Ciprofibrate and Pre-diabetes (FIT)

January 7, 2021 updated by: Maastricht University Medical Center

Effects of Ciprofibrate on Myocardial Insulin Sensitivity in Pre-diabetes

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands, 6200MD
        • Nutrition and Movement Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • PPARa agonist
PLACEBO_COMPARATOR: Placebo
1dd0mg at breakfast
Drug: Placebo Oral Tablet
To compare ciprofibrate

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Myocardial insulin sensitivity
Time Frame: 1hour, day 35
measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
1hour, day 35

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hepatic glucose uptake
Time Frame: 1hour, day 35
measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
1hour, day 35
Skeletal muscle glucose uptake
Time Frame: 1hour, day 35
measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
1hour, day 35
Brown adipose tissue (BAT) glucose uptake
Time Frame: 1hour, day 35
measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
1hour, day 35
Insulin sensitivity
Time Frame: 4hours, day 35
Glucose infusion rate (GIR) from the hyperinsulinemic euglycemic clamp
4hours, day 35
Intracardiomyocellular lipid content
Time Frame: 1hour, day 35
Cardiac 1H-MRS: fasted & insulin-stimulated
1hour, day 35
Cardiac systolic function
Time Frame: 1hour, day 35
Functional cardiac MRI: fasted & insulin-stimulated
1hour, day 35
In vivo myocardial mitochondrial function (PCr/ATP ratio)
Time Frame: 1hour, day 28
Cardiac 31P-MRS: fasted
1hour, day 28
Cardiac diastolic function
Time Frame: 1hour, day 34
Cardiac ultrasound
1hour, day 34
Intrahepatic lipid content and hepatic lipid composition
Time Frame: 1hour, day 28
Hepatic 1H-MRS: fasted
1hour, day 28
Blood pressure
Time Frame: 24hours, day 27
24-hour blood pressure monitor
24hours, day 27
Whole body (sleeping) energy metabolism (sleeping energy expenditure and substrate oxidation)
Time Frame: 12 hours, day 34
Respiration chamber: overnight
12 hours, day 34
Whole body maximum aerobic capacity
Time Frame: 1hour, day 28
VO2 max test
1hour, day 28
Total body mass and fat mass
Time Frame: 0.5 hour, day 35
Body composition
0.5 hour, day 35
Ex vivo PPARalpha expression and downstream targets
Time Frame: 0.5 hour, day 35
Skeletal muscle biopsy
0.5 hour, day 35
Postprandial lipid response
Time Frame: 5hour, day 34
Meal test
5hour, day 34
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
6hour, day 0-34-35
Cholesterol profile
Time Frame: 5hours, day 0,7,14,21,28,35
Blood after venapunction
5hours, day 0,7,14,21,28,35

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Maastricht University Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Maastricht University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Patrick Schrauwen, Professor, Maastricht University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2018

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 6, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 13, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 29, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 8, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL.ABR.65583

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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