The Effects of the Cannabinoid-1 Receptor Antagonist, Rimonabant, on Weight and Metabolic Risk Factors in People With Schizophrenia

University of Maryland, Baltimore4 个研究点分布在 1 个国家目标入组 17 人开始时间: 2007年11月最近更新: 2019年11月4日

适应症

干预措施

试验速览

阶段: 2 期
状态: 终止
发起方: University of Maryland, Baltimore
入组人数: 17
试验地点: 4
主要终点: Brief Psychiatric Rating Scale (BPRS) Total Score

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

Part I will be a 2-week evaluation phase. In Part I, subjects undergo a diagnostic interview for symptoms and treatment along with medical, side effect measures, and neuropsychological tests (tests for memory, attention, and motor task skills). An electrocardiogram (EKG), a urine sample, and about 3 tablespoons of blood will be taken for laboratory tests. Women will have a pregnancy test. This part of the study is 3-4 visits. The time of the visits will be about 8 hours.

Part II is a 16-week treatment phase subjects will be randomly assigned to either rimonabant or placebo for a 16-week period. The medication will be given in unmarked capsules so that subjects will not know which medication they are receiving. Only the pharmacist will know which medications subjects are receiving. If an emergency occurs we will break the blind and give appropriate care. This phase will require one visit every week and each visit may take up to 2-3 hours. Subjects will be examined every week to check symptoms side effects. Subjects symptoms will be evaluated using specially designed rating scales, to ask about their daily experiences and feelings. Evaluations that occur every 4 weeks may take about 2 hours. At week 8 and week 16 laboratory tests will be repeated. These tests will be compared to the baseline tests taken in Part I. The end of study tests may take up to a total of 8 hours and may require 3-4 visits. All testing is done for research purposes only and would not be performed if subjects were not participating in this study. The total number of visits requested for this study will be 16-20. When subjects undergo neuropsychological testing, we will examine their ability to learn and remember numbers and words to pay attention and to quickly perform motor tasks. A motor task is when you use your hands to perform a task such as placing pegs into a piece of wood. These tests will take about 2 hours and are done at the beginning of Part I and the end of Part II.

Diet and exercise counseling will be held weekly for groups and individuals. Sessions will focus on topics such as calories, fat content, portion control and determining a healthy weight. We will request that participants maintain a food diary and exercise approximately 30 minutes/3 times per week. Subjects will be encouraged to attend the counseling sessions. Transportation will be available for subjects. If patients have not attended sessions, they will be reeducated on the importance of attending sessions at the time of clinical ratings.Subjects will not be discharged from the study if they do not attend sessions.

Randomization will be done using a permuted block randomization system, and will be stratified by clozapine/olanzapine treatment at baseline. Treatment assignment order is random within each block, and the total number of patients assigned to each treatment is equal. The block sizes will vary between sizes 2 and 4 in random sequence. The unblinded pharmacist will be notified of the treatment assignment, and will inform unblinded pharmacists at the other sites about which study medication to dispense. In an emergency, research staff will be able to contact the pharmacy for unblinding. Rimonabant will be available in 20 mg capsules with matched placebo.

For outpatients study medication will be dispensed on a weekly basis plus two extra days of medication. Inpatient subjects will receive their study medication daily from the Maryland Psychiatric Research Center (MPRC) Treatment Research Program (TRP) central pharmacy by a non-blind pharmacist. The blind will be broken only if a medical emergency requires this information. If this occurs, the patient will be withdrawn from the study.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围: 18 Years 至 55 Years（Adult）
性别: All
接受健康志愿者: 否

入选标准

•Age range of 18-
•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).

排除标准

•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.
•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).
•Additionally, patients treated with a form of valproate will not be included in 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.

研究组 & 干预措施

1

Experimental

Rimonabant

干预措施: Rimonabant (Drug)

2

Placebo Comparator

Placebo

干预措施: Placebo (Drug)