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Effects of Acipimox on Mitochondrial Function in Obesity

This study is currently recruiting participants.
Verified May 2013 by Massachusetts General Hospital
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Hideo Makimura, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01488409
First received: December 2, 2011
Last updated: May 28, 2013
Last verified: May 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Abdominal Obesity
Insulin Resistance
Hypertriglyceridemia
 Drug: Acipimox
Drug: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of Short Term Acipimox Treatment on Skeletal Muscle Phosphocreatine Recovery in Obesity

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change from Baseline in Phosphocreatine recovery at 6-months [ Time Frame: Change from Baseline to 6-months Visit ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change from Baseline in insulin sensitivity at 6-months [ Time Frame: Change from Baseline to 6-months visit ] [ Designated as safety issue: No ]
    Change in insulin resistance assessed by 2-step hyperinsulinemic-euglycemic clamp study at Baseline and at 6-months.

  • Change from Baseline in mitochondrial gene expression at 6-months [ Time Frame: Change from Baseline to 6-months ] [ Designated as safety issue: No ]
    Muscle biopsies will be performed and small pieces of muscle tissue will be used to measure expression of genes involved in mitochondrial function and biogenesis at Baseline and at 6-months

  • Change from Baseline in mitochondrial number and morphology at 6-months [ Time Frame: Change from Baseline to 6-months ] [ Designated as safety issue: No ]
    Muscle tissue obtained from biopsy will be used to assess mitochondrial number and morphology by microscopes at Baseline and at 6-months

  • Change from Baseline in intramyocellular lipid content at 6-months [ Time Frame: Change from Baseline to 6-months ] [ Designated as safety issue: No ]
  • Change from Baseline in lipid profile at 3-months and 6-months [ Time Frame: Change from Baseline to 3-months and 6-months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: May 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acipimox
Treatment with the study drug Acipimox
 Drug: Acipimox
250 mg by mouth (PO) three times daily
Placebo Comparator: Placebo
Treatment with Placebo control.
 Drug: Placebo
0 mg by mouth (PO) three times daily

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01488409

Contacts
Contact: Hideo Makimura, MD, PhD 617-726-8277 hmakimura@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Hideo Makimura, MD, PhD     617-726-8277     hmakimura@partners.org    
Principal Investigator: Hideo Makimura, MD, PhD            
Sponsors and Collaborators
Massachusetts General Hospital
American Diabetes Association
Investigators
Principal Investigator: Hideo Makimura, MD, PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Hideo Makimura, Assistant Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01488409     History of Changes
Other Study ID Numbers: 2011-P-000175
Study First Received: December 2, 2011
Last Updated: May 28, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertriglyceridemia
Insulin Resistance
Obesity
Obesity, Abdominal
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Overnutrition
 Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Acipimox
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013