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Effects of Acipimox on Mitochondrial Function in Obesity

Primary Purpose

Abdominal Obesity, Insulin Resistance, Hypertriglyceridemia

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Acipimox

Placebo

About this trial

This is an interventional treatment trial for Abdominal Obesity

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Acipimox

Placebo

Arm Description

Treatment with the study drug Acipimox

Treatment with Placebo control.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change From Baseline in Insulin Sensitivity at 6-months

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 Mitochondrial Density at 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 Intramyocellular Lipid Content at 6-months

Change in tibialis intramyocellular lipid (IMCL) normalized to creatinine is given.

Change From Baseline in Lipid Profile at 6-months

Change in direct low density lipoprotein (LDL) cholesterol is given

Full Information

NCT ID

NCT01488409

First Posted

December 2, 2011

Last Updated

February 2, 2016

Sponsor

Massachusetts General Hospital

Collaborators

American Diabetes Association

1. Study Identification

Unique Protocol Identification Number

NCT01488409

Brief Title

Effects of Acipimox on Mitochondrial Function in Obesity

Official Title

The Effects of Short Term Acipimox Treatment on Skeletal Muscle Phosphocreatine Recovery in Obesity

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Completed

Study Start Date

May 2012 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

American Diabetes Association

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Abdominal Obesity, Insulin Resistance, Hypertriglyceridemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Acipimox

Arm Type

Experimental

Arm Description

Treatment with the study drug Acipimox

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Treatment with Placebo control.

Intervention Type

Drug

Intervention Name(s)

Acipimox

Intervention Description

250 mg by mouth (PO) three times daily

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

0 mg by mouth (PO) three times daily

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Change from Baseline to 6-months Visit

Secondary Outcome Measure Information:

Title

Change From Baseline in Insulin Sensitivity at 6-months

Description

Time Frame

Change from Baseline to 6-months visit

Title

Change From Baseline in Mitochondrial Density at 6 Months

Description

Time Frame

Change from Baseline to 6-months

Title

Change From Baseline in Intramyocellular Lipid Content at 6-months

Description

Change in tibialis intramyocellular lipid (IMCL) normalized to creatinine is given.

Time Frame

Change from Baseline to 6-months

Title

Change From Baseline in Lipid Profile at 6-months

Description

Change in direct low density lipoprotein (LDL) cholesterol is given

Time Frame

Change from Baseline to 6-months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven Grinspoon, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

26691888

Citation

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.

Results Reference

derived

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Effects of Acipimox on Mitochondrial Function in Obesity

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