Exenatide Weekly Injections as an Adjunctive Treatment in Patients With Schizophrenia

The specific aims include:

Primary aim:

• 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:

• 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:

• Examine exenatide's effect on schizophrenia symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) total score.
• 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).
• Examine exenatide's effect on neuro-protection as measured by the change in hippocampal volume.
• 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).
• 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.
• 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.
• Examine the efficacy of exenatide in reducing body weight and improving glucose metabolism as measured by fasting plasma glucose and HbA1c.
• Examine the safety and tolerability of exenatide as measured by changes in the side effects questionnaire (SEQ, SEQabbrev), EKG and vital signs

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