Does a GLP-1 Receptor Agonist Change Glucose Tolerance in Antipsychotic-treated Patients? A Randomized, Double-blinded, Placebo-controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 103
- 试验地点
- 1
- 主要终点
- Glucose tolerance
研究概览
简要总结
Metabolic disturbances, obesity and life-shortening cardiovascular morbidity are major clinical problems among antipsychotic-treated patients. Especially two of the most efficacious antipsychotics, clozapine and olanzapine, cause weight gain and metabolic disturbances and can rarely be replaced by other drugs due to the effectiveness of the compounds. Glucagon-like peptide 1 (GLP-1) has improved glycemic control among patients with type 2 diabetes. The study will investigate whether the beneficial effects of GLP-1 analogues on glycemic control in type 2 diabetic patients, can be extended to a population of non-diabetic, dysglycemic psychiatric patients, receiving antipsychotic medical treatment.
详细描述
Statistical analyses:
Power calculation:
A sample size of 96 participants (48 in each group) was estimated, with two-sided t-testing, an α of 5% and a power of 90%. The power calculation was based on the primary outcome measurement: Change in glucose tolerance. The glucose tolerance was estimated by the total Area Under the Curve (AUC) following a 4-hour 75-g. Oral Glucose Tolerance Test (OGTT). The expected mean total AUC for the plasma glucose excursion following a 4-hour 75-g. OGTT was estimated as 1695 (SD 158) and 1800 (SD 158) after 16 weeks of treatment for the liraglutide and liraglutide placebo group, respectively. The difference in total AUC was based on unpublished data in individuals with and without Impaired Glucose Tolerance (IGT) following a 4-hour 75-g. OGTT at baseline from the study: "The Impact of Liraglutide on Glucose Tolerance and the Risk of Type 2 Diabetes in Women With Previous Pregnancy-induced Diabetes".(1)
Procedure:
All analyses will be carried out with the treatment groups still blinded and labeled as "treatment group A" and "treatment group B". Before dividing participants into group A and group B, the statistical plan was completed and uploaded on clinicaltrials.gov, and the data set was locked. The final unblinding of treatment groups (liraglutide or liraglutide placebo), will not be carried out until all statistical analyses are performed. All analyses will be performed using SAS 9.4, with α set at 0.05 and two-sided testing.
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
- •Informed oral and written consent
- •Diagnosed with schizophrenia, schizotypal disorder or paranoid psychosis according to the criteria of ICD10 (International Classification of Diseases, World Health Organization) or the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the American Psychiatric Association)
- •and on stable antipsychotic treatment with either clozapine or olanzapine for at least 6 months (without dose change for at least 30 days)
- •Stable co-medications for at least 30 days.
- •Age ≥18 years and ≤65 years
- •Stable weight (defined as less than 5% change in weight over the last 3 month before inclusion)
- •BMI ≥27 kg/m2
- •Dysglycaemia (IFG, i.e. fasting plasma glucose level from 6.1 mmol/L to 6.9 mmol/L or IGT, i.e. two-hour glucose levels > 7.8 mmol/L on the 75-g oral glucose tolerance test with a fasting plasma glucose of less than 7.0 mmol/L and HbA1c < 48 mmol/mol or HbA1c: 43 mmol/mol ≤ HbA1c ≤ 47 mmol/mol)
排除标准
- •Compulsory treatment
- •Females of child bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant or are not using adequate contraceptive measures
- •Subjects treated with corticosteroids or other hormone therapy (except estrogens)
- •Any active substance abuse or dependence for the past 6 months (except for nicotine)
- •Impaired hepatic function (liver transaminases >2 times upper normal limit)
- •Impaired renal function (se-creatinine >150 μM and/or macroalbuminuria)
- •Impaired pancreatic function (acute or chronic pancreatitis and/or amylase >2 times upper normal limit)
- •Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months
- •Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >100 mmHg)
- •Any condition that the investigator feels would interfere with trial participation
- •Receiving any investigational drug within the last 3 months
- •Use of weight-lowering pharmacotherapy within the preceding 3 month
- •Type 1 or 2 diabetes with HbA1c > 6.5%
- •Also a group of healthy controls (n=10) will have the baseline examinations done. The healthy controls will be matched to our participants in regards to gender, BMI and age. The same inclusion and exclusion criteria will apply for these controls, except these participants are not allowed to have known psychiatric illness, receive anti-psychotic medications, or have a family history of type 2 diabetes (2 generations).
研究组 & 干预措施
Liraglutide
Once a day 1,8 mg subcutaneous injection for 16 weeks
干预措施: Liraglutide (Drug)
Liraglutide placebo
Once a day 1,8 mg subcutaneous injection for 16 weeks
干预措施: Liraglutide Placebo (Drug)
结局指标
主要结局
Glucose tolerance
时间窗: Baseline - 16 weeks
Change in Glucose tolerance (measured by area under the curve (AUC) for plasma glucose (PG) excursion following a 4-hour 75 g Oral Glucose Tolerance Test (OGTT))
次要结局
- Secretion of incretin hormons, insulin sensitivity and beta cell function(Baseline - 16 weeks)
- Body composition(Baseline - 16 weeks)
- Body weight(Every 4 weeks from baseline - 16 weeks)
- Blood pressure(Every 4 weeks from baseline - 16 weeks)
- Lipid profile and liver function(Every 4 weeks from baseline - 16 weeks)
- Dysglycaemia(Baseline - 16 weeks)
- Psychopathology(Baseline - 16 weeks)
- Waist circumference(Every 4 weeks from baseline - 16 weeks)
研究者
Anders Fink-Jensen, MD, DMSci
Professor, MD, DMSci
Psychiatric Centre Rigshospitalet