Clinical trial NCT02160990: Effect of Exenatide in Obese Patients With Accelerated Gastric Emptying
Official title: Effect of Exenatide in Obese Patients With Accelerated Gastric Emptying
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Keywords: Obesity
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2014-06-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Gastric Emptying Half-time (T 1/2) of Solids
timeFrame: time frame is 30 days after the initiation of dose.
Secondary outcomes:
measure: Percentage of Gastric Contents Emptied at 1 Hour
timeFrame: Visit 4, approximately 1 hours after radiolabeled meal was ingested
measure: Change in Body Weight
timeFrame: baseline, day 30
measure: Satiation Expressed as Volume to Fullness
timeFrame: Visit 3, approximately 30 minutes after liquid meal
measure: Maximum Tolerated Volume
timeFrame: Visit 3, approximately 30 minutes after liquid meal
measure: Buffet Meal Intake (kcal)
timeFrame: Visit 4, approximately 30 minutes after start of "all you can eat" meal
measure: Aggregate Satiation Symptom Score
timeFrame: Visit 3, approximately 30 min after ingestion of nutrient drink test
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Acosta A, Camilleri M, Burton D, O'Neill J, Eckert D, Carlson P, Zinsmeister AR. Exenatide in obesity with accelerated gastric emptying: a randomized, pharmacodynamics study. Physiol Rep. 2015 Nov;3(11):e12610. doi: 10.14814/phy2.12610.