Schizoaffective Disorder, Schizophrenia
Conditions
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
Interventions
DRUGExenatide
Exenatide SQ 2mg/week for 24 weeks.
DRUGPlacebo
Placebo SQ 1x/week for 24 weeks.
Sponsors
Stanley Medical Research Institute
University of Massachusetts, Worcester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Experimental (existing treatment) + (Drug)
Intervention:
Drug: Exenatide
Exenatide: Exenatide IM 2mg/week for 24 weeks. | 35 |
| Placebo (existing treatment) + (Placebo)
Intervention:
Drug: Placebo
Placebo: Placebo IM for 24 weeks. | 35 |
| Total | 70 |
Baseline characteristics
| Characteristic | Total | Experimental | Placebo |
|---|---|---|---|
| Age, Continuous | 42.7 years STANDARD_DEVIATION 12 | 41.6 years STANDARD_DEVIATION 12.3 | 43.9 years STANDARD_DEVIATION 11.9 |
| Age of illness onset | 24.2 years STANDARD_DEVIATION 8.8 | 23.7 years STANDARD_DEVIATION 8.3 | 24.6 years STANDARD_DEVIATION 9.3 |
| Atypical antipsychotic medication No | 13 Participants | 8 Participants | 5 Participants |
| Atypical antipsychotic medication Yes | 57 Participants | 27 Participants | 30 Participants |
| Duration of illness | 18.5 years STANDARD_DEVIATION 11.2 | 18.1 years STANDARD_DEVIATION 12.2 | 18.9 years STANDARD_DEVIATION 10.1 |
| Education | 12.8 years STANDARD_DEVIATION 2.3 | 12.9 years STANDARD_DEVIATION 2.4 | 12.7 years STANDARD_DEVIATION 2.1 |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 10 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Mixed | 4 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown/Not reported | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 52 Participants | 26 Participants | 26 Participants |
| Region of Enrollment United States | 70 Participants | 35 Participants | 35 Participants |
| Schizoaffective disorder | 33 Participants | 16 Participants | 17 Participants |
| Schizophrenia | 37 Participants | 19 Participants | 18 Participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Male | 55 Participants | 26 Participants | 29 Participants |
| Typical antipsychotic medication No | 48 Participants | 26 Participants | 22 Participants |
| Typical antipsychotic medication Yes | 22 Participants | 9 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 29 / 35 | 27 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
Primary
Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Week 24 | 35.2 score on a scale | Standard Deviation 13.3 |
| Experimental | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Baseline | 33.1 score on a scale | Standard Deviation 12.9 |
| Experimental | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Week 6 | 34.1 score on a scale | Standard Deviation 2.3 |
| Experimental | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Week 12 | 35.8 score on a scale | Standard Deviation 13 |
| Experimental | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Week 18 | 36.1 score on a scale | Standard Deviation 11.9 |
| Placebo | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Week 18 | 35.2 score on a scale | Standard Deviation 10.2 |
| Placebo | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Week 12 | 34.5 score on a scale | Standard Deviation 11.5 |
| Placebo | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Baseline | 34.1 score on a scale | Standard Deviation 15 |
| Placebo | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Week 24 | 35.0 score on a scale | Standard Deviation 11.1 |
| Placebo | Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score | Week 6 | 32.8 score on a scale | Standard Deviation 11.8 |
Secondary
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Week 6 | 27.3 score on a scale | Standard Deviation 17.3 |
| Experimental | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Week 18 | 28.7 score on a scale | Standard Deviation 18.1 |
| Experimental | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Week 12 | 28.4 score on a scale | Standard Deviation 17.3 |
| Experimental | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Week 24 | 31.2 score on a scale | Standard Deviation 16.5 |
| Experimental | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Baseline | 26.9 score on a scale | Standard Deviation 17.2 |
| Placebo | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Week 24 | 33.9 score on a scale | Standard Deviation 14.4 |
| Placebo | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Baseline | 24.7 score on a scale | Standard Deviation 12.6 |
| Placebo | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Week 6 | 27.2 score on a scale | Standard Deviation 15.4 |
| Placebo | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Week 12 | 28.1 score on a scale | Standard Deviation 16.2 |
| Placebo | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite T-score | Week 18 | 32.2 score on a scale | Standard Deviation 15.1 |