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| Name | Class |
|---|---|
| American Diabetes Association | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acipimox | Experimental | Treatment with the study drug Acipimox |
|
| Placebo | Placebo Comparator | Treatment with Placebo control. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acipimox | Drug | 250 mg by mouth (PO) three times daily |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 to 6-months visit |
| Change From Baseline in Mitochondrial Density at 6 Months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven Grinspoon, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26691888 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Acipimox | Treatment with the study drug Acipimox Acipimox: 250 mg by mouth (PO) three times daily |
| FG001 | Placebo | Treatment with Placebo control. Placebo: 0 mg by mouth (PO) three times daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Acipimox | Treatment with the study drug Acipimox Acipimox: 250 mg by mouth (PO) three times daily |
| BG001 | Placebo | Treatment with Placebo control. Placebo: 0 mg by mouth (PO) three times daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | all available data used | Posted | Mean | Standard Deviation | mM/s | Change from Baseline to 6-months Visit |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Acipimox | Treatment with the study drug Acipimox Acipimox: 250 mg by mouth (PO) three times daily |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Flushing | Skin and subcutaneous tissue disorders | SNOMED CT | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Steven K. Grinspoon | Massachusetts General Hospital | 617-724-9109 | sgrinspoon@partners.org |
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| ID | Term |
|---|---|
| D056128 | Obesity, Abdominal |
| D007333 | Insulin Resistance |
| D015228 | Hypertriglyceridemia |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
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| ID | Term |
|---|---|
| C027696 | acipimox |
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| Drug |
0 mg by mouth (PO) three times daily |
|
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 to 6-months |
| Change From Baseline in Intramyocellular Lipid Content at 6-months | Change in tibialis intramyocellular lipid (IMCL) normalized to creatinine is given. | Change from Baseline to 6-months |
| Change From Baseline in Lipid Profile at 6-months | Change in direct low density lipoprotein (LDL) cholesterol is given | Change from Baseline to 6-months |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
Treatment with Placebo control.
Placebo: 0 mg by mouth (PO) three times daily
|
|
|
| Secondary | 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. | all available data used | Posted | Mean | Standard Deviation | mg/kg/min | Change from Baseline to 6-months visit |
|
|
|
|
| Secondary | 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. | all available data used | Posted | Mean | Standard Deviation | percentage of total muscle fiber area | Change from Baseline to 6-months |
|
|
|
|
| Secondary | Change From Baseline in Intramyocellular Lipid Content at 6-months | Change in tibialis intramyocellular lipid (IMCL) normalized to creatinine is given. | all available data used | Posted | Mean | Standard Deviation | ratio of IMCL peak to Creatinine peak | Change from Baseline to 6-months |
|
|
|
|
| Secondary | Change From Baseline in Lipid Profile at 6-months | Change in direct low density lipoprotein (LDL) cholesterol is given | all available data used | Posted | Mean | Standard Deviation | mg/dL | Change from Baseline to 6-months |
|
|
|
|
| 0 |
| 20 |
| 16 |
| 20 |
| EG001 | Placebo | Treatment with Placebo control. Placebo: 0 mg by mouth (PO) three times daily | 0 | 19 | 16 | 19 |
| nausea | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
|
| Dizziness | General disorders | SNOMED CT | Non-systematic Assessment |
|
| abdominal bloating | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
|
| dry mouth | General disorders | SNOMED CT | Non-systematic Assessment |
|
| gastroesophageal reflux | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
|
| pain following biopsy | Surgical and medical procedures | SNOMED CT | Non-systematic Assessment |
|
| bleeding following biopsy | Surgical and medical procedures | SNOMED CT | Non-systematic Assessment |
|
| abdominal pain | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
|
| vomiting | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
|
| joint pain and swelling | Musculoskeletal and connective tissue disorders | SNOMED CT | Non-systematic Assessment |
|
| constipation | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
|
| rash | Skin and subcutaneous tissue disorders | SNOMED CT | Non-systematic Assessment |
|
| loss of appetite | General disorders | SNOMED CT | Non-systematic Assessment |
|
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| D009750 |
| Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |