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

Sponsors

Lead Sponsor: Maastricht University Medical Center

Collaborator: Center for Translational Molecular Medicine

Source Maastricht University Medical Center
Brief Summary

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.

Overall Status Completed
Start Date March 2010
Completion Date December 2012
Primary Completion Date December 2012
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
changes in mitochondrial function 2 weeks
changes in cardiac function 2 weeks
lipid accumulation in ectopic tissue (cardiac and skeletal muscle) 2 weeks
Secondary Outcome
Measure Time Frame
insulin sensitivity 2 weeks
oxidative stress markers 2 weeks
Enrollment 31
Condition
Intervention

Intervention Type: Drug

Intervention Name: Acipimox

Description: A capsula is given with 250mg Acipimox, 3dd; 1 after each meal. This will be done during 14 days.

Arm Group Label: Acipimox

Intervention Type: Drug

Intervention Name: Cellulosum Mycrocryst

Description: Capsule with cellulosum powder; this has to be taken 3 dd; 1 after each meal during 14 days.

Arm Group Label: Cellulosum mycrocryst capsula

Other Name: Placebo

Eligibility

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.

Gender: All

Minimum Age: 40 Years

Maximum Age: 70 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Patrick Schrauwen, PhD Principal Investigator Maastricht University Medical Centre
Location
Facility: Maastricht University Medical Centre
Location Countries

Netherlands

Verification Date

May 2013

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Acipimox

Type: Experimental

Description: 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.

Label: Cellulosum mycrocryst capsula

Type: Placebo Comparator

Description: 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.

Acronym ACP
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Basic Science

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov