Effects of Acipimox on Mitochondrial Function in Obesity

NCT ID: NCT01488409

Last Updated: 2016-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2015-01-31

Brief Summary

The purpose of the study is to examine whether a medication called acipimox can improve your body's mitochondria. Mitochondria are the "power house" of the cell and make energy for your body.

Obesity is associated with increased risk for developing diabetes. However, the investigators do not know how obesity leads to diabetes. Previous studies have shown levels of fat in the blood (free fatty acids or FFA) are higher in obesity, and elevated FFA can affect how our body uses glucose and responds to insulin. Recent studies have shown that changes in mitochondria may be involved in the development of diabetes and may be affected by FFA. The investigators propose to improve the function of mitochondria in obese people with pre-diabetes by treating with acipimox, a medication which decreases FFA. The investigators will use state of the art techniques to evaluate the mitochondria, including a new magnetic resonance imaging (MRI) technique to measure function of mitochondria in muscle.

Conditions

Abdominal Obesity; Insulin Resistance; Hypertriglyceridemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Acipimox

Treatment with the study drug Acipimox

Group Type: EXPERIMENTAL

Acipimox

Intervention Type: DRUG

250 mg by mouth (PO) three times daily

Placebo

Treatment with Placebo control.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0 mg by mouth (PO) three times daily

Interventions

Acipimox

250 mg by mouth (PO) three times daily

Intervention Type: DRUG

Placebo

0 mg by mouth (PO) three times daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Men and women age 18-55 years old

2. Body Mass Index (BMI) ≥ 30 kg/m2

3. Waist circumference ≥ 102 cm in men and ≥ 88 cm in women

4. Hypertriglyceridemia defined as triglycerides ≥ 150 mg/dl OR Insulin resistance defined as elevated fasting glucose (≥ 100 mg/dl but <125 mg/dl) or hyperinsulinemia defined as fasting serum insulin ≥ 10 uU/ml.

Exclusion Criteria

1. Subjects on any hormonal treatment including estrogen, hormone replacement therapy, oral contraceptives, testosterone, glucocorticoids, anabolic steroids, GH, GH releasing hormone or Insulin like growth factor (IGF)-1 within 3months of enrollment.

2. Subjects who have a known history of diabetes, using any anti-diabetic drugs, or fasting blood glucose of ≥ 125 mg/dl.

3. Use of cholesterol lowering medication including niacin or fish oil.

4. Changes in anti-hypertensive regimen within 3months of screening.

5. Chronic illness including HIV, anemia (Hgb <12 g/dL), chronic kidney disease (Creatinine > 2 mg/dL), or liver disease (SGOT > 2.5 x upper limit normal).

6. Use of Aspirin, Clopidogrel (Plavix), Warfarin (Coumadin) or other anti-coagulants

7. History of or active peptic ulcer disease

8. History of any recent cardiovascular event including myocardial infarction (MI; heart attack), cerebral vascular accident (CVA; or stroke) or transient ischemic attack (TIA; or mini-stroke) within 3 months of screening visit, unstable angina pectoris, oxygen-dependent severe pulmonary disease

9. Subjects with contraindication for an MRI study including any significant metal in their body including surgical clippings, or pacemakers and known claustrophobia.

10. History of recent alcohol or substance abuse (< 1 year)

11. Positive pregnancy test or lactating females

12. Women of child-bearing potential not currently using non-hormonal birth control methods including barrier methods (intra-uterine device or IUD, condoms, diaphragms) or abstinence

13. Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Steven K. Grinspoon, MD

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven Grinspoon, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

Makimura H, Stanley TL, Suresh C, De Sousa-Coelho AL, Frontera WR, Syu S, Braun LR, Looby SE, Feldpausch MN, Torriani M, Lee H, Patti ME, Grinspoon SK. Metabolic Effects of Long-Term Reduction in Free Fatty Acids With Acipimox in Obesity: A Randomized Trial. J Clin Endocrinol Metab. 2016 Mar;101(3):1123-33. doi: 10.1210/jc.2015-3696. Epub 2015 Dec 21.

Reference Type: DERIVED

PMID: 26691888 (View on PubMed)

Other Identifiers

2011-P-000175

Identifier Type: -

Identifier Source: org_study_id