A Randomized, Placebo-Controlled Study of Liraglutide 3mg Daily (Saxenda®) in Obese or Overweight Patients With Stable Bipolar Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Percent Change in Body Weight
研究概览
简要总结
Taken together these data support the hypothesis that liraglutide 3.0 mg sc injection will reduce body weight and improve metabolic variables in obese or overweight patients with BP without worsening psychiatric symptoms. The investigators predict that liraglutide 3.0 mg sc injection will display greater efficacy as compared to placebo in decreasing body weight in patients with BP who are obese or overweight. To prove this hypothesis, investigators will conduct a single-center, randomized, placebo-controlled, double-blind, parallel-group, 2-arm clinical trial of liraglutide 3.0 mg sc injection in 60 obese or overweight outpatients with stable BP. The investigators have chosen BP rather than another SMI because it is the most common SMI (more common than schizophrenia or schizoaffective disorder) and has a particularly strong association with obesity.
详细描述
BACKGROUND AND SIGNIFICANCE:
Obesity is common among persons with severe mental illness (SMI), especially those with bipolar disorder (BP) (1-5). It is estimated that 45-55% of people with SMI are obese, making obesity 1.5-2 times more common among those with SMI than among the general population. Indeed, in a recent pragmatic lithium trial conducted in BP, 69% of the subjects were overweight or obese. Although the precise mechanism underlying the relationship between obesity and SMI is unknown, it is thought to be multifactorial, involving genetic factors, intrinsic features of SMI (e.g., overeating, poor dietary choices, sedentary lifestyle, and sleep dysregulation), and the weight-gaining effects of most of the psychotropic medication used to treat SMI.
Importantly, obesity is thought to contribute to the well-documented elevated mortality from cardiovascular disease (CVD) among those with BP. Thus, weight reduction in obese people with BP might be important for reducing their morbidity and mortality from CVD and other obesity-related conditions (e.g., diabetes and metabolic syndrome). Conversely, the presence of obesity in patients with BP is associated with a more severe course of illness , a lower health-related quality of life (18), reductions in brain gray and white volumes (19, 20), and non-adherence with antipsychotic medications . Indeed, it has been hypothesized that successful treatment of obesity in those with BP might benefit mental as well as physical health. It is thus imperative that obesity be a focus of treatment in those with BP.
Comprehensive behavioral weight management programs have shown some effectiveness for obesity in patients with SMI, but the weight loss is modest at best and such programs are difficult to implement and not widely available. Several medications have been shown to mitigate psychotropic-induced weight gain, particularly metformin and topiramate, but many patients either do not respond to these agents or are unable to tolerate them. Importantly, the efficacy and safety of newly available weight-loss agents have not been evaluated in people with SMI.
In December 2014, the U.S. Food and Drug Administration approved liraglutide [rDNA origin] 3 mg/day subcutaneous [sc] injection) (Saxenda®) as a treatment option for chronic weight management in individuals with obesity. The drug is approved for use in adults with a body mass index (BMI) of 30 or greater (obesity) or adults with a BMI of 27 or greater (overweight) who have at least one weight-related comorbid condition such as hypertension, type 2 diabetes, or dyslipidemia, in combination with reduced-calorie diet and increased physical activity. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. Saxenda® and Victoza® contain the same active ingredient (liraglutide) at different doses (3 mg and 1.8 mg, respectively). However, unlike Victoza®, Saxenda® is not indicated for the treatment of type 2 diabetes, as the safety and efficacy of Saxenda® for the treatment of diabetes has not been established.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women, ages of 18-65 years, inclusive.
- •Participants will have a DSM-5 bipolar disorder that is clinically stable.
- •Participants will have received a stable major psychotropic drug regimen (except for minor dosage adjustments) for at least 3 months prior study entry. Major psychotropic drugs are antipsychotics, mood stabilizers, and antidepressants. Subjects may have had changes in adjunctive benzodiazepines and hypnotic agents.
- •Participants will be obese (defined as a BMI ≥ 30 mg/kg2) or overweight (defined as BMI ≥ 27 kg/m2) with at least one weight-related comorbidity, such as hypertension, type 2 diabetes, or dyslipidemia.
- •5 Participants in treatment for a weight-related comorbidity (hypertension, type 2 diabetes, and/or dyslipidemia) must be on a stable and allowed treatment regimen for that condition for at least 3 months prior to study enrollment.
- •6 Participants will be able to provide informed consent before any trial-related activities.
排除标准
- •Women who are pregnant, lactating, or of childbearing potential who are not using adequate contraceptive measures. The following are considered to be adequate methods of birth control: 1.Intrauterine device (IUD);
- •Barrier protection; 3.Contraceptive implantation system (Norplant); 4.Oral contraceptive pills;
- •A surgically sterile partner; and
- •Abstinence. Women who are > 2 years post-menopausal or surgically-sterile are not considered of childbearing potential. All female participants will have a negative pregnancy test prior to randomization.
- •Participants who have made a suicide attempt in the last 10 years, who are displaying clinically significant psychotic features, suicidality, or homicidality on mental status examination, or who have suicidal ideation or behavior as assessed with the C-SSRS.
- •Participants who are receiving behavioral weight loss treatment (BWLT) (e.g., Weight Watchers) that was begun within the 3 months before study entry. Participants who are receiving BWLT that was started 3 months prior to the beginning of the study will be allowed to continue to receive their BWLT during the trial only if they have had no weight loss in the past 3 months and they agree to not make any changes in the frequency or nature of their BWLT during the course of the drug trial.
- •A DSM-5 diagnosis of a substance-related or addictive disorder (except a tobacco-related disorder) within the 3 months prior to enrollment.
- •A DSM-5 diagnosis of dementia, a psychotic disorder, or a depressive disorder.
- •History of any psychiatric disorder which might interfere with a diagnostic assessment, treatment, or compliance.
- •Clinically unstable medical disease, including cardiovascular, hepatic, renal, gastrointestinal, pulmonary, neurological, metabolic, endocrine, or other systemic disease. Clinically stable hypertension, type 2 diabetes, or dyslipidemia are not exclusionary.
- •Have a history of a structural cardiac abnormality, valvular cardiac disease, cardiomyopathy, serious heart rhythm abnormality, coronary artery disease, congestive heart failure, stroke, or other serious cardiovascular problem.
- •Have an ECG with significant arrhythmias or conduction abnormalities, which in the opinion of the physician investigator preclude study participation.
- •Have clinically relevant abnormal laboratory results.
- •Participants requiring treatment with any drug which might interact adversely with or obscure the action of the study medication. This includes anti-obesity drugs, psychostimulants, modafinil or armodafinil, topiramate or zonisamide, and antipsychotics. Participants receiving metformin at a stable dose for ≥ 3 months can be included.
- •Participants receiving GLP-1 based therapies, sodium-glucose co-transporter 2 inhibitors (SGLT2s), thiazolidinediones, sulfonylureas, or insulin.
- •Participants with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type
- •Participants who have received any investigational medication within three months prior to randomization.
- •Participants previously screen-failed or randomised to participate in this trial.
- •Participants who have a known or suspected allergy to liraglutide 3.0 mg sc injection, its constituents, or related products.
- •Participants with a urine drug screen positive for a drug that, in the opinion of the investigator, is being abused.
- •Participants with a past medical history of pancreatitis.
- •Participants who had received any investigational drug within 3 months prior to this trial.
- •Participants who require bariatric surgery or are anticipated to require it during the course of the trial. If such surgery becomes warranted during the study, such patients will be excluded from the primary endpoint analysis.
研究组 & 干预措施
Active drug
LIRAGLUTIDE 3 Mg/0.5 mL (18 Mg/3 mL) SUB-Q PEN INJECTOR (ML)
干预措施: LIRAGLUTIDE (Drug)
Placebo
Placebo (no active drug)
干预措施: Placebo (Other)
结局指标
主要结局
Percent Change in Body Weight
时间窗: 40 week
Percent change in body weight over 40 weeks
次要结局
未报告次要终点
研究者
Susan McElroy
Chief Research Officer
Lindner Center of HOPE