Effect of Exenatide in Obese Patients With Accelerated Gastric Emptying

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02160990
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Exenatide; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Exenatide in Obese Patients With Accelerated Gastric Emptying
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Drug: Exenatide; 5 mcg exenatide subcutaneously twice daily for 30 days; Other Names: Byetta
Placebo Comparator: Placebo Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.	Drug: Placebo; placebo subcutaneously twice daily for 30 days

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. Change in Body Weight [baseline, day 30]

3. 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.

4. 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.

5. 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.

6. 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."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Michael Camilleri, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Camilleri, Primary Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02160990
• Other Study ID Numbers: 14-002683 Exenatide; R01DK067071; UL1TR000135
• First Posted: Jun 11, 2014
• Last Update Posted: Aug 9, 2016
• Last Verified: Jun 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Michael Camilleri, Primary Investigator, Mayo Clinic: Obesity
• Additional relevant MeSH terms: Obesity; Exenatide

Study Results

Participant Flow

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.
Period Title: Overall Study
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Exenatide	Placebo	Total
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.	Total of all reporting groups
Overall Participants	10	10	20
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	34	42.5	39.3
Sex: Female, Male (Count of Participants)
Female	6 60%	7 70%	13 65%
Male	4 40%	3 30%	7 35%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Gastric Emptying Half-time (T 1/2) of Solids
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.
Measure Participants	10	10
Median (Inter-Quartile Range) [minutes]	187	86

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Percentage of Gastric Contents Emptied at 1 Hour
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.
Measure Participants	10	10
Median (Inter-Quartile Range) [percentage of meal emptied]	12.4	38.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Change in Body Weight
Time Frame	baseline, day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.
Measure Participants	10	10
Median (Inter-Quartile Range) [kg]	-0.95	-0.55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Satiation Expressed as Volume to Fullness
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.
Measure Participants	10	10
Median (Inter-Quartile Range) [mL]	705	675

5. Secondary Outcome

Title	Maximum Tolerated Volume
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.
Measure Participants	10	10
Median (Inter-Quartile Range) [mL]	1244	1052

6. Secondary Outcome

Title	Buffet Meal Intake (kcal)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.
Measure Participants	10	10
Median (Inter-Quartile Range) [kcal]	977	1110

7. Secondary Outcome

Title	Aggregate Satiation Symptom Score
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.	Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.
Measure Participants	10	10
Median (Inter-Quartile Range) [mm]	145	172

Adverse Events

Time Frame	30 days
Arm/Group Title	Exenatide		Placebo
Arm/Group Description	Participants randomized to this arm received 5 mcg exenatide subcutaneously twice daily for 30 days.		Participants randomized to this arm received placebo subcutaneously twice daily for 30 days.
All Cause Mortality
	Exenatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Exenatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Exenatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.