Exenatide Weekly Injections as an Adjunctive Treatment in Patients With Schizophrenia

• Sponsor: University of Massachusetts, Worcester (Other)
• Overall Status: Completed
• CT.gov ID: NCT02417142
• Collaborator: Stanley Medical Research Institute (Other)
• Enrollment: 70
• Location: 1
• Arms: 2
• Actual Duration (Months): 70
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This is a 24-week, randomized, double-blind, placebo-controlled trial of exenatide weekly injection (2mg per dose) as an adjunctive therapy in 70 schizophrenia subjects to examine exenatide's effects on negative symptoms and cognition.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder	Drug: Exenatide; Drug: Placebo	Phase 4

Detailed Description

The specific aims include:

Primary aim:

1. Examine the efficacy of exenatide weekly injection in improving negative symptoms as measured by the Scale for the Assessment of Negative Symptoms (SANS) total score.

Secondary aims:

1. Examine the efficacy of exenatide in improving cognition as measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) composite score.

Tertiary/Exploratory aims:

1. Examine exenatide's effect on schizophrenia symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) total score.

2. Examine the efficacy of exenatide in improving social function as measured by the Instrumental Activities of Daily Living Scale (IADL) and the Heinrich Carpenter Quality of Life Scale (QLS).

3. Examine exenatide's effect on neuro-protection as measured by the change in hippocampal volume.

4. Examine exenatide's effects on inflammatory markers including serum levels of high sensitivity C-reactive Protein (CRP), Interleukin 6 (IL-6), and tumor necrosis factor (TNF-α).

5. Examine the potential moderator role of baseline serum levels of C-reactive Protein (CRP), Interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and baseline hippocampal volume for exenatide's effects on negative and cognitive symptoms.

6. Examine the potential mediator role of changes from baseline in serum levels of C-reactive Protein (CRP), Interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and hippocampal volume for exenatide's effects on negative and cognitive symptoms.

7. Examine the efficacy of exenatide in reducing body weight and improving glucose metabolism as measured by fasting plasma glucose and HbA1c.

8. Examine the safety and tolerability of exenatide as measured by changes in the side effects questionnaire (SEQ, SEQabbrev), EKG and vital signs

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Exenatide Weekly Injections as an Adjunctive Treatment in Patients With Schizophrenia
• Actual Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Jul 1, 2019
• Actual Study Completion Date: Jul 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Exenatide 2mg subcutaneous injection, once weekly	Drug: Exenatide; Exenatide SQ 2mg/week for 24 weeks.; Other Names: Bydureon
Placebo Comparator: Placebo Placebo	Drug: Placebo; Placebo SQ 1x/week for 24 weeks.; Other Names: Control

Outcome Measures

Primary Outcome Measures

1. Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score [Baseline, Week 6, Week 12, Week 18 and Week 24]

   SANS measures negative symptoms on a 25-item, six point scale each (0-5; none-severe). Items are listed under five domains including affective flattening or blunting, alogia, avolition/apathy, anhedonia/asociality, and attention. The total possible score ranges from 0 to 125.

Secondary Outcome Measures

1. Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score [Baseline, Week 6, Week 12, Week 18, and Week 24.]

   The MATRICS Consensus Cognitive Battery (MCCB) measures cognition relevant to schizophrenia and related disorders. The MCCB consists of ten individually administered tests that measure cognitive performance in seven domains including speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The raw scores from the ten tests are entered in the MCCB Computer Scoring Program software, which provides an age and gender-corrected T-score and percentile on the seven cognitive domains. A T-score of 50 +/- 10 represents a normative mean performance in each test. Accordingly, the criterion for assignment to cognitively normal-range group require an overall composite T-score from 40 to 60. These data points from baseline visit to week 24 will measure changes in cognition in addition overall cognitive ability compared to healthy individuals.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• age 18-65 years

• diagnosis of schizophrenia or schizoaffective disorder

• stable dose of the current antipsychotic drug for at least one month

• well established compliance with outpatient treatment per treating clinician's judgment

• able to complete the cognitive assessment battery (must be English speaking)

• Female subjects will be eligible to participate in the study if they are of non-childbearing potential or of child-bearing potential and willing to practice appropriate birth control methods during the study

Exclusion Criteria:

• inability to provide informed consent

• current substance abuse

• psychiatrically unstable per treating clinician's judgment

• significant medical illnesses including uncontrolled hypertension, diabetes, seizure disorder, severe cardiovascular, cerebrovascular, pulmonary, or thyroid diseases

• currently on anti-inflammatory or immunosuppressant medication including oral steroids

• currently on sulfonylurea drugs (e.g. glyburide)

• history of chronic infection (including tuberculosis, HIV and hepatitis), malignancy, organ transplantation, blood dyscrasia, central nervous system demyelinating disorder, and any other known autoimmune or inflammatory condition

• pregnant or breastfeeding

• prisoners

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UMass Medical School	Worcester	Massachusetts	United States	01605

Sponsors and Collaborators

• University of Massachusetts, Worcester
• Stanley Medical Research Institute

Investigators

• Principal Investigator: Xiaoduo Fan, MD, MPH, MS, University of Massachusetts, Worcester

Study Documents (Full-Text)

• Study Protocol - Nov 30, 2019
• Statistical Analysis Plan - Nov 30, 2019

More Information

Publications

None provided.

• Responsible Party: Xiaoduo Fan, Xiaoduo Fan, MD, MPH, MS, University of Massachusetts, Worcester
• ClinicalTrials.gov Identifier: NCT02417142
• Other Study ID Numbers: 13T-005
• First Posted: Apr 15, 2015
• Last Update Posted: Jan 14, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Schizophrenia; Psychotic Disorders; Exenatide

Study Results

Participant Flow

Recruitment Details	Single-site study conducted at University of Massachusetts (UMass) Medical School. Subjects were recruited from UMass Memorial Healthcare facilities and ambulatory clinics in Worcester, MA.
Pre-assignment Detail	Subjects who met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) criteria for schizophrenia or schizoaffective disorder were enrolled in the study (see inclusion/exclusion criteria). Eligible subjects were randomly assigned to either the experimental or placebo group.

Arm/Group Title	Experimental	Placebo
Arm/Group Description	(existing treatment) + (Drug) Intervention: Drug: Exenatide Exenatide: Exenatide 2mg/week subcutaneous injection for 24 weeks.	(existing treatment) + (Placebo) Intervention: Drug: Placebo Placebo: Placebo IM for 24 weeks.
Period Title: Overall Study
STARTED	35	35
COMPLETED	19	22
NOT COMPLETED	16	13

Baseline Characteristics

Arm/Group Title	Experimental	Placebo	Total
Arm/Group Description	(existing treatment) + (Drug) Intervention: Drug: Exenatide Exenatide: Exenatide IM 2mg/week for 24 weeks.	(existing treatment) + (Placebo) Intervention: Drug: Placebo Placebo: Placebo IM for 24 weeks.	Total of all reporting groups
Overall Participants	35	35	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.6 (12.3)	43.9 (11.9)	42.7 (12.0)
Sex: Female, Male (Count of Participants)
Female	9 25.7%	6 17.1%	15 21.4%
Male	26 74.3%	29 82.9%	55 78.6%
Race/Ethnicity, Customized (Count of Participants)
White	26 74.3%	26 74.3%	52 74.3%
Black/African American	4 11.4%	6 17.1%	10 14.3%
Asian	2 5.7%	0 0%	2 2.9%
Mixed	1 2.9%	3 8.6%	4 5.7%
Unknown/Not reported	2 5.7%	0 0%	2 2.9%
Region of Enrollment (Count of Participants)
United States	35 100%	35 100%	70 100%
Education (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.9 (2.4)	12.7 (2.1)	12.8 (2.3)
Age of illness onset (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	23.7 (8.3)	24.6 (9.3)	24.2 (8.8)
Duration of illness (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	18.1 (12.2)	18.9 (10.1)	18.5 (11.2)
Schizophrenia (Count of Participants)
Count of Participants [Participants]	19 54.3%	18 51.4%	37 52.9%
Schizoaffective disorder (Count of Participants)
Count of Participants [Participants]	16 45.7%	17 48.6%	33 47.1%
Typical antipsychotic medication (Count of Participants)
Yes	9 25.7%	13 37.1%	22 31.4%
No	26 74.3%	22 62.9%	48 68.6%
Atypical antipsychotic medication (Count of Participants)
Yes	27 77.1%	30 85.7%	57 81.4%
No	8 22.9%	5 14.3%	13 18.6%

Outcome Measures

1. Primary Outcome

Title	Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score
Description	SANS measures negative symptoms on a 25-item, six point scale each (0-5; none-severe). Items are listed under five domains including affective flattening or blunting, alogia, avolition/apathy, anhedonia/asociality, and attention. The total possible score ranges from 0 to 125.
Time Frame	Baseline, Week 6, Week 12, Week 18 and Week 24

Outcome Measure Data

Analysis Population Description

12 subjects in experimental arm withdrew or were lost to follow-up by week 24. 4 subjects in the experimental arm were removed from study by investigator by week 24. 11 subjects in placebo arm withdrew or were lost to follow-up by week 24. 2 subjects in the placebo arm were removed from study by investigator by week 24. Reasons for removal include inpatient hospitalization, increase in depressive symptoms, elevated HbA1c, starting insulin therapy and repeatedly missing visits.

Arm/Group Title	Experimental	Placebo
Arm/Group Description	(existing treatment) + (Drug) Intervention: Drug: Exenatide Exenatide: Exenatide IM 2mg/week for 24 weeks.	(existing treatment) + (Placebo) Intervention: Drug: Placebo Placebo: Placebo IM for 24 weeks.
Measure Participants	35	35
Baseline	33.1 (12.9)	34.1 (15.0)
Week 6	34.1 (2.3)	32.8 (11.8)
Week 12	35.8 (13.0)	34.5 (11.5)
Week 18	36.1 (11.9)	35.2 (10.2)
Week 24	35.2 (13.3)	35.0 (11.1)

2. Secondary Outcome

Title	Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score
Description	The MATRICS Consensus Cognitive Battery (MCCB) measures cognition relevant to schizophrenia and related disorders. The MCCB consists of ten individually administered tests that measure cognitive performance in seven domains including speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The raw scores from the ten tests are entered in the MCCB Computer Scoring Program software, which provides an age and gender-corrected T-score and percentile on the seven cognitive domains. A T-score of 50 +/- 10 represents a normative mean performance in each test. Accordingly, the criterion for assignment to cognitively normal-range group require an overall composite T-score from 40 to 60. These data points from baseline visit to week 24 will measure changes in cognition in addition overall cognitive ability compared to healthy individuals.
Time Frame	Baseline, Week 6, Week 12, Week 18, and Week 24.

Outcome Measure Data

Analysis Population Description

12 subjects in experimental arm withdrew or were lost to follow-up by week 24. 4 subjects in the experimental arm were removed from study by investigator by week 24. 11 subjects in placebo arm withdrew or were lost to follow-up by week 24. 2 subjects in the placebo arm were removed from study by investigator by week 24. Reasons for removal include inpatient hospitalization, increase in depressive symptoms, elevated HbA1c, starting insulin and repeatedly missing visits during study period.

Arm/Group Title	Experimental	Placebo
Arm/Group Description	(existing treatment) + (Drug) Intervention: Drug: Exenatide Exenatide: Exenatide IM 2mg/week for 24 weeks.	(existing treatment) + (Placebo) Intervention: Drug: Placebo Placebo: Placebo IM for 24 weeks.
Measure Participants	35	35
Baseline	26.9 (17.2)	24.7 (12.6)
Week 6	27.3 (17.3)	27.2 (15.4)
Week 12	28.4 (17.3)	28.1 (16.2)
Week 18	28.7 (18.1)	32.2 (15.1)
Week 24	31.2 (16.5)	33.9 (14.4)

Adverse Events

Time Frame	24 weeks
Arm/Group Title	Experimental		Placebo
Arm/Group Description	(existing treatment) + (Drug) Intervention: Drug: Exenatide Exenatide: Exenatide IM 2mg/week for 24 weeks.		(existing treatment) + (Placebo) Intervention: Drug: Placebo Placebo: Placebo IM for 24 weeks.
All Cause Mortality
	Experimental		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Serious Adverse Events
	Experimental		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	Experimental		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/35 (82.9%)		27/35 (77.1%)
Cardiac disorders
Chest pain	3/35 (8.6%)		0/35 (0%)
Eye disorders
Blurry vision	2/35 (5.7%)		0/35 (0%)
Gastrointestinal disorders
Heartburn	5/35 (14.3%)		8/35 (22.9%)
Constipation	5/35 (14.3%)		8/35 (22.9%)
Vomiting	2/35 (5.7%)		6/35 (17.1%)
Diarrhea	3/35 (8.6%)		3/35 (8.6%)
Abdominal pain	3/35 (8.6%)		1/35 (2.9%)
Indigestion	3/35 (8.6%)		1/35 (2.9%)
General disorders
Headache	9/35 (25.7%)		10/35 (28.6%)
Nausea	4/35 (11.4%)		2/35 (5.7%)
Dizziness	3/35 (8.6%)		3/35 (8.6%)
Fatigue	3/35 (8.6%)		2/35 (5.7%)
Hunger	2/35 (5.7%)		2/35 (5.7%)
Decreased appetite	2/35 (5.7%)		1/35 (2.9%)
Sedation	2/35 (5.7%)		1/35 (2.9%)
Psychiatric disorders
Irritability/anxiety	7/35 (20%)		3/35 (8.6%)
Suicidal Ideation	2/35 (5.7%)		3/35 (8.6%)
Skin and subcutaneous tissue disorders
Bump at injection site	17/35 (48.6%)		0/35 (0%)
Itchiness at injection site	8/35 (22.9%)		0/35 (0%)

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.