Exenatide Weekly Injections as an Adjunctive Treatment in Patients With Schizophrenia

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 Heinrichs 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

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