Ciprofibrate and Pre-diabetes

NCT03662984 | Completed Phase 3 DMC

• 1 other identifier: NL.ABR.65583
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myocardial Insulin Sensitivity; Impaired Glucose Metabolism; Diastolic Dysfunction

Outcome Measures

Primary Outcomes (1)

• Myocardial insulin sensitivity

  measured by the insulin-stimulated myocardial glucose uptake by FDG-PET

  1hour, day 35

Secondary Outcomes (17)

• Hepatic glucose uptake

  1hour, day 35

• Skeletal muscle glucose uptake

  1hour, day 35

• Brown adipose tissue (BAT) glucose uptake

  1hour, day 35

• Insulin sensitivity

  4hours, day 35

• Intracardiomyocellular lipid content

  1hour, day 35

Study Arms (2)

Ciprofibrate

ACTIVE COMPARATOR

1dd100mg at breakfast

Drug: Ciprofibrate 100Mg Tablet

Placebo

PLACEBO COMPARATOR

1dd0mg at breakfast

Drug: Placebo Oral Tablet

Interventions

Ciprofibrate 100Mg Tablet DRUG

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.

Also known as: PPARa agonist

Ciprofibrate

Placebo Oral Tablet DRUG

To compare ciprofibrate

Placebo

Eligibility Criteria

• Age: 40 Years - 70 Years
• Gender Eligibility Details: Females have a oestrogen receptor which interferes with the PPARa receptor
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Maastricht University: collaborator

Study Sites (1)

Nutrition and Movement Sciences

Maastricht, Limburg, 6200MD, Netherlands

Location

Related Publications (1)

• de Wit-Verheggen VHW, Vanweert F, Raiko J, Lienard V, Schaart G, Gemmink A, Nascimento EBM, Hesselink MKC, Wildberger JE, Wierts R, Joris PJ, Haas J, Montaigne D, Staels B, Phielix E, Schrauwen P, Schrauwen-Hinderling VB, van de Weijer T. The tissue-specific metabolic effects of the PPARalpha agonist ciprofibrate in insulin-resistant male individuals: a double-blind, randomized, placebo-controlled crossover study. Obesity (Silver Spring). 2023 Oct;31(10):2493-2504. doi: 10.1002/oby.23874. Epub 2023 Sep 5.

  PMID: 37670579 DERIVED

MeSH Terms

Interventions

ciprofibrate; Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Patrick Schrauwen, Professor

  Maastricht University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2018
• First Posted: September 10, 2018
• Study Start: November 1, 2018
• Primary Completion: November 6, 2020
• Study Completion: November 13, 2020
• Last Updated: January 8, 2021

Record last verified: 2021-01

Locations

NL (1)