The Effects of Rimonabant, on Weight and Metabolic Risk Factors

NCT00547118 | Terminated Phase 2 Results DMC

• 1 other identifier: HP-00041206
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 4

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Obesity; Hypertension; Smoking

Keywords

Metabolic abnormalities; Safety; Satiety

Outcome Measures

Primary Outcomes (7)

• Brief Psychiatric Rating Scale (BPRS) Total Score

  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.

  Baseline (Week 0) and end of study (Week 16)

• Brief Psychiatric Rating Scale (BPRS) Psychosis Score

  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.

  Baseline (Week 0) and end of study (Week 16)

• The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

  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.

  Baseline (Week 0) and end of study (Week 16)

• The Iowa Gambling Task (IGT)

  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.

  Baseline (Week 0) and end of study (Week 16)

• N-Back Neurocognitive Task: 0-back Condition

  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.

  Baseline (Week 0) and end of study (Week 16)

• N-Back Neurocognitive Task: 1-back Condition

  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.

  Baseline (Week 0) and end of study (Week 16)

• N-Back Neurocognitive Task: 2-back Condition

  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.

  Baseline (Week 0) and end of study (Week 16)

Secondary Outcomes (7)

• Schedule for Assessment of Negative Symptoms (SANS) Total Score

  Baseline (Week 0) and end of study (Week 16)

• Schedule for Assessment of Negative Symptoms (SANS) - Anhedonia

  Baseline (Week 0) and end of study (Week 16)

• Schedule for Assessment of Negative Symptoms (SANS) - Blunted Affect

  Baseline (Week 0) and end of study (Week 16)

• Schedule for Assessment of Negative Symptoms (SANS) - Alogia

  Baseline (Week 0) and end of study (Week 16)

• Schedule for Assessment of Negative Symptoms (SANS) - Avolition

  Baseline (Week 0) and end of study (Week 16)

Study Arms (2)

1

EXPERIMENTAL

Rimonabant

Drug: Rimonabant

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Rimonabant DRUG

One 20 mg tablet given 1 time per day for 112 days.

1

Placebo DRUG

One placebo tablet given 1 time per day for 112 days.

2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Any gender
• Any race,
• Age range of 18-55.
• Meet DSM-IV (APA, 1994) criteria for either schizophrenia or schizoaffective disorder.
• 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
• Be treated with the same SGA for at least 8 weeks and to have received a constant therapeutic dose for at least 30 days
• 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).

You may not qualify if:

• 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).
• 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.
• Subjects with nicotine use or dependence will not be excluded.
• 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)
• Subjects with a history of Crohn's Disease or Irritable Bowel Syndrome
• Subjects with a organic brain disorder
• A DSM-IV eating disorder
• 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).
• 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.
• Subjects with a history of surgical procedures for weight loss .
• Subjects who are currently in the process of trying to quit cigarette smoking will be excluded.
• 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.
• People with a blood pressure reading of 165/95 or greater at baseline will be excluded from the study.
• \. 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.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (4)

Baltimore VA Medical Center

Baltimore, Maryland, 21201, United States

Location

Keypoint Health System

Baltimore, Maryland, 21201, United States

Location

Sheppard Pratt Health System

Baltimore, Maryland, 21201, United States

Location

Maryland Psychiatric Research Center (MPRC) Outpatient Research Program (ORP); the MPRC Treatment Research Program (TRP)

Catonsville, Maryland, 21228, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Obesity; Hypertension; Smoking

Interventions

Rimonabant

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Behavior

Intervention Hierarchy (Ancestors)

Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines

Results Point of Contact

• Title: Dr. Robert W. Buchanan
• Organization: Maryland Psychiatric Research Center

rwbuchanan@mprc.umaryland.edu

410-402-7876

Study Officials

• Robert W Buchanan, MD

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Robert Buchanan, MD

Study Record Dates

• First Submitted: October 19, 2007
• First Posted: October 22, 2007
• Study Start: November 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: November 4, 2019
• Results First Posted: February 27, 2015

Record last verified: 2019-10

Locations

US (4)