Effects of Acipimox on Mitochondrial Function in Obesity

Phase 2

Completed

• Conditions: Insulin Resistance; Abdominal Obesity; Hypertriglyceridemia
• Interventions: Drug: Acipimox; Drug: Placebo

• Registration Number: NCT01488409
• Lead Sponsor: Massachusetts General Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-12-02
• Study First Submitted QC: 2011-12-06
• Study First Posted: 2011-12-08
• Study Start: 2012-05
• Primary Completion: 2015-01
• Study Completion: 2015-01
• Results First Submitted: 2016-01-04
• Results First Submitted QC: 2016-01-04
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-02
• Results First Posted: 2016-02-03
• Last Update Posted: 2016-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acipimox	Acipimox	Treatment with the study drug Acipimox
Placebo	Placebo	Treatment with Placebo control.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Phosphocreatine Recovery (ViPCr) at 6-months	Change from Baseline to 6-months Visit	The rate of recovery of phosphocreatine concentration after depletion by exercise is considered a measurement of mitochondrial function. Change in phosphocreatine recovery from baseline to 6 months will therefore give a measurement of change in mitochondrial function. ViPCR is given -- a higher value indicates better mitochondrial function.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mitochondrial Density at 6 Months	Change from Baseline to 6-months	Muscle tissue obtained from biopsy will be used to assess mitochondrial number and morphology by microscopes at Baseline and at 6-months. The change in mitochondrial density from 6 months to baseline is given.
Change From Baseline in Insulin Sensitivity at 6-months	Change from Baseline to 6-months visit	Change in insulin resistance assessed by hyperinsulinemic-euglycemic clamp study at Baseline and at 6-months. Change in insulin-stimulated glucose uptake (M) during 40 mU/m2/min insulin clamp is given.
Change From Baseline in Intramyocellular Lipid Content at 6-months	Change from Baseline to 6-months	Change in tibialis intramyocellular lipid (IMCL) normalized to creatinine is given.
Change From Baseline in Lipid Profile at 6-months	Change from Baseline to 6-months	Change in direct low density lipoprotein (LDL) cholesterol is given

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States