Diastolic Dysfunction Clinical Trial
— FITOfficial title:
Effects of Ciprofibrate on Myocardial Insulin Sensitivity in Pre-diabetes
Verified date | January 2021 |
Source | Maastricht University Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Free fatty acids (FFA) are the main fuel source in a healthy adult heart, since they are responsible for 70-80% of the myocardial ATP production. Plasma FFA and triglycerides (TG) levels are elevated in obesity and diabetes, evoking substrate competition in the heart: the increased availability of lipids will lead to fat accumulation in the heart, which is associated with cardiac insulin resistance and will therefore restrain insulin-stimulated cardiac glucose oxidation. It is shown that a lower myocardial glucose uptake correlates with decreased diastolic function. The benefits of counterbalancing this lipid overload is proven by previous research in pre-diabetes, which showed the reversibility of impaired myocardial substrate metabolism and improvement of function and structure after modest weight loss induced by lifestyle changes. Ciprofibrates are a ligand of the peroxisome proliferator-activated receptor (PPAR) α and are considered to be a major regulator of the lipid metabolism and promote fat oxidative capacity. They are not only effective in normalizing lipid-lipoprotein levels in patients with the metabolic syndrome, but improve also their insulin sensitivity. We therefore hypothesize that ciprofibrate administration in subjects with impaired glucose metabolism (IGM) influence the myocardial substrate metabolism (via the PPARα pathway) and thereby improve myocardial insulin sensivity.
Status | Completed |
Enrollment | 11 |
Est. completion date | November 13, 2020 |
Est. primary completion date | November 6, 2020 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 40 Years to 70 Years |
Eligibility | Inclusion Criteria: - Race: caucasian - Sex: male - Age: 40-70 years - BMI: 27-35 kg/m2 - Stable dietary habits: no weight gain or loss > 5kg in the last three months - Insulin resistant: glucose clearance rate below < 360 ml/kg/min, as determined using OGIS120 Exclusion Criteria: - Patients with a cardiac disease or with instable angina - Patients with hepatic or renal failure - Haemoglobin <7.8 mmol/l - In case of an abnormal ECG in rest: this will be discussed with the responsible medical doctor - HbA1c > 6.5% - Diagnosed with type 1 or type 2 diabetes mellitus - Patients with alcohol abuse - Use of a fibrate - Medication use known to interfere with glucose homeostasis/metabolism - Use of anti-coagulants, excluding platelet aggregation inhibitors - Subjects who do not want to be informed about unexpected medical findings during the screening /study, or do not wish that their physician is informed, cannot participate in the study. - Subjects who intend to donate blood during the intervention or subjects who have donated blood less than three months before the start of the intervention. - Participation in another biomedical study within 1 month before the first screening visit - Any condition, disease or abnormal laboratory test result that, in the opinion of the Investigator, would interfere with the study outcome, affect trial participation or put the subject at undue risk - Any contra-indication to MRI scanning. These contra-indications include patients with following devices: - Electronic implants such as pacemakers or defibrillator or neurostimulator - Central nervous system aneurysm clip - Some hearing aids (such as cochlear implant) and artificial (heart) valves which are contraindicated for MRS - Iron containing corpora aliena in the eye or brains - Claustrophobia - Participation in earlier research or medical examinations in the past 3 months that included PET/MRI scanning |
Country | Name | City | State |
---|---|---|---|
Netherlands | Nutrition and Movement Sciences | Maastricht | Limburg |
Lead Sponsor | Collaborator |
---|---|
Maastricht University Medical Center | Maastricht University |
Netherlands,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Myocardial insulin sensitivity | measured by the insulin-stimulated myocardial glucose uptake by FDG-PET | 1hour, day 35 | |
Secondary | Hepatic glucose uptake | measured by the insulin-stimulated myocardial glucose uptake by FDG-PET | 1hour, day 35 | |
Secondary | Skeletal muscle glucose uptake | measured by the insulin-stimulated myocardial glucose uptake by FDG-PET | 1hour, day 35 | |
Secondary | Brown adipose tissue (BAT) glucose uptake | measured by the insulin-stimulated myocardial glucose uptake by FDG-PET | 1hour, day 35 | |
Secondary | Insulin sensitivity | Glucose infusion rate (GIR) from the hyperinsulinemic euglycemic clamp | 4hours, day 35 | |
Secondary | Intracardiomyocellular lipid content | Cardiac 1H-MRS: fasted & insulin-stimulated | 1hour, day 35 | |
Secondary | Cardiac systolic function | Functional cardiac MRI: fasted & insulin-stimulated | 1hour, day 35 | |
Secondary | In vivo myocardial mitochondrial function (PCr/ATP ratio) | Cardiac 31P-MRS: fasted | 1hour, day 28 | |
Secondary | Cardiac diastolic function | Cardiac ultrasound | 1hour, day 34 | |
Secondary | Intrahepatic lipid content and hepatic lipid composition | Hepatic 1H-MRS: fasted | 1hour, day 28 | |
Secondary | Blood pressure | 24-hour blood pressure monitor | 24hours, day 27 | |
Secondary | Whole body (sleeping) energy metabolism (sleeping energy expenditure and substrate oxidation) | Respiration chamber: overnight | 12 hours, day 34 | |
Secondary | Whole body maximum aerobic capacity | VO2 max test | 1hour, day 28 | |
Secondary | Total body mass and fat mass | Body composition | 0.5 hour, day 35 | |
Secondary | Ex vivo PPARalpha expression and downstream targets | Skeletal muscle biopsy | 0.5 hour, day 35 | |
Secondary | Postprandial lipid response | Meal test | 5hour, day 34 | |
Secondary | Anti-inflammatory effects (in the long term on the immune cells; acute effect on postprandial response), circadian rhythm | PBMC | 6hour, day 0-34-35 | |
Secondary | Cholesterol profile | Blood after venapunction | 5hours, day 0,7,14,21,28,35 |
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