUD, or sperm killing products are not totally effective in preventing pregnancy.  In addition, 
women who are breastfeeding may not participate in this study.
If a subject unintentionally becomes pregnant, they will be instructed to cease water-soluble cinnamon extract or placebo, 
return any pill bottles and will continue follow-up in the study.  They will be encouraged to resume taking water-soluble 
cinnamon extract or placebo and blood work (if they choose) 6 months after delivery of their child.  If the subject decides to 
re-start their water-soluble cinnamon extract or placebo, they will resume the study at their last documented visit (i.e. 
subject stops taking water-soluble cinnamon extract or placebo at Visit 4 and decides 1 year later that they wish to 
resume the study, their next visit would be Visit 6).
SUBJECTS ENROLLED NO LONGER PRE-DM:  If a subject becomes no longer pre-diabetic while enrolled in the study, 
they will remain in the study.
SUBJECTS ENROLLED BECOME TYPE II DIABETIC:  If a subject becomes Type II diabetic while enrolled in the study, 
they will be removed from the study. 
SUBJECTS COMPLETING THE STUDY:  When subjects have completed the study, the Pharmacy will de-identify the 
information and send to the Investigator for analysis.  Each Associate Investigator will send the de-identified data to the 
Principal Investigator via an encrypted email for analysis.
HYPOGLYCEMIC EPISODES: If the subject experiences a hypoglycemic (low blood sugar) episode, e.g., for example 
heart palpitations (abnormal heart beats either fast or slow), tremors (involuntary muscle movement), hunger, sweating, they 
should be instructed to eat 15-20 grams of sugar (e.g., glucose (sugar) tablets, glass of juice or other snack containing sugar) 
then eat some carbohydrates (e.g., a small meal or cracker with peanut butter).
BLOOD TEST OUTSIDE OF NORMAL REFERENCE RANGE: Research Coordinators at each site will print the blood 
test results and place in the subject’s folder.  If any of these results are outside of the normal reference range noted by 
their lab, they will place a telephone consult for the subject’s Primary Care Manager (PCM).
DISPOSAL OF STUDY RELATED PILLS: Subjects will return any remaining study-related pills directly to the Research 
Coordinator or Principal Investigator. The Research Coordinator or Principal Investigator will be responsible for disposing 
of the study-related pills. The preferred method of disposal is to have the Pharmacy dispose of them. If the Pharmacy is 
unable to dispose of them, they will provide directions on safe disposal for the Research Coordinator or Principal 
Investigator to follow.
OTHER ITEMS: If at any time, a site needs more study medication, they should contact the main site at the Nellis AFB 
and request.  Integrity Nutraceuticals should not be contacted directly. Prior to ordering any standard of care labs, study 
staff will verify in AHLTA that the subject did not have that lab test within the previous timeframes documented in the study 
visits above.  In addition, CHCS has alerts built in that will alert the person entering the lab test that there is a pending 
order.
Subjects will take their water-soluble cinnamon extract or placebo daily and will be permitted to have the usual medical 
care for other co-morbid and acute conditions if applicable.  Analysis described above using intention-to-treat principles 
for any missing data will be used (we will use the carry-forward method to impute missing data).
The placebo will be a gelatin capsule filled with wheat bran, which does not increase the risks to subjects.
Each site’s Laboratory will be responsible for analyzing blood samples obtained at their site for this study.  Samples will 
be labeled as they would for standard laboratory draws.  All Laboratories follow Clinical Laboratory Improvement 
Amendments (CLIA) procedures when processing laboratory specimens mentioned in this research project.
This study involves the use of an investigational product (IP) called Cinnulin PF (water-soluble cinnamon extract).  This means 
that the product has not been approved by the Food & Drug Administration (FDA) for preventing or delaying the onset of 


Revised by PR 2019
11
diabetes.  However, the FDA has not objected to its use to study its effectiveness.  Water-soluble cinnamon extract (Cinnulin 
PF) is being used to assess its effects on insulin in pre-diabetic subjects.  It is being given in a dose that does not 
increase the risk to the research subjects.  There are no known risks associated with water-soluble cinnamon as it is a 
compound granted GRAS (Generally Recognized As Safe) status by the United States Food and Drug Administration 
(more information can be found at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=582.20).
3.6.1. Interventions, Observations, or Data Sought: 
We will assess effect of 1 gram (2-500 mg capsules) of water-soluble cinnamon extract taken once a day for 1 year plus 1 
year of follow-up and obtain fasting glucose, Hemoglobin A1c, lipid panel, height, weight, and waist circumference (in 
inches). Additionally, to assess safety of long term cinnamon use, electrocardiograms will be performed to evaluate for QT 
prolongation.
3.6.2. Data Collection and Processing: 
Subjects will be randomized by the pharmacy. Pharmacist acting as Associate Investigators will be unblinded to study 
medication assignments. At the conclusion of the study, Pharmacists will provide the blinded information to the Principal 
Investigator for analysis. Both subjects and Investigators will be blinded to the study assignments. Data will be collected 
and recorded in a spreadsheet. At the conclusion of the study, all personally identifying information will be removed prior 
to analysis based on AFI 33-332, “The Air Force Privacy and Civil Liberties Program” and the “National Institute of 
Standards and Technology Special Publication (NIST SP 800-88) for the approved methods to destroy PII”. Each subject 
will be asked to place their de-identified study-related data into the “Nellis Diabetes Research Data Repository 
(FWH20110136H)” for future research. If the subject does not give their authorization, then all de-identified study-related 
data will be destroyed no later than at the closure of the study.
3.6.3. Setting:  Mike O’Callaghan Military Medical Center at Nellis AFB.
3.6.4. Date(s): April 2012-April 2018
3.6.5. Source of Research Material: 
Source of Research Material per Participant (Procedures)
# Routine 
Care
# Research 
Driven
# Total 
Procedures
Group 1 Only: 1 gram (2-500 mg capsules) water-soluble 
cinnamon extract (Cinnulin PF) (once a day for 1 year)
0
1 year
1 year
Group 2 Only: 2 placebo pills (once a day for 1 year)
0
1 year
1 year
Fasting glucose
0
3
3
Fasting comprehensive metabolic panel
3
3
6
Hemoglobin A1C
4
5
9
ECG
0
2
2
Lipid panel
4
5
9
Study Medication Diary
0
4
4
RAND 36-Item Health Questionnaire
0
3
3
“All specimens collected at Nellis AFB will be kept at Nellis AFB and handled and disposed of in accordance with federal 
regulations.”  
3.6.6. Subjects: 
We will recruit male and female subjects Nellis AFB between the ages of 18-65 years with a diagnosis of pre-diabetes.  
Eligible subjects will be recruited from any form and any stage of “standard” lifestyle intervention for pre-diabetes at an 
individual base. “Standard” lifestyle intervention for pre-diabetes could include Group Lifestyle Balance (GLB), nutrition 
classes, Better Body/Better Life, or anything an investigator certifies as standard practice at that base.  No special 
populations (i.e. children, prisoners, pregnant women, mentally disabled persons, or economically or educationally 
disadvantaged persons) will be eligible for this study. There are currently 2,950 diabetic patients empaneled for care at 
Nellis AFB. Several thousand more are pre-diabetic--many of these will likely attain the diagnosis of diabetes within 36 
months. 
3.6.7. Inclusion/Exclusion Criteria: 
Inclusion:
•
Patients will be Nellis AFB DoD beneficiaries between the ages of 18-65 years.
•
Diagnosis of pre-diabetes (defined as a fasting plasma glucose (FPG) 100-125mg/dl or hemoglobin A1C 5.7-6.4% 
or a 2-hour oral glucose tolerance test (OGTT) 140-199).
Exclusion: 
•
Patients who are less than 18 yrs of age or greater than 65 years of age
•
Patients who are known to have or develop during the study any of the following upon review of their medical 
record:
o
Diabetes Mellitus (defined as fasting plasma glucose (FPG) ≥126mg/dl, hemoglobin A1C ≥6.5%, or a 2-
hour oral glucose tolerance test (OGTT) ≥200mg/dl)


Revised by PR 2019
12
o
Stage 3 kidney disease or worse
o
Renal insufficiency defined as a glomerular filtration rate (gfr) of less than 60ml
o
Celiac disease
o
Insulinoma
o
Cushing’s disease
o
Hyperthyroidism
o
Acromegaly
o
Pheochromocytoma
o
Addison’s disease
o
Galactosemia
o
Glycogen storage disease
o
Hereditary fructose intolerance
•
Patients taking any of the following:
o
Cinnamon as a dietary supplement
o
Daily oral steroids
o
Warfarin
o
Hypoglycemic medication
o
Weight loss medication
o
Digoxin, lithium, phenytoin, and theophylline (due to their narrow therapeutic index)
•
Patients who are pregnant or breast feeding
•
Patients with a known allergy to cinnamon
•
Patients with a known allergy to wheat
3.6.8. Instrumentation: N/A
4.0.  Human Subject Protection:
4.1. Recruitment: 
All potentially eligible patients will be offered an opportunity to participate. Primary Care Managers (PCMs) who are not 
part of the research team will be informed about the study and provided information on the inclusion/exclusion criteria. 
PCM referrals and posted advertisements will be utilized for recruiting subjects to the study. Some patients may be 
patients of the PI or AI, however, they will have the study staff recruit their patients to prevent any misconception of 
coercion or undue influence. If a potential subject is identified by the treating PCM and is interested in obtaining more 
information about the study, the patient will either be provided a contact number to the Research Staff, the Research Staff 
will be given the potential subject’s contact information by the PCM with the patient’s oral or written authorization, or the 
PCM will come and get the Research Staff to speak with the patient directly. Lifestyle Intervention instructors will also 
provide referrals with the patient’s oral or written authorization. We will also utilize the Marquees on base (the marquee 
will state: Pre-Diabetic, Contact (insert contact) for Cinnamon Trial, (insert phone number) for recruitment. 
We are requesting a HIPAA Waiver so we are able to review the AHLTA schedule for potential participants. The data 
collected will only be used for recruiting and will be destroyed after contact with individual patients has been made.  The 
clinical research coordinator will review the schedules of clinicians to find eligible patients within their schedule. The 
coordinator will proceed to inform the clinician of any possibly eligible subjects for the study.  Each participating clinic will 
mail their pre-diabetic patients a letter informing them of the Cinnamon trial, and giving them the opportunity to participate 
or opt out. The mailing of these letters will be tasked to a study team member at the study site. We are also requesting to 
obtain a list from the Disease Management nurse on behalf of Family Medicine and Family Health Clinics. This list will be 
used to mail out letters to potential participants to increase recruitment
4.2. Consent Processes: 
Informed consent and HIPAA authorization will be sought in advance from each prospective subject.  Informed consent 
will be appropriately documented.  [32 CFR 219.117] After discussion with the Investigator, the subject will be given the 
opportunity to consent.  The Investigator will provide a written copy of the consent form and allow the subject to read it, 
review it with the subjects, and answer questions.  The subject may decline to consent, and no pressure will be applied.  If 
the subject consents, the proper signatures will be obtained, and a copy will be given to the subject.
4.3 Participation Compensation: Subjects will not be paid for participation in this study.
4.4. Assent Process: N/A
4.5. Benefits: 
The benefits to the subjects may include lower hemoglobin A1c levels and improvement of long-term health by decreasing 
the risk of developing diabetes.
4.6. Risks: 


Re vise d b y P R 2 0 1 9
1 3
Ri s k s t o t h e s u bj e ct ar e mi ni m al a s t h e s u bj e ct s h a v e b e e n di a g n o s e d wit h pr e- di a b et e s a n d will h a v e t o b e tr e at e d 
r e g ar dl e s s if t h e y p arti ci p at e i n t hi s st u d y or n ot.  T h er e ar e n o k n o w n ri s k s a s s o ci at e d wit h w at er- s ol u bl e ci n n a m o n, a s it 
i s a c o m p o u n d gr a nt e d G R A S ( G e n er all y R e c o g ni z e d a s S af e) st at u s b y t h e U nit e d St at e s F o o d a n d Dr u g A d mi ni str ati o n. 
P ot e nti al ri s k s i n cl u d e t h e i n a d v ert e nt di s cl o s ur e of p er s o n al h e alt h i nf or m ati o n a n d a p ot e nti al f or a ci n n a m o n all er g y t h at 
i s n ot alr e a d y k n o w n b y t h e s u bj e ct.  T h e ri s k s a s s o ci at e d wit h t h e bl o o d dr a w i n cl u d e bl e e di n g, f e eli n g li g ht- h e a d e d, a n d 
br ui si n g at t h e bl o o d dr a w sit e a n d i nf e cti o n. Ri s k s a n d si d e eff e ct s r el at e d t o t h e w at er- s ol u bl e ci n n a m o n e xtr a ct i n cl u d e 
t h o s e, w hi c h ar e:
L e s s li k el y a n d n ot s eri o u s:
•
H y p o gl y c e mi a  (l o w bl o o d s u g ar):

H e art p al pit ati o n s ( a b n or m al h e art b e at s eit h er f a st or sl o w)

Tr e m or s (i n v ol u nt ar y m u s cl e m o v e m e nt)

H u n g er

S w e ati n g
*If a s u bj e ct e x p eri e n c e s a n y of t h e s e s y m pt o m s, t h e y ar e i n str u ct e d t o e at 1 5- 2 0 gr a m s of s u g ar [f or e x a m pl e 
gl u c o s e ( s u g ar) t a bl et s], a gl a s s of j ui c e or ot h er s n a c k c o nt ai ni n g s u g ar, a n d t h e n e at s o m e c ar b o h y dr at e s (f or 
e x a m pl e a s m all m e al or cr a c k er wit h p e a n ut b utt er).
L e s s Li k el y a n d s eri o u s
•
Ci n n a m o n a n d W h e at Br a n : T h er e m a y b e a ri s k t h at t h e s u bj e ct h a s a n all er g y t o ci n n a m o n a n d w h e at br a n 
t h at t h e y ar e n ot a w ar e of c urr e ntl y.  T h e si g n s a n d s y m pt o m s of a n all er gi c r e a cti o n i n cl u d e:
o
S h ort n e s s of br e at h
o
Hi v e s (it c h y r a s h)
o
R u n n y n o s e
o
W at er y e y e s
o
S or e e y e s
o
A st h m a
o
Li p s w elli n g
o
T o n g u e s w elli n g
o
N a u s e a
o
Br o c h o s p a s m ( a br o n c hi al s p a s m i s a s u d d e n c o n stri cti o n of t h e m u s cl e s i n t h e w all s of t h e br o n c hi ol e s)
o
A n a p h yl a xi s ( w h ol e- b o d y all er gi c r e a cti o n t h at h a s t h e f oll o wi n g si g n s a n d s y m pt o m s):

A b d o mi n al p ai n or cr a m pi n g

A b n or m al ( hi g h- pit c h e d) br e at hi n g s o u n d s

A n xi et y

C o nf u si o n

C o u g h

Di arr h e a

Diffi c ult y br e at hi n g

Diffi c ult y s w all o wi n g

F ai nti n g, li g ht- h e a d e d n e s s, di z zi n e s s

Hi v e s

It c hi n e s s

N a s al c o n g e sti o n

N a u s e a, v o miti n g

P al pit ati o n s

S ki n r e d n e s s

Sl urr e d s p e e c h

W h e e zi n g
*If t h e s u bj e ct e x p eri e n c e s a n y of t h e s e s y m pt o m s, t h e y ar e i n str u ct e d t o st o p t a ki n g t h e st u d y m e di c ati o n a n d 
s e e k ur g e nt m e di c al tr e at m e nt.
R ar e a n d s eri o u s
•
R A N D- 3 6 H e alt h Q u e sti o n n air e :  Ri s k s a n d si d e eff e ct s r el at e d t o t h e R A N D- 3 6 it e m H e alt h Q u e sti o n n air e i n cl u d e 
t h o s e w hi c h ar e:
o
T h er e i s a ri s k ( alt h o u g h r ar e) t h at t h e q u e sti o n n air e m a y i d e ntif y a s u bj e ct a s at ri s k f or a m e nt al h e alt h 
c o n diti o n a n d r e s ult i n a r ef err al t o m e nt al h e alt h.  O c c a si o n all y a p er s o n di a g n o s e d wit h a m e nt al h e alt h 
c o n diti o n m a y b e di s q u alifi e d fr o m a cti v e d ut y a n d a M e di c al E x a mi n ati o n B o ar d ( M E B) r ef err al.
4. 7. C o st s:  T h er e will b e n o a d diti o n al c o st s t o s u bj e ct s f or t h eir p arti ci p ati o n i n t hi s r e s e ar c h st u d y.
4. 8. S af e g u ar d s f or Pr ot e cti n g I nf or m ati o n:  
H o w will c o d e d or i d e ntifi a bl e d at a/ s p e ci m e n s b e 
st or e d ?


Revised by PR 2019
14
[X]
Paper data, including completed consent forms
The research consents and HIPAA Authorization 
Documents will be stored in a locked cabinet in a locked 
room with restricted access.
[X]
Electronic data
Medical records will be annotated to reflect the subject’s 
participation in a research study. All coded, de-identified 
research data will be electronically stored separately from 
the Master Key of identifiable patient demographics and 
PHI/PII.
[X]
Long-term storage (following completion of the 
study and inactivation of IRB approval)
The research data will be coded and any links to 
identifiable data will be destroyed (an approved shredding 
bin) as soon as possible or no later than at the closure of 
the study, with the exception of those study subjects that 
consent to place their de-identified research data into the 
“Nellis Diabetes Research Data Repository 
(FWH20110136H) for future research. The anonymized 
research data will not be utilized for further research 
activity beyond the protocol stipulations without additional 
IRB approval.  All de-identified research data will be 
maintained for 3 years following study closure.
4.9. Safeguards for Protecting Subjects: 
The Principal Investigator will be responsible for the protocol safety monitoring.  The PI will make study documents (e.g., 
consent forms, data pulls) and pertinent hospital or clinical records readily available for inspection by the local IRB and 
over sight staff for confirmation of the study data.  Integrity Nutraceuticals, Inc. will not have access to subjects’ medical 
records.
4.9.1. Minimizing Risks: 
Risks in this study are minimal and only relate to a blood draw and water-soluble cinnamon extract.  Subjects will have 
access to study personnel should they have any issues.  If there are any issues, they will be immediately reported to one 
of the Investigators and an applicable medical evaluation will be initiated.  There is also a risk of inadvertent breach of 
confidentiality.
  
4.9.2. Vulnerable Populations: No vulnerable populations will be recruited.
4.9.3. Clinical Care: 
If a subject experiences any injury, adverse event, or unexpected clinical finding, a PI, AI, or Primary Care Manager will 
be available to assess the subject and initiate proper clinical care.
4.9.4. Injury Compensation: Subjects will not be compensated for injuries.
4.9.5. Data Safety Monitoring: 
The trial will be conducted in compliance with this protocol, International Conference on Harmonization (ICH) Guidelines 
for Good Clinical Practice (GCP), and any applicable national and international regulatory requirements.  The Principal 
and Associate Investigators will be monitoring all aspects of the study in accordance with the appropriate regulations and 
will have regular meetings with periodic quality control of data documentation and collection.  The objectives of the 
monitoring meetings will be:
1) To verify the prompt reporting of all data points, including reporting SAE's and checking availability of signed informed 
consent,
2) To compare individual subject records, data pulls and/or the study source documents/case report forms (supporting 
data, laboratory specimen records and medical records to include physician progress notes, nurses’ notes, subjects’ 
hospital charts),
3) To ensure protection of study subjects, compliance with the protocol, and accuracy and completeness of records.
David Moss, DO, Capt (Primary) and Matthew Hawks, MD, Capt (alternate) will be the research monitors assigned to this 
study.
The PI will make study documents (e.g., consent forms, data pulls) and pertinent hospital or clinical records readily 
available for inspection by the local IRB and over sight staff for confirmation of the study data.
5.0. Alternatives: The alternative is not to participate in this study.
6.0. Data Analysis: 
6.1. Outcome Measures: 


Revised by PR 2019
15
We will be assessing the effect of 1 gram (2-500 mg capsules) of water-soluble cinnamon extract (Cinnulin PF) on pre-
diabetic subjects and obtaining hemoglobin A1c, lipid panel, height, weight, and waist circumference measurements (in 
inches).
6.2. Sample size estimation/power analysis: 
A priori power for H01 was assessed using G*Power Version 3.0.10 1. The results indicate 214 subjects per group with 8 
repeated measures for a total sample size of 3424 will achieve a power of approximately 0.99 to detect a small effect size 
of 0.10 at α = 0.0004.
A priori power for H02 was assessed using the method described by Glantz2 to calculate sample size for a two-sample 
log-rank test to detect differences in the time to event.  Based on this design, it will require a minimum of 214 subjects per 
group to detect a difference between a 17.5% conversion in the Placebo + lifestyle and an 11.5% conversion in the 
Cinnulin + lifestyle group at α = 0.05 (one-sided) and power of 0.80. 
We are enrolling 557 subjects total, for an expected 428 completing the study.  We estimate 129 subjects’ will either 
withdraw consent or drop out of the study.
6.3. Statistical Analysis: Statistical Analysis Plan
Protocol
Assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On 
loweriNg blood glucose in pre-diabetics: A randomized, double-blind, multicenter, placebo 
controlled TRIAL.
Principal 
Investigator(s)
Lt Col Paul Crawford, USAF, MC
99th MDG
Statistical Analysis 
Plan
Mr. Danny Sharon, Ctr
AFMSA/SG5M South
Statistical Analysis
Mr. Ken Williams, Ctr
 AFMSA/SG5M South
Technical Objective: The objective of this study is to compare Cinnulin PF, a cinnamon extract, in combination with a 
lifestyle management program, to a placebo and life style management program, and to evaluate the prevention or delay 
the development of Type 2 diabetes in persons with pre-diabetes.  
Sample: Subjects will be a random sample of males and females between the ages of 18-65 years with a diagnosis of 
pre-diabetes seen in certain Air Force medical treatment facilities.  The subjects are presumed to be randomly selected 
from the population of patients obtaining similar care at all Air Force medical treatment facilities. 
 Hypothesis:
H01 – No difference in means of continuous dependent variables between and among treatment groups
H02 – Cinnulin + Life Style and Placebo + Life Style groups have identical survival functions for the time to reach the Type 
2 diabetes conversion event.
Study Design: The experimental design of this study is a mixed effects, randomized complete block design with repeated 
measures.  Subject is a random effect as the subjects are a sample randomly selected and randomly assigned to a 
treatment group.  Fixed effects are treatment group and time of repeated measure as these effects cannot be generalized 
to other treatments and times.  Subjects will be randomly assigned to each treatment group.      
Factors:
1.
Subject
2.
Treatment: Cinnulin PF + Life Style Management versus Placebo + Lifestyle Management
3.
Repeated Measurements: Laboratory and physical measurements obtained from each subject at fixed intervals for the 
duration of the study (N=8).
1 Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and 
biomedical sciences. Behavior Research Methods. 2007; 39 (2): 175-191.
2 Glantz SA. Primer of Biostatistics. McGraw-Hill, 2002, 438-440.


Re vise d b y P R 2 0 1 9
1 6
O ut c o m e V ari a bl e s: 
1.
Di a b eti c i n di c at or s
a.
Gl u c o s e
b.
H e m o gl o bi n A 1 c
c. 
Li pi d p a n el ( c h ol e st er ol, tri gl y c eri d e s, H D L, L D L)
d.
W ai st cir c u mf er e n c e
2.
T y p e 2 di a b et e s c o n v er si o n:  Y e s/ N o
Ot h er V ari a bl e s of I nt er e st a m o n g S u bj e ct s
1.
S u bj e ct D e m o gr a p hi c s
a.
A g e ( y e ar s)
b.
M arit al St at u s ( si n gl e v er s u s m arri e d)
c.  
G e n d er
d.
R a c e/ Et h ni cit y ( Afri c a n A m eri c a n, E ur o p e a n A m eri c a n, or Hi s p a ni c, 2 p ar a m et er s)
e.
S p e ci alt y c o d e s ( c at e g ori z e d i nt o offi c e w or k, l o gi sti c s, or c o m b at s p e ci alti e s, 2 p ar a m et er s)
f.  
Milit ar y Gr a d e ( Offi c er gr a d e s c at e g ori z e d i nt o c o m p a n y, fi el d or hi g h er r a n k s; e nli st e d i nt o E 1 – E 6 or E 7 – 
E 9). 
S a m pl e Si z e E sti m ati o n a n d P o w er A n al y si s: A pri ori p o w er f or H 0 1 w a s a s s e s s e d u si n g G* P o w er V er si o n 3. 0. 1 0 3 .  
T h e r e s ult s s h o w n b el o w i n di c at e 2 1 4 s u bj e ct s p er gr o u p wit h 8 r e p e at e d m e a s ur e s f or a t ot al s a m pl e si z e of 3 4 2 4 will 
a c hi e v e a p o w er of a p pr o xi m at el y 0. 9 9 t o d et e ct a s m all eff e ct si z e of 0. 1 0 at α  = 0. 0 0 0 4.
I n p ut: 
Eff e ct si z e f
= 
0. 1
β/ α  r ati o
= 
4
T ot al s a m pl e si z e
= 
3 4 2 4
N u m b er of gr o u p s
= 
2
R e p etiti o n s
= 
8
C orr a m o n g r e p m e a s ur e s
= 
0. 8
O ut p ut:  
N o n c e ntr alit y p ar a m et er λ
= 
4 1. 5 0 3 0 3 0
Criti c al F
= 
1 2. 3 8 9 2 2 5
N u m er at or df
= 
1. 0 0 0 0 0 0
D e n o mi n at or df
= 
3 4 2 2
α  err pr o b
= 
0. 0 0 0 4 3 7 4 4 7
β  err pr o b
= 
0. 0 0 1 7 4 9 7 9
P o w er ( 1- β err pr o b)
= 
0. 9 9 8 2 5 0
0
0. 1
0. 2
0. 3
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
criti c al  F  =
1 2. 3 8 9 2
α
β
Fi g ur e 1.  r A N O V A P o w er, β  = 0. 0 0 2, α  = 0. 0 0 0 4, 2 1 4 s u bj e ct s p er gr o u p
P o st h o c a n al y s e s t o e v al u at e diff er e n c e s wit hi n cli ni c all y si g nifi c a nt ti m e i nt er v al s will b e t e st e d wit h o n e-t ail e d t-t e st s f or i n d e p e n d e nt s a m pl e s.  
T h e p o w er a n al y si s, u si n g G* P o w er V er si o n 3. 0. 1 0 4 , i s s h o w n b el o w a n d s h o w s 2 1 4 s u bj e ct s p er gr o u p will a c hi e v e a p o w er of a p pr o xi m at el y 
0. 8 5 t o d et e ct a s m all eff e ct si z e of 0. 2 0.  T o l e s s e n t h e pr o b a bilit y of a f al s e n e g ati v e, a β/ α  r ati o of 1 w a s e m pl o y e d.
t t e st s - M e a n s: Diff er e n c e b et w e e n t w o i n d e p e n d e nt m e a n s (t w o gr o u p s)
A n al y si s:  
C o m pr o mi s e: C o m p ut e i m pli e d α  & p o w er 
I n p ut: 
T ail( s)
=  
O n e
Eff e ct si z e d
= 
0. 2
β/ α  r ati o
= 
1
S a m pl e si z e gr o u p 1
= 
2 1 4
S a m pl e si z e gr o u p 2
= 
2 1 4
O ut p ut:  
N o n c e ntr alit y p ar a m et er δ
= 
2. 0 6 8 8 1 6
Criti c al t
= 
1. 0 3 5 0 1 5
Df
= 
4 2 6
α  err pr o b
= 
0. 1 5 0 6 2 4
β  err pr o b
= 
0. 1 5 0 6 2 4
P o w er ( 1- β err pr o b)
= 
0. 8 4 9 3 7 6
3  F a ul F, Er df el d er E, L a n g A- G, B u c h n er A. G* P o w er 3: A fl e xi bl e st ati sti c al p o w er a n al y si s pr o gr a m f or t h e s o ci al, b e h a vi or al, a n d 
bi o m e di c al s ci e n c e s. B e h a vi or R e s e ar c h M et h o d s . 2 0 0 7; 3 9 ( 2): 1 7 5- 1 9 1.
4 I bi d.


Re vise d b y P R 2 0 1 9
1 7
0
0. 1
0. 2
0. 3
- 3
- 2
- 1
0
1
2
3
4
5
criti c al  t =
1. 0 3 5 0 2
α
β
Fi g ur e 2.  t-t e st P o w er, β  = 0. 1 5, α  = 0. 1 5, 2 1 4 s u bj e ct s p er gr o u p
A pri ori p o w er f or H 0 2 w a s a s s e s s e d u si n g t h e m et h o d d e s cri b e d b y Gl a nt z 5  t o c al c ul at e s a m pl e si z e f or a t w o- s a m pl e 
l o g-r a n k t e st t o d et e ct diff er e n c e s i n t h e ti m e t o e v e nt.  B a s e d o n t hi s d e si g n, it will r e q uir e a mi ni m u m of 2 1 4 s u bj e ct s p er 
gr o u p t o d et e ct a diff er e n c e b et w e e n a 1 7. 5 % c o n v er si o n i n t h e pl a c e b o + lif e st yl e a n d a n 1 1. 5 % c o n v er si o n i n t h e 
ci n n uli n + lif e st yl e gr o u p at α  = 0. 0 5 ( o n e- si d e d) a n d p o w er of 0. 8 0. 
P o w er A n al y si s L o g- R a n k T e st f or T w o 
S a m pl e s
 
α  
0. 0 5 0
z . 0 5( 2) 
1. 6 4
1- β
0. 8 0
z . 8 0( u p p er)
- 0. 8 4 2
S 2 ( ∞)
0. 8 8 5
L n S 2( ∞)
- 0. 1 2 2 1 6 8
S 1 ( ∞)
0. 8 2 5
L n S 2( ∞)
- 0. 1 9 2 3 7 2
ψ
0. 6 3 5 0 5 9 7
d ( pri m ar y e n d p oi nt e v e nt s) =
1 2 4
n ( s a m pl e si z e t o a c hi e v e t hi s n u m b er of 
e v e nt s) =
4 2 8
Gr o u p s/ Tr e at m e nt s
2
S u bj e ct s r e q uir e d p er gr o u p/tr e at m e nt
2 1 4
St e p s of A n al y si s
D e s cri pti v e st ati sti c s: S a m pl e m e a n s a n d st a n d ar d err or s of m e a s ur e m e nt of i nt er v al v ari a bl e s will b e c al c ul at e d, a n d 
fr e q u e n c y di stri b uti o n s of n o mi n al v ari a bl e s will b e c al c ul at e d a n d gr a p h e d f or t h e t ot al s a m pl e a n d f or t h e 
Ci n n uli n/ Lif e st yl e M a n a g e m e nt gr o u p s.  H o m o g e n eit y of t h e gr o u p s will b e t e st e d wit h a t w o-t ail e d t-t e st a n d t w o-t ail e d 
Fi s h er’ s e x a ct t e st f or i nt er v al a n d n o mi n al v ari a bl e s r e s p e cti v el y. 
H y p ot h e si s T e sti n g
H 0 1 – T hi s h y p ot h e si s will b e t e st e d b y a mi x e d eff e ct s r e p e at e d m e a s ur e s a n al y si s of v ari a n c e (r A N O V A).
H 0 2 – T hi s h y p ot h e si s will b e t e st e d b y d e v el o pi n g K a pl a n- M ei er s ur vi v al c ur v e s a n d s ur vi v al f u n cti o n s c o m p ar e d wit h a 
l o g-r a n k t e st.
P o st H o c T e st s: I n t h e e v e nt H 0 1 i s r ej e ct e d, c o ntr a st s will b e u s e d t o i n v e sti g at e eff e ct s a n d diff er e n c e s wit hi n cli ni c all y 
si g nifi c a nt ti m e i nt er v al s. I n t h e e v e nt m ulti pl e u ni v ari at e t e st s ar e u s e d t o i n v e sti g at e eff e ct s, t h e B o nf err o ni 6  or H ol m’ s 
m et h o d
7  will b e u s e d t o c orr e ct t h e l e v el of si g nifi c a n c e f or m ulti pl e c o m p ari s o n s.
A n al y si s T o ol s:
S A S V er si o n 9. 2 f or Wi n d o w s ( S A S I n stit ut e, C ar y, N ort h C ar oli n a)
R V er si o n 2. 1 3. 1 ( R F o u n d ati o n f or St ati sti c al C o m p uti n g)
Mi cr o s oft E x c el ( Mi cr o s oft C or p or ati o n, S e attl e, W a s hi n gt o n)
6. 4 N u m b er of S u bj e ct s :  
N u m b er of s u bj e ct s r e cr uit e d at W H A S C
4 6
5 Gla ntz S A. Pri mer of Bi ost atistics . Mc Gra w- Hill, 2 0 0 2, 4 3 8- 4 4 0.
6 A b di H. B o nferr o ni a n d Ši dá k. C orrecti o ns f or m ulti ple c o m paris o ns. I n N.J. Sal ki n d (e d.). E ncycl o pe di a of Me as ure me nt a n d St atistics.  2 0 0 7; 
T h o usa n d Oa ks, C A: Sa ge.
7 H ol m, S. 1 9 7 9. A si m ple se q ue ntial rejecti ve m ulti ple test pr oce d ure. Sc a n d. J. St atistics , 6: 6 5- 7 0.


Revised by PR 2019
18
Number of subjects recruited at Nellis AFB
106
Number of subjects recruited at DGMC
76
Number of subjects recruited atEglin (actual)
53
Numerb of subject recruited at Offutt
2
TOTAL NUMBER OF SUBJECTS:  557 (nation-wide/study-wide):  428 (completing the study)
7. Duration of Study:  Approximate duration of the study:   6 years
8.  Intramural Funding/Local Support Services Required: 
We received a grant for Intramural funding from the AFMSA/SG9S in the amount of approximately $639,036.36.  We 
received a second grant from the 59MDW/ST for approximately $618,000 over 2 years. This is to support the salaries of 
four Medical Assistants, costs associated with Group Lifestyle Balance training, and site monitoring visits.
9.  Extramural Funding/External Support Services Required:  
Integrity Nutraceuticals, Inc. will provide Cinnulin PF and placebo to Geneva Research Foundation who will administer the 
grant.  Collaborating Institution Support: This study will be sponsored by Integrity Nutraceuticals, Inc.  The collaborative 
research will be executed in accordance with 15 USC 3710a through a Cooperative Research and Development 
Agreement, (pending approval) between the 99th MDG and Integrity Nutraceuticals, Inc.  Integrity Nutraceuticals, Inc. 
shall provide the Air Force activity: 1 gram (2-500 mg capsules) Cinnulin PF tablets for approximately 279 subjects taking 
once a day for 1 year ($280,370.00) and Placebo pills for approximately 279 subjects taking once a day for 1 year 
($1,870.00) to include shipping costs to the Air Force Activity.  The estimated fair market value of the support is 
$282,240.00.
10. Financial Conflict of Interest: No financial conflicts of interest exist.
11.  Use of an Investigational New Drug, use of a Drug for a non-FDA approved purpose, use of an investigative 
device or use of a placebo:  
This research uses an Investigational New Drug
[x] YES [] NO
This research uses a FDA approved drug for a non-FDA approved purpose                                                            [] YES
[x] NO
This research uses an Investigational Device     
[] YES [x] NO
This research uses a placebo.
                                                                                [x] YES
[] NO 
12.  Medical Research Area for the Study:  (Pick as many as appropriate)
[] Analytical Chemistry
[] Anatomy
[] Anesthesiology
[] Biochemistry
[] Cardiovascular Surgery
[] Cardiology
[] Cell Biology
[] Dentistry
[] Dermatology
[] Dietetics
[] Electrophysiology
[x] Endocrinology
[] Emergency medicine
[] Gastroenterology
[] General Surgery
[] Hematology
[] Histology
[] Immunology/Allergy
[] Infectious Disease
[] Microbiology
[] Molecular Biology
[] Neonatology
[] Neurology
[] Neurosurgery
[] Nursing
[] OB/GYN
[] Occupational Medicine
[] Occupational Therapy
[] Oncology
[] Ophthalmology
[] Oral/Maxillofacial Surgery
[] Orthopedics
[] Pathology
[] Pediatrics
[] Pharmacology
[] Physical Therapy
[] Mental Health
[] Radiology/Imaging
[] Urology
[] Wellness
[] Other (state): Family Medicine, Internal Medicine, Family Health Clinic
13. Attachments:
1.
Study Medication Diary
2.
Certificate of Compliance
3.
Informed Consent Document
4.
HIPAA Authorization Form
5.
Placebo justification
6.
Advertisement flyer
7.
Letter for Mailing
8.
Travis AFB Advertisement Flyer
9.
Investigational New Drug Worksheet
10. H33-Local and External Support Document
11. H32 Intramural and Extramural Funding Support Document
12. RAND 36-Item Health Questionnaire
13. Form A2-Study Personnel
14. Medication Disposal


Revised by PR 2019
19
15. Algorithm for Determining Whether an Adverse Event is an Unanticipated Problem
16. Form J HIPAA Waiver or Alteration

ICF_001.pdf: 
Cinnamon Trial-lIfestyle iNtervention Plus Water-soluble Cinnamon 
Extract On loweriNg Blood Glucose in Pre-diabetics
NCT01301521
January 24, 2018


Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in 
pre-diabetics: A randomized, double-blind, multicenter, placebo controlled TRIAL. 
For Protocol Office Use Only: 
FWH20110035H, ICD, Crawford, AMD 27 
Version: 1 Dec 12 
Page 1of 14 
Volunteer Name: __________________________________________________________  
WILFORD HALL AMBULATORY SURGICAL CENTER 
INFORMED CONSENT DOCUMENT 
Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On 
loweriNg blood glucose in pre-diabetics: A randomized, double-blind, multicenter, placebo controlled TRIAL. 
FWH20110035H 
INFORMATION ABOUT THIS CONSENT FORM:  
You may be eligible to take part in a research study. This form gives you important information about the study. You 
may be asked to sign in more than one place in this document. Please take time to review this information carefully. 
You should talk to the researchers about the study and ask them any questions you may have for them. You may also 
wish to talk to others (for example, your friends, family, or a doctor) about your participation in this study. If you 
decide to take part in the study, you will be asked to sign this form. Before you sign this form, be sure you understand 
the procedures of the study and what the study is about, including the risks and possible benefits to you.   
If you are taking part in another research study, please tell the researchers or study staff. 
VOLUNTARY PARTICIPATION:  
Taking part in this study is completely voluntary. You should not feel coerced or intimidated into participating in this 
project. You do not have to participate if you don't want to participate in the study. You do not have to participate in 
this study in order to get standard medical treatment. If significant new findings develop during the course of this 
study that may relate to your decision to continue to participate in the study, you will be informed. If you choose not 
to participate in this research study, your decision will not affect your eligibility for care or any other benefits to 
which you are entitled.   
PRINCIPAL INVESTIGATOR:  
The Principal Investigator (PI) is the researcher directing this study and is responsible for protecting your rights, safety, 
and welfare as a participant in the research. The PI for this study is: 
Principal Investigator: 
Mike O’Callaghan Military Medical Center, Nellis Air Force Base 
Col Paul Crawford, MD, USAF, MC 
Phone Number: (702) 653-3298  
Study Sponsor:  The Air Force Medical Support Agency (AFMSA), a federal agency, is providing funding for this 
study (the sponsor). The Principal Investigator designed the study and drafted the study plan. AFMSA is providing 
money to the 99 Medical Group so that the researchers can conduct the study. 


Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in 
pre-diabetics: A randomized, double-blind, multicenter, placebo controlled TRIAL. 
 
 
For Protocol Office Use Only: 
FWH20110035H, ICD, Crawford, AMD 27 
 
 
 
 
 
Version: 1 Dec 12 
 
Page 2of 14 
Integrity Nutraceuticals, a for-profit company, is funding this study (the sponsor). The Principal Investigator 
designed the study and drafted the study plan. Integrity Nutraceuticals provided the water-soluble cinnamon 
extract and placebo to the 99 Medical Group so that the researchers can conduct the study. 
 
Your participation in this study may provide financial benefit to the corporate sponsor. 
 
DESCRIPTION/PURPOSE OF RESEARCH (Why is this study being done?):  
You are being asked to consider participation in this research study. The purpose of this study is to see whether 
water-soluble cinnamon extract is effective in lowering blood glucose in patients undergoing aggressive lifestyle 
therapy. This study will have two groups of patients, Group 1 will take by mouth, 2 gelatin capsules that contains 1 
gram of water-soluble cinnamon extract (Cinnulin PF) once a day for 1 year and then be followed for an additional 1 
year plus standard of care aggressive lifestyle therapy. Group 2 will take by mouth, 2 placebo pills (gelatin capsule 
filled with wheat bran) once a day for 1 year, and then be followed for an additional 1 year plus standard of care 
aggressive lifestyle therapy. Investigators will then compare both groups to see if the use of the water-soluble 
cinnamon effect on fasting plasma (blood) glucose, hemoglobin A1c, lipid panel, and waist circumference. 
 
You are being asked to consider participation in this study because you have prediabetes. People with blood glucose 
(sugar) levels that are higher than normal but not yet in the diabetic range have "prediabetes”. People with 
prediabetes usually have no symptoms. You may have had prediabetes for several years without noticing 
anything. It is important to identify people with prediabetes because they have a higher risk of developing 
diabetes in the future. When you have high blood sugar over a long period of time your blood vessels in your 
heart, kidney, and eyes can get damaged. 
 
Aggressive lifestyle therapy is defined as participation in any standard lifestyle intervention that your doctor refers 
you to as part of your routine care.  
 
This study will enroll approximately 557 subjects at Nellis AFB. Your participation in this study will last approximately 
24 months. 
 
PHASE III STUDY:  
This study involves the use of an investigational product called Cinnulin PF (water-soluble cinnamon extract). This 
means that the product has not been approved by the Food & Drug Administration (FDA) for treating or preventing 
diabetes.  This study will help find out what effects, good and/or bad, of water-soluble cinnamon extract in lowering 
blood glucose. Cinnamon is supposed to be a natural insulin sensitizer, which means it helps the body return your 
blood sugar to normal. Insulin helps to control the amount of glucose (blood sugar) that is dissolved in the blood. 
Insulin prevents the blood sugar level from rising too high. The safety of this product in humans has been tested in 
prior research studies; however, some side effects may not yet be known.   
 
PROCEDURES:  
If you decide to take part in this research study, you will be asked to sign this consent form. During your participation 
in this study, you will be asked to make approximately 9 outpatient visits with the Principal Investigator (PI), an 


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Associate Investigator (AI), or study staff. It may be necessary for you to return to Nellis AFB for 24 months.  As a 
participant, you will undergo the following procedures:  
 
Screening Visit:  Exams, tests, and/or procedures may be done after you sign this consent to participate. This 
screening is done to find out if you can continue in the study (screening procedures). We may be able to use the 
results of exams, tests, and/or procedures you completed before enrolling in this study. You will be told which results 
we will obtain and which procedures will not have to be repeated. Any procedure described below as “standard care” 
would be done even if you do not take part in this research study. 
 
• 
Obtain signed Informed Consent document and HIPAA Authorization.  
• 
We will record your date of birth, gender, race, ethnicity, name of your lifestyle intervention for pre-diabetes, 
current email address, height (in inches), weight (in pounds), waist circumference measurement (in inches), blood 
pressure, and whether you are taking any statins, fibrate, niacin or bile acid binding agents. If yes, we need the 
name of drug, strength, and dose. 
• 
If you are capable of becoming pregnant, you will have a serum pregnancy test done (approximately 5-10 
milliliters (mls), 1-2 teaspoons of blood) (research-driven). 
• 
You will have the following blood tests: 
o Fasting comprehensive metabolic panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of 
blood). 
*If you’ve had a fasting comprehensive metabolic panel test within the 2 weeks before Visit 1, you will not 
have to have this test again. 
o Hemoglobin A1C via 1 venipuncture (5-10 milliliters (mls) approximately 1-2 teaspoons of blood) (research-
driven). 
*If you’ve had a Hemoglobin A1c test within the 2 weeks before Visit 1, you will not have to have this test 
again. 
o Lipid panel via 1 venipuncture (5-10 milliliters (mls) approximately 1-2 teaspoons of blood) (research-
driven). 
*If you’ve had a lipid panel test within the 2 weeks before Visit 1, you will not have to have this test again. 
This screening visit will take approximately 30 minutes. The results of the screening exams, tests, and/or procedures 
will be reviewed to determine whether you will be allowed to continue in the study. If you are not allowed to 
continue in the study, the researcher will discuss the reasons with you and will discuss other possible options. 
 
Visit 1 (Day 1-within 30 days of Screening Visit): 
• 
We will record whether you are taking any statins, fibrate, niacin, or bile acid binding agents. If yes, we need 
the name of drug, strength, and dose. 
• 
You will be asked to complete the Rand 36-Item Health Survey. 
• 
You will be randomly assigned (like flipping a coin) to 1 of 2 groups (research-driven): 
Group 1: Will take by mouth, 2 gelatin capsules that contain 1 gram water-soluble cinnamon extract (Cinnulin 
PF) once a day for 1 year, then be followed for 2 years plus standard of care aggressive lifestyle therapy). 
Group 2: Will take by mouth, 2 placebo pills (gelatin capsule filled with wheat bran) once a day for 1 year, 


Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in 
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then be followed for 2 years plus standard of care aggressive lifestyle therapy. 
• 
You will be provided a pill container to assist with remembering to take your study pills and a bathroom scale 
to weigh yourself. 
• 
You will be given a Study Diary that you will bring with you and give to the Research Staff at next study visit. 
• 
You will be told to fast (not eat or drink anything) for at least 10 hours prior to Visit 2. 
 
Visit 2-Month 3 (90 days after Visit 1): 
• 
We will record your weight (in pounds), waist circumference measurement (in inches), blood pressure, verify 
current email address, and whether you are taking any statins, fibrate, niacin, or bile acid binding agents. If 
yes, we need the name of drug, strength, and dose. 
• 
We will ask you if you have had any side effects to report including cardiovascular procedures and events and 
other morbidity data (research-driven). 
• 
You will bring in any remaining study pills and give to the research staff. 
• 
We will collect your Study Diary and issue you a new Study Diary. 
• 
You will be told to fast (not eat or drink anything, except water) for at least 10 hours prior to Visit 3. 
• 
We will refill your study pills at this visit (research-driven). 
• 
You will have the following standard of care blood tests: 
o Fasting comprehensive metabolic panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of 
blood). 
*If you’ve had a fasting comprehensive metabolic panel test within the 2 weeks before Visit 2, you will not 
have to have this test again. 
o Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a Hemoglobin A1c test within the 2 weeks before Visit 2, you will not have to have this test 
again. 
o Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a lipid panel test within the 2 weeks before Visit 2, you will not have to have this test again. 
 
Visit 3-Month 6 (90 days after Visit 2): 
• 
We will record your weight (in pounds), waist circumference measurement (in inches), blood pressure, verify 
current email address, and whether you are taking any statins, fibrate, niacin, or bile acid binding agents. If 
yes, we need the name of drug, strength, and dose. 
• 
We will ask you if you have had any side effects to report including cardiovascular procedures and events and 
other morbidity data (research-driven). 
• 
You will bring in any remaining study pills and give to the research staff. 
• 
We will collect your Study Diary and issue you a new Study Diary. 
• 
You will be told to fast (not eat or drink anything, except water) for at least 10 hours prior to Visit 4. 
• 
We will refill your study pills at this visit (research-driven). 
• 
You will have the following research-driven blood tests: 
o Fasting comprehensive metabolic panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons). 
*If you’ve had a fasting comprehensive metabolic panel test within the 2 weeks before Visit 3, you will not 


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have to have this test again. 
o Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons). 
*If you’ve had a Hemoglobin A1c test within the 2 weeks before Visit 3, you will not have to have this test 
again. 
o Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons). 
*If you’ve had a lipid panel test within the 2 weeks before Visit 3, you will not have to have this test again. 
 
Visit 4-Month 9 (90 days after Visit 3): 
• 
We will record your weight (in pounds), waist circumference measurement (in inches), blood pressure, verify 
current email address, and whether you are taking any statins, fibrate, niacin, or bile acid binding agents. If 
yes, we need the name of drug, strength, and dose. 
• 
We will ask you if you have had any side effects to report including cardiovascular procedures and events and 
other morbidity data (research-driven). 
• 
You will bring in any remaining study pills and give to the research staff. 
• 
We will collect your Study Diary and issue you a new Study Diary. 
• 
You will be told to fast (not eat or drink anything, except water) for at least 10 hours prior to Visit 5. 
• 
We will refill your study pills at this visit (research-driven). 
• 
You will have the following standard of care blood tests: 
o Fasting comprehensive metabolic panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of 
blood). 
*If you’ve had a Fasting comprehensive metabolic panel test within the 2 weeks before Visit 4, you will not 
have to have this test again. 
o Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you had a Hemoglobin A1c test within the 2 weeks before Visit 4, you will not have to have this test again. 
o Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a lipid panel test within the 2 weeks before Visit 4, you will not have to have this test again. 
 
Visit 5-Month 12 (90 days after Visit 4): 
• 
We will record your weight (in pounds), waist circumference measurement (in inches), blood pressure, verify 
current email address, and whether you are taking any statins, fibrate, niacin, or bile acid binding agents. If 
yes, we need the name of drug, strength, and dose. 
• 
We will ask you if you have had any side effects to report including cardiovascular procedures and events and 
other morbidity data. (research-driven) 
• 
You will be asked to complete the Rand 36-Item Health Survey. 
• 
You will bring in any remaining study pills and give to the research staff. 
• 
We will collect your Study Diary. 
• 
You will be told to fast (not eat or drink anything, except water) for at least 10 hours prior to Visit 6. 
• 
You will have the following research-driven blood tests: 
o Fasting comprehensive metabolic panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of 
blood). 


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*If you’ve had a Fasting comprehensive metabolic panel test within the 2 weeks before Visit 5, you will not 
have to have this test again. 
o Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a Hemoglobin A1c test within the 2 weeks before Visit 5, you will not have to have this test 
again. 
o Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a lipid panel test within the 2 weeks before Visit 5, you will not have to have this test again. 
 
Visit 6-Month 15 (90 days after Visit 5): 
• 
We will record your weight (in pounds), waist circumference measurement (in inches), blood pressure, verify 
current email address, and whether you are taking any statins, fibrate, niacin, or bile acid binding agents. If 
yes, we need the name of drug, strength, and dose. 
• 
We will ask you if you have had any side effects to report including cardiovascular procedures and events and 
other morbidity data (research-driven). 
• 
You will be told to fast (not eat or drink anything, except water) for at least 10 hours prior to Visit 7. 
• 
You will have the following standard of care blood tests: 
o Fasting comprehensive metabolic panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of 
blood). 
*If you’ve had a Fasting comprehensive metabolic panel test within the 2 weeks before Visit 6, you will not 
have to have this test again. 
o Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a Hemoglobin A1c test within the 2 weeks before Visit 6, you will not have to have this test 
again. 
o Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a lipid panel test within the 2 weeks before Visit 6, you will not have to have this test again. 
 
Visit 7-Month 18 (90 days after Visit 6): 
• 
We will record your weight (in pounds), waist circumference measurement (in inches), blood pressure, verify 
current email address, and whether you are taking any statins, fibrate, niacin, or bile acid binding agents. If 
yes, we need the name of drug, strength, and dose. 
• 
We will ask you if you have had any side effects to report including cardiovascular procedures and events and 
other morbidity data (research-driven). 
• 
You will be told to fast (not eat or drink anything, except water) for at least 10 hours prior to Visit 8. 
• 
You will have the following research-driven blood tests: 
o Fasting plasma glucose via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a fasting glucose test within the 2 weeks before Visit 7, you will not have to have this test 
again. 
o Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a Hemoglobin A1c test within the 2 weeks before Visit 7, you will not have to have this test 
again. 


Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in 
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o Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a lipid panel test within the 2 weeks before Visit 7, you will not have to have this test again. 
 
Visit 8-Month 21 (90 days after Visit 7): 
• 
We will record your weight (in pounds), waist circumference measurement (in inches), blood pressure, verify 
current email address, and whether you are taking any statins, fibrate, niacin, or bile acid binding agents. If 
yes, we need the name of drug, strength, and dose. 
• 
We will ask you if you have had any side effects to report including cardiovascular procedures and events and 
other morbidity data. (research-driven) 
• 
You will be told to fast (not eat or drink anything, except water) for at least 10 hours prior to Visit 9. 
• 
You will have the following standard of care blood tests: 
o Fasting plasma glucose via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons) 
*If you had a Fasting Glucose test within the 2 weeks before Visit 8, you will not have to have this test again. 
o Hemoglobin A1C via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons) 
*If you had a Hemoglobin A1C test within the 2 weeks before Visit 8, you will not have to have this test again. 
o Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons) 
*If you had a Lipid Panel test within the 2 weeks before Visit 8, you will not have to have this test again. 
 
Visit 9-Month 24 (90 days after Visit 8): 
• 
We will record your weight (in pounds), waist circumference measurement (in inches), blood pressure, verify 
current email address, and whether you are taking any statins, fibrate, niacin, or bile acid binding agents. If 
yes, we need the name of drug, strength, and dose. 
• 
You will be asked to complete the Rand 36-Item Health Survey. 
• 
We will ask you if you have had any side effects to report including cardiovascular procedures and events and 
other morbidity data (research-driven). 
• 
You will have the following research-driven blood tests: 
o Fasting plasma glucose via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a fasting glucose test within the 2 weeks before Visit 9, you will not have to have this test 
again. 
o Hemoglobin A1c via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a Hemoglobin A1c test within the 2 weeks before Visit 9, you will not have to have this test 
again. 
o Lipid panel via 1 venipuncture (5-10 mls, approximately 1-2 teaspoons of blood). 
*If you’ve had a lipid panel test within the 2 weeks before Visit 9, you will not have to have this test again. 
 
Your participation in this study is completed after Visit 9. Research has shown that cinnamon is effective in lowering 
hemoglobin A1c levels. Taking water soluble cinnamon extract does not increase the risks to most patients as 
cinnamon is a food additive and also a dietary supplement sold over the counter. 
 
Assignment to Study Groups: When it is determined that you are eligible for the study, you will be assigned by chance 


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(like flipping a coin) to 1 of 2 study groups. One group will have their standard of care diabetes treatment of 
aggressive lifestyle therapy plus placebo. The second group will have water-soluble cinnamon extract (Cinnulin PF) 
plus aggressive lifestyle therapy to see how it affects fasting glucose, hemoglobin A1c, lipid panel and waist 
circumference. You will have a one in 2 chance of being in the placebo group. A placebo is an inactive, harmless 
substance that looks like the water soluble cinnamon extract (Cinnulin PF). Neither you nor the researchers will know 
whether you are receiving standard treatment with placebo or water-soluble cinnamon extract. In the event of an 
emergency, there is a way for the researcher to find out which you are receiving. 
 
RISKS OR DISCOMFORTS: Risks from the specific research procedures (drug(s), interventions, or procedures) 
There are risks to taking part in this research study. One risk is that you may have side effects while on the study. Side 
effects can range from mild to serious. Serious side effects are those that may require hospitalization, are life 
threatening or fatal (could cause death).  The frequency that people experience a certain side effect can range from 
many (likely), few (less likely) or only one or two (rarely).  Side effects from this study will usually go away soon after 
you stop taking the water-soluble cinnamon extract (Cinnulin PF). The side effects related to the blood draw will 
usually go away soon after the blood draw has been completed. In some cases, side effects can be long lasting or may 
never go away. Everyone taking part in the study will be watched carefully for any side effects. However, the study 
doctors don’t know all the side effects that may happen. Be sure to tell your study doctor immediately, about any side 
effect that you have while taking part in the study. 
 
The following section will describe the risks related to each drug, intervention, or procedure that is part of this 
research study. You should talk to your study doctor about any side effects or other problems that you have while 
taking part in the study. Risks and side effects related to the water-soluble cinnamon extract (Cinnulin PF) include 
those which are: 
 
Less likely and not serious 
• Hypoglycemia (low blood sugar): 
o Heart palpitations (abnormal heart beats either fast or slow) 
o Tremors (involuntary muscle movement) 
o Hunger 
o Sweating 
*If you experience any of these symptoms, you should eat 15-20 grams of sugar (for example glucose (sugar) tablets, 
glass of juice or other snack containing sugar), then eat some carbohydrates (for example a small meal or cracker 
with peanut butter). 
 
Less Likely and serious 
• Cinnamon and Wheat Bran: There may be a risk that you have an allergy to cinnamon or wheat bran that you 
are not currently aware of. The signs and symptoms of an allergic reaction include: 
o Shortness of breath 
o Hives (itchy rash) 
o Runny nose 
o Watery eyes 


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o Sore eyes 
o Asthma 
o Lip swelling 
o Tongue swelling 
o Nausea 
o Brochospasm (a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles) 
o Anaphylaxis (whole-body allergic reaction that has the following signs and symptoms): 
 Abdominal pain or cramping 
 Abnormal (high-pitched) breathing sounds 
 Anxiety 
 Confusion 
 Cough 
 Diarrhea 
 Difficulty breathing 
 Difficulty swallowing 
 Fainting, light-headedness, dizziness 
 Hives 
 Itchiness 
 Nasal congestion 
 Nausea, vomiting 
 Palpitations 
 Skin redness 
 Slurred speech 
 Wheezing 
*If you experience any of these symptoms, stop taking the study medication and seek urgent medical treatment. 
 
Rare and Serious: 
• RAND-36 item Health Questionnaire: Risks and side effects related to the RAND-36 item Health Questionnaire 
include those which are: 
o There is a risk (although rare) that the questionnaire may identify you as at risk for a mental health condition and 
result in a referral to mental health. Occasionally a person diagnosed with a mental health condition may be 
disqualified from active duty and a Medical Evaluation Board (MEB) referral is made. 
 
There is also a risk of accidental release of confidential information. Cinnamon is a nutritional supplement and is 
generally regarded as safe for human consumption by the Food and Drug Administration (FDA). The water-soluble 
cinnamon extract under investigation in this study has not shown to cause birth defects.   For more information about 
risks and side effects, ask one of the researchers or study staff. 
 
As a FEMALE OF CHILDBEARING POTENTIAL wishing to volunteer for this project, you must not be pregnant and agree 
to take a pregnancy test before you participate in this study. You must also agree to take precautions to prevent 
pregnancy during the course of this study. The only completely reliable methods of birth control are total abstinence 


Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in 
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or surgical removal of the uterus. Other methods, such as the use of condoms, a diaphragm or cervical cap, birth 
control pills, IUD, or sperm killing products are not totally effective in preventing pregnancy. Also, you may not breast-
feed and participate in this study. If you become pregnant or feel you might be pregnant, contact your provider and 
the study investigator listed in the voluntary participation section. 
 
Are there risks if you also participate in other research studies?  Being in more than one research study at the 
same time, may increase the risk to you. It may also affect the results of the studies. You should not take part in 
more than one study without approval from the researchers. There may also be unforeseen risks associated with 
this or any research study. We will tell you about any significant new findings which develop during the course of 
this research which may relate to your willingness to continue taking part. 
 
WITHDRAWAL FROM THE STUDY:  
If you first agree to participate and then you change your mind, you are free to withdraw your consent and 
discontinue your participation at any time. Your decision will not affect your ability to receive medical care and 
you will not be penalized or lose any benefits to which you would otherwise be entitled. 
 
ARE THERE RISKS RELATED TO WITHDRAWING FROM THE STUDY? 
If you decide to withdraw from this study early, please discuss your decision with the Principal Investigator.  The 
researcher may ask you to complete study withdrawal procedures at a final study visit. There is no risk to you if you do 
not complete the final withdrawal procedures and you can choose not to participate in them.  
 
ADDITIONAL CIRCUMSTANCES OF WITHDRAWAL: The researcher may withdraw you from the study prior to the 
study’s end and the study medication may be stopped without your consent for one or more of the following 
reasons: 
• 
Failure to follow the instructions of the researchers and study staff. 
• 
The researcher decides that continuing your participation is not in your best interests. 
• 
You become ineligible to participate. 
• 
You need treatment not allowed in the study. 
• 
The study is cancelled. 
• 
Other administrative reasons. 
• 
Unanticipated circumstances. 
• 
If you experience an allergic reaction to the study medication. 
 
Should you be withdrawn from the study by the Investigator or study sponsor, the Investigator will refer you to 
your primary care provider. If you lose your status as a military health care beneficiary, you can no longer be 
included in the study. Please let the Principal Investigator and study staff know as soon as you become aware of 
your situation. The sponsor of this study may terminate the study and/or your participation in this study for safety 
reasons or if the drug receives FDA approval. There is no guarantee that the drug you received during this study 
will continue to be available through the military system. 
 


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BENEFITS:  
The investigators have designed this study to learn if the water-soluble cinnamon extract is as good as or better than 
or worse in lowering blood glucose in patients undergoing aggressive diabetic lifestyle therapy. However, there is 
no guarantee or promise that you will receive any benefit from this study other than knowing that the information 
may help future patients. The possible benefits of your participation in this study are that your hemoglobin A1c 
blood levels and your long term health may improve by decreasing your risk of developing diabetes.  
 
COSTS:   Will taking part in this study cost anything?  
The investigators have designed this study so that there is no cost to you to participate in this study other that what it 
will cost you to travel to the research appointments. The extent of medical care provided on this research protocol is 
limited and will be within the scope authorized for Department of Defense (DoD) health care beneficiaries. Your 
entitlement to medical and dental care is governed by federal laws and regulations. 
 
PAYMENT (COMPENSATION):  
You will not receive any compensation (payment) for participating in this study. 
 
ALTERNATIVES TO PARTICIPATION:  
Choosing not to participate in this study is your alternative to volunteering for the study. 
 
CONFIDENTIALITY OF RECORDS OF STUDY PARTICIPATION: Records of your participation in this study may only be 
disclosed in accordance with federal law, including the Federal Privacy Act, 5 U.S.C. 552a, and its implementing 
regulations. DD Form 2005, Privacy Act Statement – Military Health Records, contains the Privacy Act Statement for 
the records.This is to inform you this study meets the definition of an applicable clinical trial under Section 801 of 
the Food and Drug Administration Amendments Act (FDAAA 801), which requires responsible parties to register 
and submit summary results of applicable clinical trials with ClinicalTrials.gov. The law applies to certain clinical 
trials of drugs (including biological products) and medical devices. As a condition for the publication of research 
results generated by the clinical trial, the International Committee of Medical Journal Editors (ICMJE) also requires 
trial registration through ClinicalTrials.gov. The NCT number, NCT01301521, also called the ClinicalTrials.gov 
Identifier, can be used to obtain additional information about the registration of the clinical trial. 
 
By signing this consent document, you give your permission for information gained from your participation in this 
study to be published in medical literature, discussed for educational purposes, and used generally to further medical 
science. You will not be personally identified; all information will be presented as anonymous data.Your records may 
be reviewed by the U.S. Food & Drug Administration (FDA), the Air Force, the DoD, other government agencies that 
oversee human research, or the WHASC Institutional Review Board. 
 
A copy of this consent will be placed in your medical and/or research record.  A copy of this consent will be stored 
by the investigator in a locked cabinet in a locked room, as part of your research record.  Information collected on 
this study about you that will affect your medical care will be placed in your medical record.  Your medical record 
will be annotated to reflect you are participating in a research study. All information about you collected on this 
study will be kept in an electronic database, which will be double password-protected, firewall-protected and 


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access-restricted to people involved in this study.  As soon as possible, any link between your identity and the 
research information will be destroyed.  The research information collected about you for this study will not be 
used for any additional research activity beyond what you have approved by signing this consent. The study staff 
advises that you protect your copy of the informed consent document. A breach of confidentiality could occur if 
you inadvertently lose this document or allow others to view the document. In the unlikely event that you 
experience a loss of confidentiality, the study staff will take appropriate action to assist you.  Complete 
confidentiality cannot be promised, particularly for military personnel, because information regarding potential UCMJ 
violations or concerns regarding fitness for duty may be reported to appropriate medical, law enforcement, or 
command authorities. 
 
ENTITLEMENT TO CARE:  
The researchers have taken steps to minimize the known or expected risks. However, you may still experience 
problems or side effects, even though the researchers are careful to avoid them. If you believe that you have been 
harmed, notify the researchers as soon as possible. You may also need to tell your regular doctors. In the event of 
injury resulting from this study, the extent of medical care provided is limited and will be within the scope authorized 
for Department of Defense (DoD) health care beneficiaries. Your entitlement to medical and dental care and/or 
compensation in the event of injury is governed by federal laws and regulations, and if you have questions about your 
rights as a research subject or if you believe you have received a research-related injury, you may contact the Wilford 
Hall Chief, Clinical Research, (210) 292-7069 or the WHASC Risk Manager, (210) 292-6004, or at the facility that 
enrolled you in this study: 
 
• 
Mike O’Callaghan Military Medical Center Human Subject Protection Contact, (702) 653-3298 
 
If you sign this form, you do not give up your right to seek additional compensation if you are harmed as a result of 
being in this study. 
 
BLOOD, TISSUE & BIOLOGICAL SAMPLES:  
All blood samples kept at Nellis AFB will be handled and disposed of in accordance with federal regulations. 
Laboratories outside of these medical sites will not have permission to use the samples for any additional research. 
 
PROTECTED HEALTH INFORMATION (PHI) AND PERSONAL IDENTIFYING INFORMATION (PII) DATA: 
All PHI and PII data that will be used in the database repository will be kept at the Mike O’Callaghan Military 
Medical Center (Nellis AFB), Department of Family Medicine Residency and will be handled and disposed of in 
accordance with federal regulations. No unauthorized individual or agency outside of Nellis AFB will have access 
to this database without permission of the Database Repository, Manager Col Paul Crawford, and the Wilford Hall 
Ambulatory Surgery Center (WHASC) Institutional Review Board (IRB). 
 
The Investigators are asking for your permission to store your PHI and PII in the database repository for future use 
in research studies. The specifics of these research studies are unknown at this time, but these studies will 
frequently be in the areas of diabetes and preventative care. Your stored PHI and PII will be information such as 
gender, birth date, age, height/weight, medical history, laboratory tests, blood pressure, waist circumference 


Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in 
pre-diabetics: A randomized, double-blind, multicenter, placebo controlled TRIAL. 
 
 
For Protocol Office Use Only: 
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measurements and surgical procedures and post-surgery outcomes. This data is considered both identifying and 
non-identifying information and may be traced back to you as a donor when added to a database. The Principle 
Investigator and Database Repository Manager will take every precaution possible to safeguard your information 
to eliminate the possibility of any breach of confidentiality. This is explained below in the section, 
“Confidentiality”. The Database Repository Manager, Col Paul Crawford, is responsible for all PHI and PII data 
stored in the repository. All recipient investigators requesting data from the repository must have approval from 
the Database Repository Manager and must have a research study approved through a DoD Institutional Review 
Board (IRB) and the WHASC IRB. Only de-identified data (no personal identifiers or information) will be released to 
recipient investigators, so specific information can’t be traced back to the donor of the data. Recipient 
investigators may only receive limited data sets of de-identified information necessary to conduct their research. 
Generally, you will not be provided with the results of these research studies using your de-identified data from 
the repository. Any results would be of unclear value and unknown clinical meaning, since your de-identified data 
will be combined with other de-identified data from numerous patients used for the study. 
 
You may request that your PHI and PII data be withdrawn from the database repository at any time, if you decide 
you no longer want to participate. This request may be accomplished by calling the Database Repository Manager 
at Col Paul Crawford or mailing your request to the following address: Col Paul Crawford, MD, c/o Department of 
Medical Education, 4700 Las Vegas Blvd North, Nellis AFB, NV 89191. 
 
_______NO: I do not authorize the storage of my PHI and PII data for future use in research studies. 
 
_______YES:  I authorize the storage of my PHI and PII data for future use in research studies. 
 
 
_____________________________________________________ 
Signature of Study Participant 
 
CONTACT INFORMATION:  
The Principal Investigator or a member of Nellis Family Medicine Residency staff will be available to answer any 
questions concerning procedures throughout this study. 
 
Principal Investigator: 
Mike O’Callaghan Military Medical Center, Nellis Air Force Base 
Col Paul Crawford, MD, USAF, MC 
Phone Number: (702) 653-3298  
 
Institutional Review Board (IRB): The WHASC Institutional Review Board (IRB), the hospital committee responsible for 
safeguarding your rights as a research subject, has assigned a member of the IRB, who is not part of the study team, 
to serve as an outside monitor for this study (this person is the Research Monitor). If you have any questions about 
your rights as a research subject, research-related injuries or any other concerns that cannot be addressed by the PI, 
you can contact the research monitors Maj David Moss (Primary) or Capt Matthew Hawks at (702) 653-3298. Or mail 


Cinnamon Trial—assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in 
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For Protocol Office Use Only: 
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to: Clinical Investigation Program, 4700 Las Vegas Blvd North, Nellis AFB, NV 89191.In addition, if you have any 
comments, questions, concerns or complaints, you may also contact the Chairperson of the WHASC IRB   at (210) 916-
8251. Or mail to: 59th Medical Wing/CMO, 1100 Wilford Hall Loop, Lackland Air Force Base, TX 78236. Your consent 
to participate in this study is given on a voluntary basis. All oral and written information and discussions about this 
study have been in English, a language in which you are fluent. If you agree to participate in this research study, 
please sign this section. You do not waive any of your legal rights by signing this form.   
 
SIGN THIS FORM ONLY IF THE STATEMENTS LISTED BELOW ARE TRUE: 
• 
You have read the above information. 
• 
Your questions have been answered to your satisfaction.   
 
A signed copy of this form has been given to you. 
 
 
 
_________________________________________ 
 
 
__________________  
VOLUNTEER'S SIGNATURE 
 
 
 
 
DATE 
 
 
_________________________________________                                      
VOLUNTEER'S PRINTED NAME                                               
 
 
 
 
_________________________________________           ______________     (____)_______-__________ 
ADVISING INVESTIGATOR'S SIGNATURE  
         DATE 
 
       PHONE# 
 
 
______________________________________________ 
 
 
 
 
PRINTED NAME OF ADVISING INVESTIGATOR 
 
 
_______________________________________________ 
    ________________________  
WITNESS' SIGNATURE  
 
 
 
    DATE 
(Must witness ALL signatures) 
 
 
________________________________________________ 
PRINTED NAME OF WITNESS