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Exenatide Weekly Injections as an Adjunctive Treatment in Patients With Schizophrenia

Phase 4
Completed
Conditions
Schizoaffective Disorder
Schizophrenia
Interventions
Drug: Placebo
Registration Number
NCT02417142
Lead Sponsor
University of Massachusetts, Worcester
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.

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
70
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo
ExperimentalExenatideExenatide 2mg subcutaneous injection, once weekly
Primary Outcome Measures
NameTimeMethod
Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total ScoreBaseline, 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
NameTimeMethod
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-scoreBaseline, 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.

Trial Locations

Locations (1)

UMass Medical School

🇺🇸

Worcester, Massachusetts, United States

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