Myocardial Insulin SensitivityPhase 3FITNCT03662984
Ciprofibrate and Pre-diabetes
A Phase 3 study testing Ciprofibrate 100Mg Tablet in people with Myocardial Insulin Sensitivity and Impaired Glucose Metabolism, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 70 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Myocardial Insulin Sensitivity, Impaired Glucose Metabolism, Diastolic Dysfunction
- What is being tested?
- Ciprofibrate 100Mg Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Nov 2018to 13 Nov 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Nutrition and Movement Sciences
Maastricht, Limburg, 6200MD
About this study
Official title: 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.
Read the 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.
- Being tested
- Ciprofibrate 100Mg Tablet, Placebo Oral Tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ciprofibrate 100Mg TabletDrug
Also called PPARa agonist
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.
Placebo Oral TabletDrug
To compare ciprofibrate
| Study group | Role | What they receive |
|---|---|---|
| Ciprofibrate | Active comparator | 1dd100mg at breakfast Receives: Drug: Ciprofibrate 100Mg Tablet |
| Placebo | Placebo comparator | 1dd0mg at breakfast Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial insulin sensitivity
measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
Measured: 1hour, day 35
Secondary outcomes (17)
Hepatic glucose uptake
measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
Measured: 1hour, day 35
Skeletal muscle glucose uptake
measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
Measured: 1hour, day 35
Brown adipose tissue (BAT) glucose uptake
measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
Measured: 1hour, day 35
Insulin sensitivity
Glucose infusion rate (GIR) from the hyperinsulinemic euglycemic clamp
Measured: 4hours, day 35
Intracardiomyocellular lipid content
Cardiac 1H-MRS: fasted \& insulin-stimulated
Measured: 1hour, day 35
Cardiac systolic function
Functional cardiac MRI: fasted \& insulin-stimulated
Measured: 1hour, day 35
In vivo myocardial mitochondrial function (PCr/ATP ratio)
Cardiac 31P-MRS: fasted
Measured: 1hour, day 28
Cardiac diastolic function
Cardiac ultrasound
Measured: 1hour, day 34
Intrahepatic lipid content and hepatic lipid composition
Hepatic 1H-MRS: fasted
Measured: 1hour, day 28
Blood pressure
24-hour blood pressure monitor
Measured: 24hours, day 27
Whole body (sleeping) energy metabolism (sleeping energy expenditure and substrate oxidation)
Respiration chamber: overnight
Measured: 12 hours, day 34
Whole body maximum aerobic capacity
VO2 max test
Measured: 1hour, day 28
Total body mass and fat mass
Body composition
Measured: 0.5 hour, day 35
Ex vivo PPARalpha expression and downstream targets
Skeletal muscle biopsy
Measured: 0.5 hour, day 35
Postprandial lipid response
Meal test
Measured: 5hour, day 34
Anti-inflammatory effects (in the long term on the immune cells; acute effect on postprandial response), circadian rhythm
PBMC
Measured: 6hour, day 0-34-35
Cholesterol profile
Blood after venapunction
Measured: 5hours, day 0,7,14,21,28,35
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2018
- Study start1 Nov 2018
- Primary completion6 Nov 2020
- Study completion13 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial Insulin SensitivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University
- Responsible party
- Sponsor
- Investigators
- Patrick Schrauwen, Professor, Principal investigator, Maastricht University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03662984
- Sponsor's protocol ID
- NL.ABR.65583
- Acronym
- FIT
- Status last verified
- Jan 2021
- First submitted
- 29 Aug 2018
- Last updated
- 8 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 37670579
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Ciprofibrate on Myocardial Insulin Sensitivity in Pre-diabetes
- ClinicalTrials.gov ID
- NCT03662984
- Acronym / sponsor ID
- FIT / NL.ABR.65583
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Maastricht University
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 6 Nov 2020 (actual)
- Study completion
- 13 Nov 2020 (actual)
- First posted
- 10 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ciprofibrate | Active comparator | Drug: Ciprofibrate 100Mg Tablet1dd100mg at breakfast |
| Placebo | Placebo comparator | Drug: Placebo Oral Tablet1dd0mg at breakfast |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ciprofibrate 100Mg TabletAlso: PPARa agonistCiprofibrate 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. | Drug | Ciprofibrate |
| Placebo Oral TabletTo compare ciprofibrate | Drug | Placebo |
Primary outcome
Myocardial insulin sensitivity
Time frame: 1hour, day 35
measured by the insulin-stimulated myocardial glucose uptake by FDG-PET
17 secondary outcomes
Hepatic glucose uptake
Time frame: 1hour, day 35
Skeletal muscle glucose uptake
Time frame: 1hour, day 35
Brown adipose tissue (BAT) glucose uptake
Time frame: 1hour, day 35
Insulin sensitivity
Time frame: 4hours, day 35
Intracardiomyocellular lipid content
Time frame: 1hour, day 35
Cardiac systolic function
Time frame: 1hour, day 35
In vivo myocardial mitochondrial function (PCr/ATP ratio)
Time frame: 1hour, day 28
Cardiac diastolic function
Time frame: 1hour, day 34
Intrahepatic lipid content and hepatic lipid composition
Time frame: 1hour, day 28
Blood pressure
Time frame: 24hours, day 27
Whole body (sleeping) energy metabolism (sleeping energy expenditure and substrate oxidation)
Time frame: 12 hours, day 34
Whole body maximum aerobic capacity
Time frame: 1hour, day 28
Total body mass and fat mass
Time frame: 0.5 hour, day 35
Ex vivo PPARalpha expression and downstream targets
Time frame: 0.5 hour, day 35
Postprandial lipid response
Time frame: 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
Cholesterol profile
Time frame: 5hours, day 0,7,14,21,28,35
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2021.
- Derived from this study: PubMed 37670579de 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.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Schrauwen, Professor principal investigator
Maastricht University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ciprofibrate 100Mg Tablet in people with Myocardial Insulin Sensitivity and Impaired Glucose Metabolism, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Myocardial insulin sensitivity (time frame: 1hour, day 35). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03662984, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2021.