Effectiveness of Pharmacologic, Surgical, and Dietetic Weight Loss Methods on Lifespan in Patients With Metabolic Syndrome: a Comparative Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Weight
研究概览
简要总结
Background. The prevalence of type 2 diabetes mellitus (T2D) in the world is constantly increasing. Treatment of T2D is complicated by arterial hypertension and obesity (metabolic syndrome - MS). Cardiovascular complications are the main cause of death in patients with MS. Objective weight loss improves clinical and laboratory parameters in patients with T2D and hypertension.
Purpose: To study lifespan, glycemic and lipid metabolism, quality of life, and cost-effectiveness of pharmacologic, surgical, and dietetic weight loss methods in obese patients with MS at 24 weeks in a comparative clinical trial.
Methods:
- st stage - Study design: An open pilot prospective clinical trial. The study included 71 adult patients with T2D and hypertension for the Ramadan fast's (RF) weight loss.
- nd stage - Study design: A 24-week open label, prospective, multicenter, comparative clinical trial with the intention-to-treat analysis.
Participants. Totally 150 adult patients with MS aged 35-65 years and with BMI≥27 kg/m2 for Asian will be included. They will be distributed in three comparative groups: drug treatment, surgery and diet.
Primary endpoints: weight loss, fasting blood glucose, blood insulin level, systolic/diastolic BP.
Secondary endpoints: blood lipids, heel bone mineral density (HBMD), and ejection fraction (EF).
Expected results:
A prospective multicenter clinical study will provide comparative results on life expectancy, glycemic and lipid metabolism, quality of life, cost-effectiveness of pharmacological, bariatric and dietary methods of weight loss in patients with obesity, T2D and hypertension. As a result of the research, the following will be published:
- at least three articles and/or reviews in peer-reviewed scientific publications indexed in the Science Citation Index Expanded of the Web Of Science database and/or having a Cite Score percentile in the Scopus of at least 50;
- at least 1 patent for an invention (including a positive decision on it).
详细描述
At the 1 st stage of the study will screen 71 adult patients for eligibility aged 35 to 65 years with T2D and hypertension for the RF. T2D was treated with Metformin, Sulfonylurea, GLP-1 agonists (exenatide, liraglutide), Glitazones in different combinations; hypertension was treated with beta-blockers, calcium channel blockers, diuretics, SGLT-2 Inhibitors (empagliflozin, canagliflozin) in different combinations. Patients with heart failure (HF) in their medical records and anamnesis with reduced ejection fraction <55% also will be included; I-II stages of the NYHA functional classification.
Inclusion criteria: 1) written informed consent; 2) 35≤ age <65 years old; 2) any BMI and WC; 3) diagnosis of T2D and hypertension ≥3 years and treatment with non-hormonal conventional pharmacological medications; 4) any level of triglycerides, cholesterol, body fat%; 5) weight loss on the RF for 30 days.
Exclusion criteria: 1) age <35 or ≥65 years old; 1) Insulin-depended T2D and uncontrolled high BP; 2) patients taking gastrointestinal lipase inhibitors, etc.; 3) presence of acute infection diseases or exacerbation of chronic diseases; 4) ejection fraction <30%; 5) history of alcohol consumption >30 g/day within the past 5 years; 6) malignancy within the past 5 years; gestation or lactation; kidney failure; hereditary diseases; or known hypersensitivity to any of the test substances.
Outcome measures: Primary endpoints: weight loss, fasting blood glucose, blood insulin level, systolic/diastolic BP. Secondary endpoints: blood lipids, heel bone mineral density (HBMD), and EF.
Intervention. The participants adhered to fasting on RF season. They strictly adhered to two principles of nutrition during RF: 1) "no blood, no smell of fat" which means "don't eat meat and don't eat fatty foods"; 2) the 'Sehri time' (a meal eaten before dawn) included just 1.5-2.0 glass of water and fruits of 80-100 gr (apple, dates, and persimmon). Indeed, the patients followed a diet in which they ate one meal a day - participants have a meal during 'Iftar time' (a meal eaten after sunset). The participants also adhered to walking at least 3,000 steps/day, sexual self-restraint.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •written informed consent;
- •T2D≥3-year with glucose lowering therapy including insulin;
- •35-55 years old;
- •BMI≥27 kg/m2 for both sex, for Asian ethnicity;
- •ongoing treatment with antihypertensive treatment;
- •weight loss 15-20% at baseline and dynamic follow-up up to 24 weeks.
排除标准
- •<34 age >56 years old;
- •unstable cardiac disorders (New York Heart Association class IV heart failure, refractory angina, uncontrolled arrhythmias, critical valvular heart disease, or severe uncontrolled hypertension);
- •glomerular filtration rate <30 mL/min and/or dialysis within 14 days before screening; • malignancy within the past 5 years;
- •gestation or lactation;
- •hereditary diseases;
- •known hypersensitivity to any of the test substances.
研究组 & 干预措施
Pharmacologic weight loss (Combination Product)
The 1st group (n=50) receives subcutaneous Semaglutide (GLP-1RA) 1 mg once a 7 day with oral Empagliflozin (SGLT-2i) 25 mg once a day that is a novel combination additionally to standard medical treatment including anti-diabetes, antihypertensive, lipid-lowering, symptomatic therapy.
干预措施: Semaglutide, Empagliflozin (Drug)
Surgical weight loss
The 2nd group (n=50) receives surgical method (laparoscopic MGB). These patients pass through additional pre-operation examination (blood tests and electrocardiography, esophagogastroscopy, ultrasound, and other necessary standard methods).
干预措施: Minigastric bypass (Procedure)
Very-low-calorie-restriction diet
The 3rd group (n=50) receives very-low-calorie-restriction diet ('Analimentary-detoxication') including <100 kcal/day with fat-free vegetables (tomato/cucumber) and salt intake (5-6 g/day), optimum physical activity, and sexual self-restraint. The program goals the next outputs: a) use of own fatty store; b) control endogen intoxication; c) reuse of interim metabolic substrates.
干预措施: Analimentary detoxication (Dietary Supplement)
Ramadan fast's weight loss
The 4th group (n=30) adheres to fasting on Ramadan fast (RF) season. They strictly adhered to two principles of nutrition during RF: 1) "no blood, no smell of fat" which means "don't eat meat and don't eat fatty foods"; 2) the 'Sehri time' (a meal eaten before dawn) included just 1.5-2.0 glass of water and fruits of 80-100 gr (apple, dates, and persimmon). Indeed, the patients followed a diet in which they ate one meal a day - participants have a meal during 'Iftar time' (a meal eaten after sunset).
干预措施: Ramadan fast's weight loss (Behavioral)
结局指标
主要结局
Weight
时间窗: Baseline, 24 weeks
weight in kilograms
blood insulin level
时间窗: Baseline, 24 weeks
Fasting serum insulin (nU/L) was determined by immunoassay (Immunotech Insulin Irma kit, Prague, Czech Republic)
Fasting blood glucose
时间窗: Baseline, 24 weeks
mmol per liter
Body mass index
时间窗: Baseline, 24 weeks
weight and height will be combined to report BMI in kg/m\^2
Fat mass
时间窗: Baseline, 24 weeks
fat mass in % of total body weight and total kg
systolic/diastolic Blood presure
时间窗: Baseline, 24 weeks
Blood pressure is measured in units of millimeters of mercury (mmHg). The readings are always given in pairs, with the upper (systolic) value first, followed by the lower (diastolic) value.
Fat free mass
时间窗: Baseline, 24 weeks
fat free mass in % of total body weight and total kg
次要结局
- Total cholesterol(Baseline, 24 weeks)
- HbA1c(Baseline, 24 weeks)
- Triglycerides(Baseline, 24 weeks)
- High-density lipoprotein(Baseline, 24 weeks)
研究者
Kuat Oshakbayev
full-Professor
University Medical Center, Kazakhstan