Exenatide for the Treatment of Weight Gain Associated With Olanzapine in Obese Adults

• Sponsor: University of Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT00845507
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 54
• Location: 1
• Arms: 2
• Duration (Months): 78.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this research study is to test the safety and efficacy (how well it works) of exenatide as a treatment for weight gain associated with olanzapine in obese adults with Bipolar Disorder, Major Depressive Disorder, Schizophrenia or Schizoaffective Disorder

Exenatide has been approved by the FDA for the treatment of Type 2 diabetes.

It has not been approved for the treatment of weight gain associated with olanzapine in obese adults with bipolar disorder, Major Depressive Disorder, Schizophrenia or Schizoaffective Disorder

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

Detailed Description

Double-blind studies suggest that olanzapine is highly effective for the treatment of individuals with bipolar disorder. However, weight gain and impaired glucose tolerance remain significant concerns associated with olanzapine. Exenatide is an anti-diabetic medication that is associated with weight loss and improved glucose regulation. Therefore, the overall goal of the proposed study is to conduct a 16-week double-blind placebo-controlled study of exenatide for the treatment of weight gain associated with olanzapine in 60 obese adults with bipolar disorder treated with olanzapine. We propose to conduct the study over the course of 24 months, with an expected enrollment of approximately 3 patients per month. The primary outcome measure will be change from baseline to endpoint in weight. The secondary outcome measures will include changes from baseline to endpoint, in body mass index (BMI), abdominal circumference, metabolic parameters, clinical global improvement of psychiatric symptoms, and change in manic, depressive and psychotic symptoms. Rates of adverse events also will be assessed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind Placebo-Controlled Study of Exenatide for the Treatment of Weight Gain Associated With Olanzapine in Obese Adults With Bipolar Disorder, Major Depressive Disorder, Schizophrenia or Schizoaffective Disorder
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide Group Exenatide dstarted at 5 mcg subcutaneously twice daily within one hour before the morning and evening meals, and increased (as tolerated) to 10 mcg.	Drug: Exenatide; The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.; Other Names: Exenatide (Byeta)
Placebo Comparator: Placebo Group Placebo: Sterile solution in equivalent doses as Exenatide	Drug: Placebo; Placebo: Sterile solution in equivalent doses as Exenatide

Outcome Measures

Primary Outcome Measures

1. Change in Weight From Baseline to Endpoint. [16 Weeks]

   Change in weight from baseline to endpoint in the intent-to-treat (ITT) population (all subjects who took at least one dose of study medication and had one post-baseline evaluation).

Secondary Outcome Measures

1. Change in Body Mass Index (BMI) From Baseline to Endpoint. [16 Weeks]

   Secondary outcome measures included change in body mass index (BMI).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects must be between the ages of 18 and 55 years old.

2. Subjects must have bipolar I disorder, schizophrenia, schizoaffective disorder or MDD as defined by DSM-IV-TR criteria and diagnosed using the Structured Clinical Interview for DSM-IV (SCID).

3. Subjects must have a Young Mania Rating Scale (YMRS) score < 16 and a Montgomery-Asberg Depression Rating Scale (MADRS) score < 24 at screening and baseline visits.

4. Subjects must have the Scale for the Assessment of Positive Symptoms (SAPS) scores <2 on all subscales.

5. Subjects must have gained > 7% of their body weight following treatment with olanzapine as either documented in their medical records or by patient report.

6. Subjects must be obese, as defined by a current Body Mass Index (BMI) > 30 kg/m2.

7. Subjects must sign the Informed Consent Document after the nature of the trial has been fully explained.

8. If female, subjects must be: postmenopausal, surgically incapable of childbearing, or practicing medically acceptable method(s) of contraception (e.g., hormonal methods, intrauterine device, abstinence) for at least one month prior to study entry and throughout the study.

9. Subjects must be on a stable dose of olanzapine for at least 14 days and must have been on 5-30mg/day for at least 1 month.

Major Exclusion Criteria

1. Subjects with clinically significant suicidal or homicidal ideation.

2. Subjects who have a DSM-IV lifetime diagnosis of a substance dependence disorder within the past 6 months or within the past month have been diagnosed with a substance abuse disorder, (except for nicotine abuse or dependence), as determined by psychiatric history or SCID interview.

3. Subjects with a clinically significant or unstable medical disease, including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, hematologic or other systemic medical conditions, that could interfere with diagnosis, assessment, or treatment of bipolar disorder or obesity, as well as subjects with a history of pancreatitis.

4. Patients with clinically significant laboratory abnormalities (> 3 times upper limit of normal), on any of the following tests: CBC with differential, electrolytes, BUN, creatinine, hepatic transaminases, lipid profile, fasting glucose, urinalysis, or thyroid indices or clinically abnormal ECG.

5. Female patients who are either pregnant or lactating.

6. Any female patient whose sexual activity is unknown or in questions.

7. Any history of current or past diabetes that has been treated with pharmacological intervention. Subjects who have a diagnosis of diabetes, are currently receiving exenatide, insulin, or an oral anti-hyperglycemic medication, or who have a nonfasting blood glucose ≥ 200 mg/dl or a fasting blood glucose ≥126 mg/dl on 2 separate tests. Subjects with pre-diabetes will not be excluded.

8. Neurological disorders including epilepsy, stroke, or severe head trauma. Mental retardation (IQ <70).

9. Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections and day 0.

10. Treatment with concurrent mood stabilizers (except lithium), anticonvulsants, or antipsychotics.

11. Other psychotic disorders (including delusional disorder, brief psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, psychotic disorder not otherwise specified) as defined in the DSM-IV.

12. Dysthymic disorder or depressive disorder not otherwise specified, bipolar disorder not otherwise specified.

13. Subjects previously enrolled in this study or have previously been treated with exenatide.

14. Subjects who have received an experimental drug within 30 days. 16. Subjects who are displaying current clinically significant depressive or manic symptoms, defined as a MADRS score >24 or a YMRS score > 16 or who currently meet DSM-IV-TR criteria for a manic, mixed, hypomanic, or depressive episode.

15. Subjects who are displaying current clinically significant psychotic symptoms, defined as any SAPS subscale score > 2 18. Subjects with a history of pancreatitis in themselves or any risk factors for developing pancreatitis (risk factors include but are not limited to: alcohol use, history of gallbladder disease or gallstones, diabetes or a family history of pancreatitis) 19. Subjects with elevated amylase or lipase levels as measured at the screening visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Cincinnati	Cincinnati	Ohio	United States	45219

Sponsors and Collaborators

• University of Cincinnati
• Eli Lilly and Company

Investigators

• Principal Investigator: Melissa DelBello, MD, University of Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Melissa Delbello, Professor, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT00845507
• Other Study ID Numbers: Exenatide
• First Posted: Feb 18, 2009
• Last Update Posted: Apr 20, 2018
• Last Verified: Aug 1, 2015

• Keywords provided by Melissa Delbello, Professor, University of Cincinnati: weight gain
• Additional relevant MeSH terms: Body Weight; Weight Gain; Exenatide

Study Results

Participant Flow

Arm/Group Title	Exenatide Group	Placebo Group
Arm/Group Description	Exenatide dstarted at 5 mcg subcutaneously twice daily within one hour before the morning and evening meals, and increased (as tolerated) to 10 mcg. Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.	Placebo: Sterile solution in equivalent doses as Exenatide Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.
Period Title: Overall Study
STARTED	24	30
COMPLETED	22	29
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Exenatide Group	Placebo Group	Total
Arm/Group Description	Exenatide dstarted at 5 mcg subcutaneously twice daily within one hour before the morning and evening meals, and increased (as tolerated) to 10 mcg. Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.	Placebo: Sterile solution in equivalent doses as Exenatide Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.	Total of all reporting groups
Overall Participants	24	30	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.2 (9.3)	39.3 (11.7)	41.4 (10.9)
Sex: Female, Male (Count of Participants)
Female	15 62.5%	21 70%	36 66.7%
Male	9 37.5%	9 30%	18 33.3%
Race/Ethnicity, Customized (Count of Participants)
White	12 50%	18 60%	30 55.6%
Non-White	12 50%	12 40%	24 44.4%
Region of Enrollment (participants) [Number]
United States	24 100%	30 100%	54 100%
Weight (Pounds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Pounds]	197 (32)	209 (51)	204 (44)

Outcome Measures

1. Primary Outcome

Title	Change in Weight From Baseline to Endpoint.
Description	Change in weight from baseline to endpoint in the intent-to-treat (ITT) population (all subjects who took at least one dose of study medication and had one post-baseline evaluation).
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

All subjects who took at least one dose of study medication and had one post-baseline evaluation.

Arm/Group Title	Exenatide Group	Placebo Group
Arm/Group Description	Exenatide dstarted at 5 mcg subcutaneously twice daily within one hour before the morning and evening meals, and increased (as tolerated) to 10 mcg. Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.	Placebo: Sterile solution in equivalent doses as Exenatide Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.
Measure Participants	22	29
Mean (Standard Deviation) [Pounds]	-1.1 (6.2)	5.9 (10.3)

2. Secondary Outcome

Title	Change in Body Mass Index (BMI) From Baseline to Endpoint.
Description	Secondary outcome measures included change in body mass index (BMI).
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

All subjects who took at least one dose of study medication and had one post-baseline evaluation.

Arm/Group Title	Exenatide Group	Placebo Group
Arm/Group Description	Exenatide dstarted at 5 mcg subcutaneously twice daily within one hour before the morning and evening meals, and increased (as tolerated) to 10 mcg. Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.	Placebo: Sterile solution in equivalent doses as Exenatide Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.
Measure Participants	22	29
Mean (Standard Deviation) [Kgs/meter squared]	-0.2 (1.0)	1.0 (1.7)

Adverse Events

Time Frame	Up to 16 weeks
Arm/Group Title	Exenatide Group		Placebo Group
Arm/Group Description	Exenatide dstarted at 5 mcg subcutaneously twice daily within one hour before the morning and evening meals, and increased (as tolerated) to 10 mcg. Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.		Placebo: Sterile solution in equivalent doses as Exenatide Exenatide: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.
All Cause Mortality
	Exenatide Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Exenatide Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/24 (8.3%)		1/30 (3.3%)
Gastrointestinal disorders
Hospitalization for Mallory-Weiss tear	1/24 (4.2%)	1	0/30 (0%)	0
Psychiatric disorders
Hospitalization for exacerbation of depressive symptoms	1/24 (4.2%)	1	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Exenatide Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/24 (58.3%)		11/30 (36.7%)
Gastrointestinal disorders
Gastointestinal disturbance (includes acid reflux, constipation, diarrhea, heartburn, nausea etc)	14/24 (58.3%)	14	11/30 (36.7%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.