Cross-over Study on Effect of Lipid Lowering by Acipimox on Cardiac and Skeletal Muscle Mitochondrial Function (ACP)

May 13, 2013 updated by: Maastricht University Medical Center

The Effect of Lipid Lowering by Acipimox on Cardiac and Skeletal Muscle Mitochondrial Function

Accumulation of lipid in skeletal and cardiac muscle has been associated with insulin resistance and diabetic cardiomyopathy. In skeletal muscle, lipotoxic damage has been suggested to lead to dysfunction of mitochondria. It remains unknown whether lipotoxicity leads to mitochondrial dysfunction in heart as well, and if so, whether this also leads to cardiomyopathy (failure of the heart). Although it has been shown that lipid lowering agents can improve insulin sensitivity, the effect of lowering free fatty acids on cardiac and skeletal muscle mitochondrial function remains unknown. In this study the investigators want to investigate whether lowering cardiac and muscular lipid content will improve mitochondrial and cellular function in type 2 diabetic patients.

To this end, type 2 diabetic patients and body mass index (BMI)-matched controls will be included in a blinded cross-over design, in which subjects will receive a lipid lowering agent (Acipimox) or placebo for 2 weeks in random order. During treatment, diabetes medication will be stopped. Baseline measurements will be performed prior to the study and after each treatment to assess cardiac and muscular lipid accumulation, cardiac function, mitochondrial function and insulin sensitivity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Not Applicable

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
      • Maastricht, Netherlands, 6200MD
        • Maastricht University Medical Centre

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

Ages Eligible for Study

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or postmenopausal females
  • Age 40-70 years
  • Obese (BMI > 30 kg/m2), non-insulin dependent type 2 diabetic patients and BMI matched control subjects without diabetes.
  • Generally healthy with specifically no known cardiovascular disease, dyslipidemia, or gastric ulcers (contra-ind. of Acipimox), which can affect the study parameters.
  • Must be on sulphonylurea(SU)- derivate or metformin therapy for at least six months with a constant dose for at least two months, or on dietary treatment for at least six months
  • Well-controlled diabetes: HbA1c<8%.
  • Control subjects must have a plasma glucose lower than 6,1 mmol/L.
  • Stable dietary habits (no weight loss/gain > 3 kg in the last 6 months)

Exclusion Criteria:

  • Known cardiovascular disease, dyslipidemia, hepatic or renal failure and gastric ulcers.
  • Insulin dependent Diabetic patients.
  • Use of lipid lowering agents, except from Statins, as these do not affect triglycerides levels (with exception to Lipitor).
  • Use of Thiazolidines (glitazone/rosiglitazone/pioglitazone/troglitazone)
  • Use of anti-coagulants (not thrombocyte-aggregation inhibitors)
  • Aberrant ECG (with signs of ischemia or cardiac failure or arrythmia's)
  • Weight gain/loss > 3 kg in the last 6 months.
  • Hb < 7,3 in women, and < 7,8 in men.

  • Contraindications for MRI scans:

    • Electronic implants such as pacemakers or neurostimulator
    • Iron-containing corpora aliena in eyes or brain
    • Some hearing aids and artificial (heart) valves which are contraindicated for MRS
    • Claustrophobia
  • Subjects, who do not want to be informed about unexpected medical findings, or do not wish that their physician is informed, cannot participate in the study.

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 Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acipimox
Subjects will receive Acipimox or a placebo in random order. Acipimox is a commercially available and registrated drug, that lowers free fatty acids by inhibiting hormone sensitive lipase in the peripheral adipose tissue. No serious side-effects are known other than rare anaphylactic reactions.
Drug: Acipimox
A capsula is given with 250mg Acipimox, 3dd; 1 after each meal. This will be done during 14 days.
Other Names:
  • Olbetam
  • Nedios
Placebo Comparator: Cellulosum mycrocryst capsula
Subjects will receive Acipimox or a placebo in random order. Acipimox is a commercially available and registrated drug, that lowers free fatty acids by inhibiting hormone sensitive lipase in the peripheral adipose tissue. No serious side-effects are known other than rare anaphylactic reactions.
Drug: Cellulosum Mycrocryst
Capsule with cellulosum powder; this has to be taken 3 dd; 1 after each meal during 14 days.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
changes in mitochondrial function
Time Frame: 2 weeks
2 weeks
changes in cardiac function
Time Frame: 2 weeks
2 weeks
lipid accumulation in ectopic tissue (cardiac and skeletal muscle)
Time Frame: 2 weeks
2 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
insulin sensitivity
Time Frame: 2 weeks
2 weeks
oxidative stress markers
Time Frame: 2 weeks
2 weeks

Collaborators and Investigators

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

Sponsor

Maastricht University Medical Center

Collaborators

Center for Translational Molecular Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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

March 1, 2010

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

July 20, 2009

First Submitted That Met QC Criteria

July 20, 2009

First Posted (Estimate)

July 21, 2009

Study Record Updates

Last Update Posted (Estimate)

May 14, 2013

Last Update Submitted That Met QC Criteria

May 13, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MEC 09-3-033
  • CTMM2008172
  • EFSD10122008
  • ZonMw91896618

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.

Clinical Trials on Diabetes Mellitus, Type 2

Clinical Trials on Acipimox

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mongolia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe