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The Effects of Rimonabant, on Weight and Metabolic Risk Factors

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ClinicalTrials.gov Identifier: NCT00547118
Recruitment Status : Terminated (Withdrawn due to medication withdrawal from the EMEA)
First Posted : October 22, 2007
Results First Posted : February 27, 2015
Last Update Posted : January 17, 2018
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
MPRC, University of Maryland

Brief 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.


Condition or disease Intervention/treatment Phase
Schizophrenia Schizoaffective Disorder Obesity Hypertension Smoking Drug: Rimonabant Drug: Placebo Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of the Cannabinoid-1 Receptor Antagonist, Rimonabant, on Weight and Metabolic Risk Factors in People With Schizophrenia
Study Start Date : November 2007
Actual Primary Completion Date : March 2009
Actual Study Completion Date : March 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1
Rimonabant
Drug: Rimonabant
One 20 mg tablet given 1 time per day for 112 days.
Placebo Comparator: 2
Placebo
Drug: Placebo
One placebo tablet given 1 time per day for 112 days.



Primary Outcome Measures :
  1. Brief Psychiatric Rating Scale (BPRS) Total Score [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    The total BPRS score is calculated by adding the scores for scales #1-#18. Each scale ranges from "1=Not Present" to "7=Very Severe". Total scores range from a minimum score of 18 to a maximum score of 126. A higher total score indicates a more severe psychiatric symptom rating.

  2. Brief Psychiatric Rating Scale (BPRS) Psychosis Score [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    The psychosis score is calculated by adding the scores for scales #4 Conceptual Disorganization, #11 Suspiciousness, #12 Hallucinatory Behavior, and #15 Unusual Thought Content. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum psychosis score is 4 and the maximum psychosis score is 28. A higher score indicates a more severe psychosis rating.

  3. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    The RBANS is a brief, individually administered test designed to evaluate neuropsychological status of adults, ages 20-89. The 12 subtests measure attention, language, visuospatial/constructional abilities, and immediate and delayed memory. The raw scores from the subtests are scaled together to create index scores, and these are summed for conversion to a total scale score. Higher score equals a better outcome. The total index score range for the RBANS is 40-160.

  4. The Iowa Gambling Task (IGT) [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    The Iowa Gambling Task (IGT) is a computer-administered cognitive test that assesses risk preferences by simulating real-life decision making using uncertainty, rewards, and penalties. In the task, players are given four decks of cards and an endowment of fake money (e.g., $2000). Players are instructed to select cards one at a time and try to lose the least amount of money and win the most. The outcome measure was the number of rewarded minus punished card choices. Task has a maximum of 100 trials. The net score is the difference between the number of choices from advantageous decks verses disadvantageous decks. Higher scores are better and can range from -50 to +50.

  5. N-Back Neurocognitive Task: 0-back Condition [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    The N-Back task is a sequential letter working memory task. D-prime was used to measure accuracy on the 0-back, 1-back, and 2-back conditions. D-prime scores range from 0 to 8.6. Higher scores are better. As memory load increases from 0 to 1, from 1 to 2, D-prime scores are expected to be lower.

  6. N-Back Neurocognitive Task: 1-back Condition [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    The N-Back task is a sequential letter working memory task. D-prime was used to measure accuracy on the 0-back, 1-back, and 2-back conditions. D-prime scores range from 0 to 8.6. Higher scores are better. As memory load increases from 0 to 1, from 1 to 2, D-prime scores are expected to be lower.

  7. N-Back Neurocognitive Task: 2-back Condition [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    The N-Back task is a sequential letter working memory task. D-prime was used to measure accuracy on the 0-back, 1-back, and 2-back conditions. D-prime scores range from 0 to 8.6. Higher scores are better. As memory load increases from 0 to 1, from 1 to 2, D-prime scores are expected to be lower.


Secondary Outcome Measures :
  1. Schedule for Assessment of Negative Symptoms (SANS) Total Score [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    SANS total score range = 0-85. Higher scores indicate more severe negative symptoms.

  2. Schedule for Assessment of Negative Symptoms (SANS) - Anhedonia [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    SANS Global Anhedonia score. Scores can range from 0-5, with higher scores indicating more severe anhedonia.

  3. Schedule for Assessment of Negative Symptoms (SANS) - Blunted Affect [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    SANS Global Rating of Affective Flattening. Scores can range from 0-5, with higher scores indicating more severe blunted affect.

  4. Schedule for Assessment of Negative Symptoms (SANS) - Alogia [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    SANS Global Rating of Alogia. Scores can range from 0-5, with higher scores indicating more severe alogia.

  5. Schedule for Assessment of Negative Symptoms (SANS) - Avolition [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    SANS Avolition score. Scores can range from 0-5, with higher scores indicating more severe avolition.

  6. Clinical Global Impression (CGI) [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    The global improvement score can range from 1-7, with higher scores indicating worse total improvement clinically.

  7. Calgary Depression Scale (CDS) Total Score [ Time Frame: Baseline (Week 0) and end of study (Week 16) ]
    The CDS total score is the addition of scores from items 1-9. Each item's scores range on a scale of "0=Absent" to "3=Severe". The total score range is from 0-27. Higher total scores indicate a more severe depression rating.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00547118


Locations
United States, Maryland
Baltimore VA Medical Center
Baltimore, Maryland, United States, 21201
Keypoint Health System
Baltimore, Maryland, United States, 21201
Sheppard Pratt Health System
Baltimore, Maryland, United States, 21201
Maryland Psychiatric Research Center (MPRC) Outpatient Research Program (ORP); the MPRC Treatment Research Program (TRP)
Catonsville, Maryland, United States, 21228
Sponsors and Collaborators
University of Maryland
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Robert W Buchanan, MD University of Maryland

Responsible Party: MPRC, Robert Buchanan, MD, University of Maryland
ClinicalTrials.gov Identifier: NCT00547118     History of Changes
Other Study ID Numbers: HP-00041206
First Posted: October 22, 2007    Key Record Dates
Results First Posted: February 27, 2015
Last Update Posted: January 17, 2018
Last Verified: January 2018

Keywords provided by MPRC, University of Maryland:
Metabolic abnormalities
Safety
Satiety

Additional relevant MeSH terms:
Schizophrenia
Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Rimonabant
Cannabinoid Receptor Antagonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs