Ciprofibrate and Pre-diabetes (FIT)
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|ClinicalTrials.gov Identifier: NCT03662984|
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : February 21, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Myocardial Insulin Sensitivity Impaired Glucose Metabolism Diastolic Dysfunction||Drug: Ciprofibrate 100Mg Tablet Drug: Placebo Oral Tablet||Phase 3|
Objectives: The main objective of the study is to investigate whether ciprofibrate treatment can improve myocardial insulin sensitivity in subjects with IGM. As secondary objectives we want to investigate whether ciprofibrate treatment also improves diastolic and myocardial mitochondrial function and decreases intracardiomyocellular lipid content. Futhermore, since ciprofibrate could also affect cardiac metabolism indirectly, we want to investigate the effect of ciprofibrate on skeletal and hepatic glucose uptake, hepatic lipid storage and composition.
Study design: In a randomized, double-blind, cross-over design, the effects of ciprofibrate supplementation on myocardial insulin sensitivity will be compared to placebo in humans with IGM.
Study population: Twelve male, overweight (BMI > 27 kg/m2), insulin-resistant subjects, aged between 40 and 70 years, without cardiac disease, will participate in this study.
Intervention: Subjects will be asked to take one pill of ciprofibrate 100mg, or placebo, once daily (at dinner), for 35 days.
Main study parameters/endpoints: The main study endpoint is the difference in myocardial insulin sensitivity (measurement of glucose uptake using radio-active labeled 18F-FDG tracer in PET-MRI) after ciprofibrate administration compared to the placebo trial.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||Effects of Ciprofibrate on Myocardial Insulin Sensitivity in Pre-diabetes|
|Actual Study Start Date :||November 1, 2018|
|Estimated Primary Completion Date :||August 30, 2020|
|Estimated Study Completion Date :||August 30, 2020|
Active Comparator: Ciprofibrate
1dd100mg at breakfast
Drug: Ciprofibrate 100Mg Tablet
Ciprofibrate is a PPARα ligand and is considered to be a major regulator of the lipid metabolism. PPARα regulates the genes involved in mitochondrial function and fat metabolism and is therefore abundantly expressed in tissues that require high rates of FFA oxidation, like for instance in the heart and activation of PPARα in the heart may have beneficial effects on mitochondrial function and fat oxidative capacity.
Other Name: PPARa agonist
Placebo Comparator: Placebo
1dd0mg at breakfast
Drug: Placebo Oral Tablet
To compare ciprofibrate
- Myocardial insulin sensitivity [ Time Frame: 1hour, day 35 ]measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
- Hepatic glucose uptake [ Time Frame: 1hour, day 35 ]measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
- Skeletal muscle glucose uptake [ Time Frame: 1hour, day 35 ]measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
- Brown adipose tissue (BAT) glucose uptake [ Time Frame: 1hour, day 35 ]measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
- Insulin sensitivity [ Time Frame: 4hours, day 35 ]Glucose infusion rate (GIR) from the hyperinsulinemic euglycemic clamp
- Intracardiomyocellular lipid content [ Time Frame: 1hour, day 35 ]Cardiac 1H-MRS: fasted & insulin-stimulated
- Cardiac systolic function [ Time Frame: 1hour, day 35 ]Functional cardiac MRI: fasted & insulin-stimulated
- In vivo myocardial mitochondrial function (PCr/ATP ratio) [ Time Frame: 1hour, day 28 ]Cardiac 31P-MRS: fasted
- Cardiac diastolic function [ Time Frame: 1hour, day 34 ]Cardiac ultrasound
- Intrahepatic lipid content and hepatic lipid composition [ Time Frame: 1hour, day 28 ]Hepatic 1H-MRS: fasted
- Blood pressure [ Time Frame: 24hours, day 27 ]24-hour blood pressure monitor
- Whole body (sleeping) energy metabolism (sleeping energy expenditure and substrate oxidation) [ Time Frame: 12 hours, day 34 ]Respiration chamber: overnight
- Whole body maximum aerobic capacity [ Time Frame: 1hour, day 28 ]VO2 max test
- Total body mass and fat mass [ Time Frame: 0.5 hour, day 35 ]Body composition
- Ex vivo PPARalpha expression and downstream targets [ Time Frame: 0.5 hour, day 35 ]Skeletal muscle biopsy
- Postprandial lipid response [ Time Frame: 5hour, day 34 ]Meal test
- Anti-inflammatory effects (in the long term on the immune cells; acute effect on postprandial response), circadian rhythm [ Time Frame: 6hour, day 0-34-35 ]PBMC
- Cholesterol profile [ Time Frame: 5hours, day 0,7,14,21,28,35 ]Blood after venapunction
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03662984
|Contact: Vera de Wit-Verheggen, MDfirstname.lastname@example.org|
|Nutrition and Movement Sciences||Recruiting|
|Maastricht, Limburg, Netherlands, 6200MD|
|Contact: P Schrauwen, Prof 0031433882222 email@example.com|
|Principal Investigator:||Patrick Schrauwen, Professor||Maastricht University|