Diabetes Interventional Assessment of Slimming or Training to Lessen Inconspicuous Cardiovascular Dysfunction. The Diastolic Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Increase in circumferential PEDSR rate as measured by CMR at 12 weeks.
研究概览
简要总结
There is an epidemic of type 2 diabetes in younger adults. These patients are at very high lifetime risk of heart-related complications. Subtle heart abnormalities can be present even at a young age in these patients and may predispose them to heart failure and ultimately premature death. There is emerging evidence that type 2 diabetes can be reversed with weight loss. We propose that weight loss can also reverse the fatty changes seen in the liver and heart in these patients, and in turn lead to improved heart function.
This project aims to identify how type 2 diabetes causes changes in the heart in young people with type 2 diabetes by performing detailed scans and other tests of the heart's structure and function. In addition we will attempt to see if the heart's pumping function can be improved, either by a weight loss program with a special low calorie diet, or by a structured program of exercise. This will be compared with the usual standard diabetes care.
As well as looking to see if the heart's function can be improved with the intervention, we also aim to identify what the mechanism of any improvement would be. We suspect that changes in the amount of fat within the liver and the heart may be responsible, and will measure these at the beginning, end and in some patients halfway through the study to explore possible mechanisms amongst other clinical variables (e.g. HbA1c)
详细描述
This is a single centre study, which will comprise of a cross-sectional analysis of the baseline data of a 3-arm 12 week Prospective, Randomised, Open label, Blinded End point (PROBE) trial of TDR and an exercise programme compared with standard care. Clinical follow-up will take place at 6-12 months.
The trial has two primary objectives:
- Identify the determinants of diastolic dysfunction, assessed by MRI, in younger adults with T2DM through multivariate analysis of baseline dataset (cross-sectional study analysis) 2) Determine if diastolic dysfunction (classified by diastolic strain rate) can be reversed by either TDR or an exercise programme (PROBE trial)
Secondary objectives include:
- Determine the reference range for diastolic strain rate in healthy adults
- Determine the optimum field strength for the assessment of PEDSR
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
- Single (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
- 是
入选标准
- •Capacity to provide informed consent before any trial-related activities
- •Established T2DM (≥3months)
- •HbA1c ≤ 9% if on triple therapy or ≤ 10% on diet & exercise or monotherapy or dual therapy
- •Current glucose lowering therapy either mono, dual or triple of any combination of metformin, sulphonylurea, DPP-IV inhibitor, GLP-1 therapy or an SGLT2 +/- diet and exercise
- •Poorly managed diet controlled diabetes (with HbA1c > 6.5% , not currently taking any glucose lowering therapy, meeting BMI inclusion range)
- •Body mass index > 30Kg/m2 or > 27.5 Kg/m2 (South Asian),
- •Diagnosis of T2DM before the age of 60 years of age
- •Age ≥18 and ≤ 65 years
排除标准
- •• Diabetes duration >12 years
- •Currently taking more than three glucose lowering therapies
- •Weight-loss of >5kg in the preceding 6 months
- •Stage 4 or 5 chronic kidney disease (eGFR< 30ml/min/1.73m2),
- •Current therapy with Insulin, thiazolidinediones, steroids or atypical antipsychotic medication
- •Untreated thyroid disease
- •Known macrovascular disease including coronary artery disease, stroke/TIA or peripheral vascular disease
- •Presence of arrhythmia (including atrial fibrillation, atrial flutter, or 2nd or 3rd degree atrioventricular block)
- •Known heart failure
- •Other clinically relevant heart disease
- •Inability to exercise or undertake a MRP
- •Absolute contraindication to CMR
- •Cardiovascular symptoms (angina, limiting dyspnoea during normal physical activity)
- •Inflammatory condition e.g. Connective tissue disorder, Rheumatoid arthritis
结局指标
主要结局
Increase in circumferential PEDSR rate as measured by CMR at 12 weeks.
时间窗: 12 weeks
The aim of these analyses is to compare the primary outcome (diastolic strain rate) measured by CMR at 12 weeks between the TDR and standard care arms, and between the exercise and standard care arms. The primary analysis will be a per protocol analysis as this is a proof of principle study where we are primarily interested in the size of the treatment effect, rather than the practicability of the intervention.
次要结局
- Adiponectin(Baseline, 4weeks, 12 weeks)
- Hypoglycaemia(Baseline, 4weeks, 12 weeks)
- Left ventricular mass(Baseline, 4 and 12 weeks)
- End diastolic volume(Baseline, 4 and 12 weeks)
- End systolic volume(Baseline, 4 and 12 weeks)
- Food Diary(Baseline, 12 weeks)
- Abdominal Subcutaneous (Superficial) distribution(0 (consultation), 4 and 12 weeks)
- Myocardial Systolic strain (Circumferential & Longitudinal)(Baseline, 4 and 12 weeks)
- Systolic Strain Rates(Baseline, 4 and 12 weeks)
- Abdominal Subcutaneous (Deep) distribution(0 (consultation), 4 and 12 weeks)
- Physical Fitness & activity (Peak VO2max)(Baseline, 4 weeks and 12 weeks)
- Insulin(Baseline, 4weeks, 12 weeks)
- Thyroid Function Tests (TFT)(Baseline, 4weeks, 12 weeks)
- Vitamin C(Baseline, 4weeks, 12 weeks)
- Group B Vitamin Panel(Baseline, 4weeks, 12 weeks)
- Myocardial triglyceride content(Baseline, 4 and 12 weeks)
- Triglycerides(Baseline, 4weeks, 12 weeks)
- Liver Function Test (LFT)(Baseline, 4weeks, 12 weeks)
- Iron(Baseline, 4weeks, 12 weeks)
- Waist & Hip Circumference(Baseline, 12 weeks)
- Heart rate(Baseline, 1, 2, 4, 6, 8, 12 weeks, 26 weeks, 52 weeks)
- 7-Point Profile Glucose Monitoring(0weeks, 4weeks, 12 weeks)
- Adverse Events(Baseline, 1, 2, 4, 6, 8, 12 weeks)
- Exercise Questionnaire(Baseline, 12 weeks)
- EQ5D Questionnaire(Baseline, 12 weeks)
- Ejection Fraction(Baseline, 4 and 12 weeks)
- Pulse-wave velocity(Baseline, 4 and 12 weeks)
- Liver triglyceride content(Baseline, 4 and 12 weeks)
- Myocardial Relaxation(Baseline, 4 and 12 weeks)
- Family & Full Medical History(Baseline)
- Leptin(Baseline, 4weeks, 12 weeks)
- LDL (Low density lipoprotein)(Baseline, 4weeks, 12 weeks)
- HDL (High density lipoprotein)(Baseline, 4weeks, 12 weeks)
- B-Type Natriuretic Peptide (BNP)(Baseline, 4weeks, 12 weeks)
- Metabolomic and Inflammatory Markers(Baseline, 4weeks, 12 weeks)
- Vitamin D(Baseline, 4weeks, 12 weeks)
- C-peptide(Baseline, 4weeks, 12 weeks)
- Weight(Baseline, 1, 2, 4, 6, 8, 12 weeks, 26 weeks, 52 weeks)
- LA Volumes(Baseline, 4 and 12 weeks)
- Non-Invasive Marker of Left Ventricular Filling Pressure(Baseline, 4 and 12 weeks)
- Adiposity (Fat Free Mass)(0 (consultation), 4 and 12 weeks)
- Physical Fitness & activity (Accelerometer)(Baseline, 4 weeks and 12 weeks)
- Total Cholesterol(Baseline, 4weeks, 12 weeks)
- Serum Ferritin(Baseline, 4weeks, 12 weeks)
- Full Blood Count (with Haematocrit)(Baseline, 4weeks, 12 weeks)
- Height(Baseline)
- Systolic and Diastolic BP(Baseline, 1, 2, 4, 6, 8, 12 weeks, 26 weeks, 52 weeks)
- Mean Ascending & Descending Aortic Distensibility(Baseline, 4 and 12 weeks)
- Global Myocardial Perfusion Reserve(Baseline, 4 and 12 weeks)
- Extracellular volume (ECV)(Baseline, 4 and 12 weeks)
- Mitral Inflow Velocity(Baseline, 4 and 12 weeks)
- Adiposity (Total Body Fat)(0 (consultation), 4 and 12 weeks)
- HbA1c(Baseline, 4weeks, 12 weeks)
- Fasting Glucose(Baseline, 1 week, 2 week, 4weeks, 12 weeks)