Obesity
Conditions
Keywords
Obesity
Brief summary
The overall goal of this study was to determine the effect of exenatide on gastric emptying, satiety and satiation in obese participants. The hypothesis in this study was that exenatide retards gastric emptying in obese patients with baseline accelerated gastric emptying.
Detailed description
This study evaluated the effect of exenatide 5mcg subcutaneous (SQ) twice daily for 30-days versus placebo on gastric emptying, satiety, satiation and weight loss in obese participants with documented accelerated gastric emptying of solids. Visit 1: Screening - physical exam, questionnaires, pregnancy test. Participants were instructed to continue on the same diet and exercise routine during the entire study. Visit 2: Satiation Study Day - Subjects returned to the clinic after after fasting for at least 8 hours. A baseline satiation/nutrient drink test was performed on Day 0 prior to initiation of exenatide or placebo. The satiation/nutrient drink test involved drinking a liquid meal (Ensure) at a rate of one ounce per minute until no more could be ingested. At the same time, subject's symptoms were recorded while they drank the liquid meal and for 30 minutes after they reached the maximum volume tolerated. Subjects were randomized to exenatide or placebo, then received 30 days' supply of blinded study medication. Visit 3: Satiation Study Day - (This test was performed in the last 5 days of the 30 days of medication administration.) Subjects returned to the clinic after after fasting for at least 8 hours. Subjects were instructed to inject exenatide or placebo 30 minutes before the start of the satiation/nutrient drink test. The satiation/nutrient drink test was repeated. Visit 4: Gastric Emptying by Scintigraphy Day - (This test was performed in the last 5 days of the 30 days of medication administration.) Subjects returned to the clinic after after fasting for at least 8 hours. Subjects were instructed to inject exenatide or placebo 30 minutes before the start of the gastric emptying test. Subjects were given a scrambled egg breakfast with toast and a glass of milk. The eggs contain a small amount of radioactive substance. At the completion of the breakfast test meal, subjects were instructed to stand in front of a special camera and pictures were taken at specific intervals. On the same day, subjects participated in an all you can eat meal. This meal consists of lasagna, pudding, and skim milk. Food containers were weighed after the meal and calories consumed were estimated using validated dietary software.
Interventions
DRUGExenatide
5 mcg exenatide subcutaneously twice daily for 30 days
DRUGPlacebo
placebo subcutaneously twice daily for 30 days
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Obese subjects with BMI\> 30 Kg/m\^2: Otherwise healthy individuals who are not currently on treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, endocrine (other than hyperglycemia not requiring medical therapy) and unstable psychiatric disease. * Women of childbearing potential will have negative pregnancy test before initiation of medication. * Gastric emptying (GE): Accelerated GE T1/2 \< 79 minutes or GE 1h\>35 %
Exclusion criteria
* Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes Association criteria * Unstable heart disease as evidenced by ongoing angina * Congestive heart failure * Concomitant use of appetite suppressants (i.e., caffeine based or diethylpropion) or orlistat (Xenical®) * Uncontrolled hypertension (Blood pressure greater than 160/90 mmHg) * Use of anti-diabetic drugs including metformin, * History of nephrolithiasis, * Recurrent major depression, presence or history of suicidal behavior or ideation with intent to act, and current substantial depressive symptoms (Patient Health Questionnaire (PHQ-9) total score ≥10). * Gastroparesis * Inflammatory bowel disease or irritable bowel syndrome * Malignancy treated with chemotherapy within the past 3 years * History of pancreatitis * Renal insufficiency (eGFR less than 50 ml/min) * Concomitant use of monoamine oxidase inhibitors (i.e., phenelzine, selegiline), serotonergic agents, and other centrally acting appetite suppressants * Significant psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Scale (HADS) self-administered alcoholism screening test (SAAST, substance abuse) and the questionnaire on eating and weight patterns (binge eating disorders and bulimia). If such a dysfunction is identified by a HADS score ≥11 in any of the subscales or difficulties with substance or eating disorders, the participant will be excluded and given a referral letter to his/her primary care doctor for further appraisal and follow-up. * Intake of medication that could interfere with the interpretation of the study or cause drug interaction (i.e., ketoconazole, erythromycin). Specifically, birth control pill, estrogen replacement therapy, and thyroxine replacement are permissible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastric Emptying Half-time (T 1/2) of Solids | time frame is 30 days after the initiation of dose. | Gastric emptying of solids half-time is defined as the time for half of the ingested solids to leave the stomach. Subjects were given a scrambled egg breakfast with toast and a glass of milk. The eggs contained a small amount of a radioactive substance. Anterior and posterior gamma camera images were obtain immediately after radiolabeled meal ingestion, every 15 minutes for the first 2 hours, then 30 minutes for the next 2 hours (total 4 hours after the radiolabeled meal). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | baseline, day 30 | — |
| Satiation Expressed as Volume to Fullness | Visit 3, approximately 30 minutes after liquid meal | In the last 5 days of medication administration, subjects did a satiation/nutrient drink test. Participants recorded their sensations every 5 minutes using a visual analog scale (VAS) from 0-5, with level 0 being no symptoms, level 3 corresponding to fullness sensation after a typical meal, and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation). This measure was the volume consumed when the fullness sensation reached level 3. |
| Percentage of Gastric Contents Emptied at 1 Hour | Visit 4, approximately 1 hours after radiolabeled meal was ingested | Subjects were given a scrambled egg breakfast with toast and a glass of milk. The eggs contained a small amount of a radioactive substance. At the completion of the meal, subjects stood in front of a special camera and pictures were taken at specific intervals. This outcome measure is the proportion of the radiolabeled meal emptied at 1 hour. |
| Buffet Meal Intake (kcal) | Visit 4, approximately 30 minutes after start of all you can eat meal | Five hours after the standard egg meal ingested to measure gastric emptying, subjects were invited to eat, over a 30 minute period, a standard all you can eat meal. This meal consisted of either meat or vegetable lasagna, vanilla pudding, and skim milk. Personnel from the study team weighed the food servings post-meal and reported the amount of food left from single portions partially consumed. The total kcal of the food consumed was analyzed by using validated software. |
| Aggregate Satiation Symptom Score | Visit 3, approximately 30 min after ingestion of nutrient drink test | Postprandial fullness, nausea, bloating, and pain were measured 30 minutes after the liquid meal using 100 mm horizontal visual analog scales (VAS). The subscale scores could each range from none(0) to worst ever (100) at the left and right ends of the lines for each symptom. These satiation symptom scores (postprandial fullness, nausea, bloating, and pain) were combined to generate a total scale score with a different total scale range (0 - 400 mm) with 0 mm indicating none and 400 indicating worst ever. |
| Maximum Tolerated Volume | Visit 3, approximately 30 minutes after liquid meal | In the last 5 days of medication administration, subjects did a satiation/nutrient drink test. Participants recorded their sensations every 5 minutes using a visual analog scale (VAS) from 0-5, with level 0 being no symptoms, level 3 corresponding to fullness sensation after a typical meal, and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation). This measure was the volume consumed when the fullness sensation reached level 5. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days. | 10 |
| Placebo Participants randomized to this arm received placebo subcutaneously twice daily for 30 days. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Exenatide | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34 years | 42.5 years | 39.3 years |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Gastric Emptying Half-time (T 1/2) of Solids
Gastric emptying of solids half-time is defined as the time for half of the ingested solids to leave the stomach. Subjects were given a scrambled egg breakfast with toast and a glass of milk. The eggs contained a small amount of a radioactive substance. Anterior and posterior gamma camera images were obtain immediately after radiolabeled meal ingestion, every 15 minutes for the first 2 hours, then 30 minutes for the next 2 hours (total 4 hours after the radiolabeled meal).
Time frame: time frame is 30 days after the initiation of dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Gastric Emptying Half-time (T 1/2) of Solids | 187 minutes |
| Placebo | Gastric Emptying Half-time (T 1/2) of Solids | 86 minutes |
p-value: <0.001ANCOVA
Secondary
Aggregate Satiation Symptom Score
Postprandial fullness, nausea, bloating, and pain were measured 30 minutes after the liquid meal using 100 mm horizontal visual analog scales (VAS). The subscale scores could each range from none(0) to worst ever (100) at the left and right ends of the lines for each symptom. These satiation symptom scores (postprandial fullness, nausea, bloating, and pain) were combined to generate a total scale score with a different total scale range (0 - 400 mm) with 0 mm indicating none and 400 indicating worst ever.
Time frame: Visit 3, approximately 30 min after ingestion of nutrient drink test
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Aggregate Satiation Symptom Score | 145 mm |
| Placebo | Aggregate Satiation Symptom Score | 172 mm |
Secondary
Buffet Meal Intake (kcal)
Five hours after the standard egg meal ingested to measure gastric emptying, subjects were invited to eat, over a 30 minute period, a standard all you can eat meal. This meal consisted of either meat or vegetable lasagna, vanilla pudding, and skim milk. Personnel from the study team weighed the food servings post-meal and reported the amount of food left from single portions partially consumed. The total kcal of the food consumed was analyzed by using validated software.
Time frame: Visit 4, approximately 30 minutes after start of all you can eat meal
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Buffet Meal Intake (kcal) | 977 kcal |
| Placebo | Buffet Meal Intake (kcal) | 1110 kcal |
Secondary
Change in Body Weight
Time frame: baseline, day 30
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Change in Body Weight | -0.95 kg |
| Placebo | Change in Body Weight | -0.55 kg |
p-value: 0.23ANCOVA
Secondary
Maximum Tolerated Volume
In the last 5 days of medication administration, subjects did a satiation/nutrient drink test. Participants recorded their sensations every 5 minutes using a visual analog scale (VAS) from 0-5, with level 0 being no symptoms, level 3 corresponding to fullness sensation after a typical meal, and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation). This measure was the volume consumed when the fullness sensation reached level 5.
Time frame: Visit 3, approximately 30 minutes after liquid meal
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Maximum Tolerated Volume | 1244 mL |
| Placebo | Maximum Tolerated Volume | 1052 mL |
Secondary
Percentage of Gastric Contents Emptied at 1 Hour
Subjects were given a scrambled egg breakfast with toast and a glass of milk. The eggs contained a small amount of a radioactive substance. At the completion of the meal, subjects stood in front of a special camera and pictures were taken at specific intervals. This outcome measure is the proportion of the radiolabeled meal emptied at 1 hour.
Time frame: Visit 4, approximately 1 hours after radiolabeled meal was ingested
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Percentage of Gastric Contents Emptied at 1 Hour | 12.4 percentage of meal emptied |
| Placebo | Percentage of Gastric Contents Emptied at 1 Hour | 38.2 percentage of meal emptied |
p-value: <0.001ANCOVA
Secondary
Satiation Expressed as Volume to Fullness
In the last 5 days of medication administration, subjects did a satiation/nutrient drink test. Participants recorded their sensations every 5 minutes using a visual analog scale (VAS) from 0-5, with level 0 being no symptoms, level 3 corresponding to fullness sensation after a typical meal, and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation). This measure was the volume consumed when the fullness sensation reached level 3.
Time frame: Visit 3, approximately 30 minutes after liquid meal
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Satiation Expressed as Volume to Fullness | 705 mL |
| Placebo | Satiation Expressed as Volume to Fullness | 675 mL |