The Effects of Rimonabant, on Weight and Metabolic Risk Factors
Condition: Schizophrenia; Schizoaffective Disorder; Obesity; Hypertension; Smoking
MeSH terms: Schizophrenia; Psychotic Disorders
Intervention: Rimonabant; Placebo
Intervention description: One 20 mg tablet given 1 time per day for 112 days.; One placebo tablet given 1 time per day for 112 days.
Intervention MeSH terms: Rimonabant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Metabolic abnormalities; Safety; Satiety

Summary:

      1) To examine the efficacy of rimonabant in decreasing weight and metabolic
      parameters/cardiovascular disease risk in people with schizophrenia receiving second
      generation antipsychotics 2) To examine the safety and tolerability of rimonabant as an
      adjunctive agent for decreasing weight and metabolic risk in people with schizophrenia 3) To
      examine the efficacy of rimonabant for neurocognitive impairments in people with
      schizophrenia treated with second-generation antipsychotics (secondary outcome) 4) To examine
      the efficacy of rimonabant for patient perceived health outcomes and quality of life
      (secondary outcome) 5) To test the effect of rimonabant on cigarette smoking, nicotine
      dependence and nicotine craving in people with schizophrenia 6) To examine the effects of
      rimonabant on food satiety in people with schizophrenia

      There is an increasing awareness of the problem of metabolic issues in people with
      schizophrenia and renewed focus on physical health care for this population. There is
      under-treatment, in general, of medical conditions in people with schizophrenia, and
      increased mortality from natural causes. People with schizophrenia are at risk for developing
      obesity due to many factors including inactive lifestyle, poor dietary choices, and side
      effects of the commonly used atypical antipsychotics. Metabolic syndrome has been discussed
      in the cardiology and endocrinology for over two decades, but its prevalence in the mentally
      ill is only now being fully realized. Diabetes mellitus may be twice as prevalent among
      patients with schizophrenia as in the general population and metabolic syndrome is probably
      even more prevalent than diabetes among people with schizophrenia. There is now an
      opportunity to address this serious problem. A new drug, rimonabant, has recently been
      approved in several European and Latin American countries. This drug represents the first of
      a new class of psychoactive drugs witch may improve metabolic problems through decreasing
      appetite drive. This may also help decrease the drive for cigarette use, which is also a
      great problem for people with schizophrenia. Is this a safe and effective treatment in this
      population? This study proposes to test this question in a rapid study, which will develop
      the basis for future work in this important area.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Any gender

          2. Any race,

          3. Age range of 18-55.

          4. Meet DSM-IV (APA, 1994) criteria for either schizophrenia or schizoaffective disorder.

          5. Have a BMI greater than or equal to 27 with treated or untreated hyperlipidemia/
             hypertriglyceridemia or a BMI greater than or equal to 30 regardless of concurrent
             risk factors

          6. Be treated with the same SGA for at least 8 weeks and to have received a constant
             therapeutic dose for at least 30 days

          7. Be clinically stable (for inpatients: at least one month post admission).
             Hyperlipidemia and hypertriglyceridemia are defined by ATP III guidelines such that
             borderline high and high will be considered as criteria for these disorders (ATP III
             2001).

        Exclusion Criteria:

          1. Subjects with significant recent depressive symptoms will be excluded from the study,
             defined as any history of a suicide attempt or suicidal ideation or hospitalization
             for depressive symptoms within the last 6 months; or a high level of current
             depressive symptoms (Calgary Depression Scale of > 7) (Addington 1993, Kim et al
             2006).

          2. Subjects with intermittent alcohol or substance use will not be excluded unless they
             have met DSM-IV criteria for current alcohol or substance dependence within the last 6
             months or DSM-IV criteria for alcohol or substance abuse within the last month.

          3. Subjects with nicotine use or dependence will not be excluded.

          4. Subjects with daily marijuana use will be excluded because of the possibility of
             physical dependence on cannabis. Those with with marijuana use no more than once a
             week will not be excluded because such subjects will not be physically dependent on
             marijuana and so not at risk for rimonabant-elicited acute cannabis withdrawal.
             Experimental studies of human cannabis physical dependence and withdrawal suggest that
             high-dose, multiple times a day administration is needed to produce physical
             dependence (Jones et al., 1976; Haney et al., 1999)

          5. Subjects with a history of Crohn's Disease or Irritable Bowel Syndrome

          6. Subjects with a organic brain disorder

          7. A DSM-IV eating disorder

          8. Subjects with mental retardation will be excluded to exclude subjects with cognitive
             impairment not related to schizophrenia. Mental retardation will be determined by
             chart review for a mental retardation diagnosis or a history of an IQ <70 and
             functional disability noted before the age of 18 (DSM-IV criteria for mental
             retardation).

          9. Subjects with a medical condition, whose pathology or treatment could alter the
             presentation or treatment of schizophrenia or significantly increase the risk
             associated with the proposed treatment protocol will be excluded.

         10. Subjects with a history of surgical procedures for weight loss .

         11. Subjects who are currently in the process of trying to quit cigarette smoking will be
             excluded.

         12. Female subjects of childbearing potential must agree to use medically accepted means
             of contraception. Pregnant and lactating female subjects will be excluded. People with
             a diagnosis of diabetes will only be included if their diabetes is currently treated
             and under control and have been on their current medication regimen for at 3 months.

         13. People with a blood pressure reading of 165/95 or greater at baseline will be excluded
             from the study.

         14. The concomitant use of medications that are known to alter weight or appetite,
             including anti-obesity drugs; corticosteroids; or nicotine substitutes will not be
             allowed (see Appendix 2: Medication Exclusion List). 15. Additionally, patients
             treated with a form of valproate will not be included in the study.

        16. Subjects must be judged competent to participate in the informed consent process (by
        passing the ESC with a score of 10/12) and provide voluntary informed consent.