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

July 20, 2009
May 13, 2013
March 2010
December 2012   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT00943059 on ClinicalTrials.gov Archive Site
  • insulin sensitivity [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • oxidative stress markers [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Cross-over Study on Effect of Lipid Lowering by Acipimox on Cardiac and Skeletal Muscle Mitochondrial Function
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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
  • Diabetes Mellitus, Type 2
  • Cardiomyopathy, Dilated
  • 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
  • Drug: Cellulosum Mycrocryst
    Capsule with cellulosum powder; this has to be taken 3 dd; 1 after each meal during 14 days.
    Other Name: Placebo
  • 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.
    Intervention: Drug: Acipimox
  • 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.
    Intervention: Drug: Cellulosum Mycrocryst

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
31
December 2012
December 2012   (final data collection date for primary outcome measure)

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.
Both
40 Years to 70 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00943059
MEC 09-3-033, CTMM2008172, EFSD10122008, ZonMw91896618
Yes
Maastricht University Medical Center
Maastricht University Medical Center
Center for Translational Molecular Medicine
Principal Investigator: Patrick Schrauwen, PhD Maastricht University Medical Centre
Maastricht University Medical Center
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP