MaasFlex: Double-Blind, Randomized, Phase IV, Mechanistic, Placebo-Controlled, Cross-Over, Single-Center Study to Evaluate the Effects of 2 Weeks Dapagliflozin Treatment on Nocturnal Substrate Oxidation, Glucose Metabolism and Muscle Mitochondrial Function in Individuals With Impaired Glucose Homeostasis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Change in nightly substrate oxidation measured as respiration quotient (RQ) during the sleeping period
研究概览
简要总结
The purpose of this study is to investigate the effect of 2 weeks dapagliflozin treatment in individuals with a disrupted glucose homeostasis on the switch between carbohydrate and lipid oxidation during the night
详细描述
To investigate if dapagliflozin improves nocturnal substrate oxidation expressed as respiration quotient (RQ) during the sleeping period in comparison with placebo after 2-weeks double blind treatment in subjects with a disrupted glucose homeostasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provision of signed and dated informed consent prior to any study specific procedures.
- •Males aged ≥ 40 and ≤ 75 years and post-menopausal women (defined as at least 1 year post cessation of menses) aged ≥ 50 and ≤ 75 years
- •Body mass index (BMI) ≥ 27 and ≤ 38 kg/m
- •Sedentary lifestyle (not more than 3 hours of programmed exercise per week).
- •Stable dietary habits.
- •Impaired glucose homeostasis based on one or a combination of the following criteria:
- •Impaired Glucose Tolerance (IGT): plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1 mmol/l 120 minutes after consumption of the glucose drink during the 2h, 3-point OGTT.
- •Impaired Fasting Glucose (IFG): fasting plasma glucose ≥ 6.1 mmol/l and ≤ 6.9 mmol/l.
- •Insulin Resistance: glucose clearance rate ≤ 360 ml/kg/min, as calculated by Oral Glucose Insulin Sensitivity 120 (OGIS120) model based on the 2h, 3-point OGTT.
- •HbA1c ≥ 5.7% and ≤ 6.4%.
排除标准
- •Clinical diagnosis of Type 1 or 2 Diabetes Mellitus.
- •Active cardiovascular disease: participants who experienced a heart attack in the last year, or participants who are currently under regular control of a physician for a heart condition.
- •Weight gain or loss > 5 kg in the last 3 months, ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.
- •Regular smoking and other regular nicotine use.
- •Uncontrolled hypertension.
- •Clinically significant out of range values of serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) in the Investigator's opinion.
- •Unstable or rapidly progressing renal disease or estimated Glomerular Filtration Rate (eGFR) <60 mL/min (Cockcroft-Gault formula).
- •Use of anti-coagulant treatment and other concomitant medication will be evaluated on a case to case basis with a general physician.
- •Use of medication such as oral glucocorticoids, anti-estrogens or other medications that are known to markedly influence insulin sensitivity.
- •Use of loop diuretics.
- •Intake of dietary supplements except multi-vitamins and minerals.
- •Alcohol consumption of > 14 drinks per week for women and > 21 drinks per week for men (1 drink = 35 cl beer, 14 cl wine or 4 cl hard liquor).
- •Known hypersensitivity to dapagliflozin or any of the excipients of the product.
- •For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
- •Participation in another biomedical study within 1 month before the screening visit.
- •Any contraindication for MRI scanning.
- •Participants who do not want to be informed about unexpected medical findings, or do not wish that their physician be informed about coincidental findings, cannot participate in the study.
研究组 & 干预措施
Dapagliflozin 10 mg
Patients will receive dapagliflozin 10 mg in tablet for a maximum of 14 days based on randomization sequence in Period 1.
Patients that received 10 mg dapagliflozin in the first treatment period will receive matching placebo in the second treatment period for a maximum of 14 days.
干预措施: Dapagliflozin 10mg (Drug)
Placebo matching to dapagliflozin 10 mg
Patients will receive matching placebo in tablet for a maximum of 14 days based on randomization sequence.
Patients who received placebo in the first treatment will receive 10 mg dapagliflozin in the second treatment period, for a maximum of 14 days
干预措施: Placebo matching to Dapagliflozin 10 mg (Drug)
结局指标
主要结局
Change in nightly substrate oxidation measured as respiration quotient (RQ) during the sleeping period
时间窗: From screening to day 14
Comparison of dapagliflozin versus placebo after 14 days of treatment on nightly substrate oxidation as measured by respiratory quotient (VCO2/VO2) during the sleeping period.
次要结局
- Change in morning and late afternoon hepatic glycogen content(1 hour)
- Change in 24h substrate oxidation as determined by indirect calorimetry in a whole-body respiratory chamber and based on urinary nitrogen excretion(24 hours)
- Change in 24h plasma markers(24 hours)
- Change in muscle mitochondrial function(60 minutes)
- Change in intrahepatic lipid content and composition(45 minutes)
- Change in intramyocellular lipid content and composition - including acylcarnitine levels(45 minutes)
- Change in muscle glycogen content(45 minutes)
- Change in systolic and diastolic blood pressure(45 minutes)
研究者
Patrick Schrauwen
Prof. Dr.
Maastricht University