Text Size

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

This study has been completed.
Sponsor:
Collaborator:
Center for Translational Molecular Medicine
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT00943059
First received: July 20, 2009
Last updated: May 13, 2013
Last verified: May 2013
History of Changes
  Purpose

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.


Condition Intervention
Diabetes Mellitus, Type 2
Cardiomyopathy, Dilated
 Drug: Acipimox
Drug: Cellulosum Mycrocryst

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: The Effect of Lipid Lowering by Acipimox on Cardiac and Skeletal Muscle Mitochondrial Function

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • changes in mitochondrial function [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • changes in cardiac function [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • lipid accumulation in ectopic tissue (cardiac and skeletal muscle) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • insulin sensitivity [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • oxidative stress markers [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 31
Study Start Date: March 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Placebo

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00943059

Locations
Netherlands
Maastricht University Medical Centre
Maastricht, Netherlands, 6200MD
Sponsors and Collaborators
Maastricht University Medical Center
Center for Translational Molecular Medicine
Investigators
Principal Investigator: Patrick Schrauwen, PhD Maastricht University Medical Centre
  More Information

Additional Information:
Website of location of trail.  This link exits the ClinicalTrials.gov site
Website of department of Human Biology, who conduct trail.  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT00943059     History of Changes
Other Study ID Numbers: MEC 09-3-033, CTMM2008172, EFSD10122008, ZonMw91896618
Study First Received: July 20, 2009
Last Updated: May 13, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:
Mitochondrial function
Diabetes
Cardiomyopathy
insulin resistance
 lipid lowering
triglycerides
Acipimox

Additional relevant MeSH terms:
Cardiomyopathy, Dilated
Diabetes Mellitus
Diabetes Mellitus, Type 2
Cardiomyopathies
Cardiomegaly
Heart Diseases
Cardiovascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
 Endocrine System Diseases
Acipimox
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013