Exenatide for the Treatment of Weight Gain Associated With Olanzapine in Obese Adults
Condition: Weight Gain
MeSH terms: Body Weight; Weight Gain
Intervention: Exenatide; Placebo
Intervention description: The dosage of study medication will be 5 mcg injection of exenatide twice daily for 28 days. On day 28 the dosage may be increased, as tolerated, to 10 mcg twice daily.; Placebo: Sterile solution in equivalent doses as Exenatide
Intervention MeSH terms: Exenatide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: weight gain

Summary:

      The purpose of this research study is to test the safety and efficacy (how well it works) of
      exenatide as a treatment for weight gain associated with olanzapine in obese adults with
      Bipolar Disorder, Major Depressive Disorder, Schizophrenia or Schizoaffective Disorder

      Exenatide has been approved by the FDA for the treatment of Type 2 diabetes.

      It has not been approved for the treatment of weight gain associated with olanzapine in obese
      adults with bipolar disorder, Major Depressive Disorder, Schizophrenia or Schizoaffective
      Disorder
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects must be between the ages of 18 and 55 years old.

          2. Subjects must have bipolar I disorder, schizophrenia, schizoaffective disorder or MDD
             as defined by DSM-IV-TR criteria and diagnosed using the Structured Clinical Interview
             for DSM-IV (SCID).

          3. Subjects must have a Young Mania Rating Scale (YMRS) score < 16 and a
             Montgomery-Asberg Depression Rating Scale (MADRS) score < 24 at screening and baseline
             visits.

          4. Subjects must have the Scale for the Assessment of Positive Symptoms (SAPS) scores <2
             on all subscales.

          5. Subjects must have gained > 7% of their body weight following treatment with
             olanzapine as either documented in their medical records or by patient report.

          6. Subjects must be obese, as defined by a current Body Mass Index (BMI) > 30 kg/m2.

          7. Subjects must sign the Informed Consent Document after the nature of the trial has
             been fully explained.

          8. If female, subjects must be: postmenopausal, surgically incapable of childbearing, or
             practicing medically acceptable method(s) of contraception (e.g., hormonal methods,
             intrauterine device, abstinence) for at least one month prior to study entry and
             throughout the study.

          9. Subjects must be on a stable dose of olanzapine for at least 14 days and must have
             been on 5-30mg/day for at least 1 month.

        Major Exclusion Criteria

          1. Subjects with clinically significant suicidal or homicidal ideation.

          2. Subjects who have a DSM-IV lifetime diagnosis of a substance dependence disorder
             within the past 6 months or within the past month have been diagnosed with a substance
             abuse disorder, (except for nicotine abuse or dependence), as determined by
             psychiatric history or SCID interview.

          3. Subjects with a clinically significant or unstable medical disease, including hepatic,
             renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic,
             hematologic or other systemic medical conditions, that could interfere with diagnosis,
             assessment, or treatment of bipolar disorder or obesity, as well as subjects with a
             history of pancreatitis.

          4. Patients with clinically significant laboratory abnormalities (> 3 times upper limit
             of normal), on any of the following tests: CBC with differential, electrolytes, BUN,
             creatinine, hepatic transaminases, lipid profile, fasting glucose, urinalysis, or
             thyroid indices or clinically abnormal ECG.

          5. Female patients who are either pregnant or lactating.

          6. Any female patient whose sexual activity is unknown or in questions.

          7. Any history of current or past diabetes that has been treated with pharmacological
             intervention. Subjects who have a diagnosis of diabetes, are currently receiving
             exenatide, insulin, or an oral anti-hyperglycemic medication, or who have a nonfasting
             blood glucose ≥ 200 mg/dl or a fasting blood glucose ≥126 mg/dl on 2 separate tests.
             Subjects with pre-diabetes will not be excluded.

          8. Neurological disorders including epilepsy, stroke, or severe head trauma. Mental
             retardation (IQ <70).

        10. Treatment with an injectable depot neuroleptic within less than one dosing interval
        between depot neuroleptic injections and day 0.

        11. Treatment with concurrent mood stabilizers (except lithium), anticonvulsants, or
        antipsychotics.

        12. Other psychotic disorders (including delusional disorder, brief psychotic disorder,
        psychotic disorder due to a general medical condition, substance-induced psychotic
        disorder, psychotic disorder not otherwise specified) as defined in the DSM-IV.

        13. Dysthymic disorder or depressive disorder not otherwise specified, bipolar disorder not
        otherwise specified.

        14. Subjects previously enrolled in this study or have previously been treated with
        exenatide.

        15. Subjects who have received an experimental drug within 30 days. 16. Subjects who are
        displaying current clinically significant depressive or manic symptoms, defined as a MADRS
        score >24 or a YMRS score > 16 or who currently meet DSM-IV-TR criteria for a manic, mixed,
        hypomanic, or depressive episode.

        17. Subjects who are displaying current clinically significant psychotic symptoms, defined
        as any SAPS subscale score > 2 18. Subjects with a history of pancreatitis in themselves or
        any risk factors for developing pancreatitis (risk factors include but are not limited to:
        alcohol use, history of gallbladder disease or gallstones, diabetes or a family history of
        pancreatitis) 19. Subjects with elevated amylase or lipase levels as measured at the
        screening visit