The Effects of Rimonabant, on Weight and Metabolic Risk Factors

• Status: Terminated
• Trial end date: 2009-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Maryland; University of Maryland, Baltimore
• Collaborator: National Institute on Drug Abuse (NIDA)
• Treatments: Rimonabant

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.