Effects of Acipimox on Mitochondrial Function in Obesity

NCT01488409 | Completed Phase 2 Results DMC

• 1 other identifier: 2011-P-000175
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Phosphocreatine Recovery (ViPCr) at 6-months

  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.

  Change from Baseline to 6-months Visit

Secondary Outcomes (4)

• Change From Baseline in Insulin Sensitivity at 6-months

  Change from Baseline to 6-months visit

• Change From Baseline in Mitochondrial Density at 6 Months

  Change from Baseline to 6-months

• Change From Baseline in Intramyocellular Lipid Content at 6-months

  Change from Baseline to 6-months

• Change From Baseline in Lipid Profile at 6-months

  Change from Baseline to 6-months

Study Arms (2)

Acipimox

EXPERIMENTAL

Treatment with the study drug Acipimox

Drug: Acipimox

Placebo

PLACEBO COMPARATOR

Treatment with Placebo control.

Drug: Placebo

Interventions

Acipimox DRUG

250 mg by mouth (PO) three times daily

Acipimox

Placebo DRUG

0 mg by mouth (PO) three times daily

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women age 18-55 years old
• Body Mass Index (BMI) ≥ 30 kg/m2
• Waist circumference ≥ 102 cm in men and ≥ 88 cm in women
• 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.

You may not qualify if:

• 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.
• Subjects who have a known history of diabetes, using any anti-diabetic drugs, or fasting blood glucose of ≥ 125 mg/dl.
• Use of cholesterol lowering medication including niacin or fish oil.
• Changes in anti-hypertensive regimen within 3months of screening.
• 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).
• Use of Aspirin, Clopidogrel (Plavix), Warfarin (Coumadin) or other anti-coagulants
• History of or active peptic ulcer disease
• 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
• Subjects with contraindication for an MRI study including any significant metal in their body including surgical clippings, or pacemakers and known claustrophobia.
• History of recent alcohol or substance abuse (\< 1 year)
• Positive pregnancy test or lactating females
• 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
• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• American Diabetes Association: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 26691888 DERIVED

MeSH Terms

Conditions

Obesity, Abdominal; Insulin Resistance; Hypertriglyceridemia

Interventions

acipimox

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders

Results Point of Contact

• Title: Steven K. Grinspoon
• Organization: Massachusetts General Hospital

sgrinspoon@partners.org

617-724-9109

Study Officials

• Steven Grinspoon, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 2, 2011
• First Posted: December 8, 2011
• Study Start: May 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: March 1, 2016
• Results First Posted: February 3, 2016

Record last verified: 2016-02

Locations

US (1)