Impaired Glucose Tolerance, Obesity
Conditions
Keywords
obesity, double blind, placebo controlled, weight loss, appetite, energy expenditure
Brief summary
This study will look at the effect of exenatide, a drug which has been approved for the treatment of type 2 diabetes, on body weight, appetite and energy expenditure among moderately obese women without diabetes. The study is 35 weeks long and includes 19 outpatient visits. Participants will receive exenatide for 16 weeks and placebo for 16 weeks with a 3 week rest period in between. Neither participants nor investigators will know whether exenatide or placebo is being administered. Participants will be started randomly on either exenatide or placebo. Our hypothesis is that treatment with exenatide will curb appetite and lead to weight loss and may lead to changes in energy expenditure.
Detailed description
This study will examine the effect of exenatide on body weight, energy expenditure, satiety, sleep, and metabolic parameters in healthy, moderately obese women (BMI 28-35 kg/m2). We will look at 2 populations of women, one with normal glucose metabolism and one with impaired glucose homeostasis (IGH)--either impaired fasting glucose (IFG, fasting glucose 101-125 mg/dL) or impaired glucose tolerance (IGT, glucose 140-199 mg/dL 2h after a 75g oral glucose load). This is a randomized, double blind, crossover study with two 16-week treatment periods separated by a 3-week washout period. There are 19 study visits over 35 weeks. The goals of this study are 1) to examine the effect of exenatide on body weight and dysglycemia in populations in which this medication has not been studied, namely obese women with and without IGH and 2) to investigate possible mechanisms of weight loss through measurements of energy expenditure, hunger, satiety, nausea, and sleep. The primary outcome of this study is weight loss. We will calculate absolute and relative change in body weight from baseline to week 16 (the first treatment period) and from week 19 to week 35 (the second treatment period). Body weight will be measured at every study visit which will also allow us to assess the absolute and relative change from baseline throughout the entire study.
Interventions
DRUGexenatide
5 microgram twice a day for two week and then 10 mcg for remaining 15 weeks
DRUGPlacebo
Twice daily injection of placebo
Sponsors
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Females aged 25-60 2. BMI 28-35 kg/m2 3. No known diagnosis of diabetes 4. No known diagnosis of coronary heart disease 5. Self-described sedentary lifestyle with minimal regular cardiovascular exercise (no more than 1 hour per week) 6. Stable weight (variation \< 3 kg within 6 months of screening visit) 7. Ability to give informed consent 8. Ability to follow verbal and written instructions 9. Use of medically approved form of contraception (monophasic oral contraception, intra uterine device, surgical sterilization or 2 combined barrier methods) 10. Nonsmoker (tobacco, marijuana) 11. Outpatient visits every 2 weeks throughout the study period are required. While most of these visits are short (15 minutes)ability to commute to the performance site in Boston, on a regular basis, is necessary.
Exclusion criteria
1. Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes Association criteria 2. Coronary heart disease (history of myocardial infarction or unstable angina pectoris) 3. Uncontrolled hypertension hypertension (BP \> 150/90 mmHg on or off antihypertensive medication) 4. Uncontrolled dyslipidemia (LDL \> 200 or TG \> 400 on or off lipid lowering medication) 5. Tobacco, marijuana or intravenous drug use 6. Shift workers (night shift or alternating day/night shifts) 7. Recent weight loss (\> 3 kg within 4 months of the screening visit) 8. Gastroparesis 9. Inflammatory bowel disease 10. Malignancy treated with chemotherapy within the past 3 years 11. History of pancreatitis 12. Depression requiring hospitalization or diagnosis of psychosis 13. Renal insufficiency (creatinine clearance \< 50 ml/min) 14. Transaminases \> 2x above the normal range 15. Pregnancy within 6 months of the screening visit 16. Breastfeeding 17. Failure to use medically approved contraceptive methods 18. History of an eating disorder (anorexia, bulimia or laxative abuse) 19. History of surgery for the treatment of obesity (gastric banding, gastric bypass, gastric stapling) 20. New diagnosis of hypo or hyperthyroidism within 1 year of screening visit 21. Previous participation in a clinical study with exenatide 22. Presence or history of allergic reaction to multiple drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weight | 16 weeks after the beginning of each treatment | Change in weight at the end of each treatment period. |
| Change in Body Mass Index | 16 weeks from the start of each treatment period. | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Body Composition | 16 weeks after the beginning of each treatment | Per cent body body fat was assessed using bio-electrical impedance with a BIA; RJL System Quantum II Bioelectrical Body Composition Analyzer. The data is reported as per cent body fat. |
| Changes in Leptin | 16 weeks from the start of each treatment period. | — |
| Diastolic Blood Pressure | 16 weeks after the beginning of each treatment | — |
| Adiponectin | 16 weeks after the beginning of each treatment | — |
| Change in Waist Circumference | 16 weeks from the start of each treatment period. | — |
| Change in Fasting Glucose | 16 weeks from the start of each treatment period. | — |
| Change in Two Hour Glucose | 16 weeks from the start of each treatment period. | — |
| HOMA Score | 16 weeks from the start of each treatment period. | — |
| REE | 16 weeks from the start of each treatment period. | Resting Energy Expenditure |
| Change in Insulin | 16 weeks from the start of each treatment period. | — |
| Systolic Blood Pressure | 16 weeks after the beginning of each treatment | Blood pressure was measured using a Dynamap automated monitoring device. The change is reported as the blood pressure measured at the beginning of the treatment group and after 16 weeks. We are reporting the change in the systolic blood presssure recorded. |
Countries
United States
Participant flow
Recruitment details
Flyers, Craig's list, posters used for recruitment.Recruitment occurred between 2007 and 2010. After telephone screen subjects were evaluated at the BIDMC clinical research center.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants in the study. | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Adiponectin | 6 micrograms/ml STANDARD_DEVIATION 3 |
| Age, Continuous | 48 years STANDARD_DEVIATION 11 |
| BMI | 33 Kg/meter^2 STANDARD_DEVIATION 4 |
| Body Fat | 40 percent STANDARD_DEVIATION 5 |
| Diastolic BP | 75 mm of Mercury STANDARD_DEVIATION 8 |
| Fasting Glucose | 85 mg/dl STANDARD_DEVIATION 12 |
| Fasting Insulin | 8 mU per liter STANDARD_DEVIATION 6 |
| HDL | 62 mg/dl STANDARD_DEVIATION 19 |
| HOMA IR | 2 Ratio STANDARD_DEVIATION 1 |
| LDL | 114 mg/dl STANDARD_DEVIATION 28 |
| Leptin | 36 ng/ml STANDARD_DEVIATION 18 |
| Region of Enrollment United States | 41 participants |
| Resting Energy Expenditure | 1439 Kilocalories STANDARD_DEVIATION 196 |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 0 Participants |
| Systolic BP | 128 mm of mercury STANDARD_DEVIATION 14 |
| Total Cholesterol | 198 mg/dl STANDARD_DEVIATION 32 |
| Triglycerides | 111 mg/dl STANDARD_DEVIATION 64 |
| Two Hour Glucose | 110 mg/dl STANDARD_DEVIATION 32 |
| Waist | 105 centrimeters STANDARD_DEVIATION 12 |
| Weight | 89 Kilograms STANDARD_DEVIATION 14 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 41 |
| other Total, other adverse events | 31 / 41 |
| serious Total, serious adverse events | 0 / 41 |
Outcome results
Primary
Change in Body Mass Index
Time frame: 16 weeks from the start of each treatment period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Change in Body Mass Index | -0.93 Kg/m^2 |
| Placebo | Change in Body Mass Index | 0.18 Kg/m^2 |
Primary
Change in Weight
Change in weight at the end of each treatment period.
Time frame: 16 weeks after the beginning of each treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in Weight | -2.49 kilograms | Standard Error 0.66 |
| Placebo | Change in Weight | 0.43 kilograms | Standard Error 0.63 |
Secondary
Adiponectin
Time frame: 16 weeks after the beginning of each treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Adiponectin | 0.4 microgram per ml |
| Placebo | Adiponectin | 0.07 microgram per ml |
Secondary
Change in Fasting Glucose
Time frame: 16 weeks from the start of each treatment period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Change in Fasting Glucose | 0.5 mg/dl |
| Placebo | Change in Fasting Glucose | 3.1 mg/dl |
Secondary
Change in Insulin
Time frame: 16 weeks from the start of each treatment period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Change in Insulin | 1.1 microunits per liter |
| Placebo | Change in Insulin | 0.4 microunits per liter |
Secondary
Change in Two Hour Glucose
Time frame: 16 weeks from the start of each treatment period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Change in Two Hour Glucose | -10 mg/dl |
| Placebo | Change in Two Hour Glucose | -0.5 mg/dl |
Secondary
Change in Waist Circumference
Time frame: 16 weeks from the start of each treatment period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Change in Waist Circumference | -1.68 centimeters |
| Placebo | Change in Waist Circumference | 0.94 centimeters |
Secondary
Changes in Body Composition
Per cent body body fat was assessed using bio-electrical impedance with a BIA; RJL System Quantum II Bioelectrical Body Composition Analyzer. The data is reported as per cent body fat.
Time frame: 16 weeks after the beginning of each treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Changes in Body Composition | -0.4 per cent |
| Placebo | Changes in Body Composition | -0.7 per cent |
Secondary
Changes in Leptin
Time frame: 16 weeks from the start of each treatment period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Changes in Leptin | -3.7 ng/ml |
| Placebo | Changes in Leptin | -0.2 ng/ml |
Secondary
Diastolic Blood Pressure
Time frame: 16 weeks after the beginning of each treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Diastolic Blood Pressure | -1.2 mm of mercury |
| Placebo | Diastolic Blood Pressure | -0.4 mm of mercury |
Secondary
HOMA Score
Time frame: 16 weeks from the start of each treatment period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | HOMA Score | 0.2 Ratio fasting glucose to insulin |
| Placebo | HOMA Score | 0.2 Ratio fasting glucose to insulin |
Secondary
REE
Resting Energy Expenditure
Time frame: 16 weeks from the start of each treatment period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | REE | -13.7 Kilocalories |
| Placebo | REE | 6.5 Kilocalories |
Secondary
Systolic Blood Pressure
Blood pressure was measured using a Dynamap automated monitoring device. The change is reported as the blood pressure measured at the beginning of the treatment group and after 16 weeks. We are reporting the change in the systolic blood presssure recorded.
Time frame: 16 weeks after the beginning of each treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Systolic Blood Pressure | -2.5 mm of mercury |
| Placebo | Systolic Blood Pressure | -1.3 mm of mercury |