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| ID | Type | Description | Link |
|---|---|---|---|
| P20HL113444-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Leducq Foundation | OTHER |
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This study will test whether lowering the delivery of excess fats to the heart in persons with type-2 diabetes mellitus improves heart muscle function. The investigators will also test whether specific lipid molecular species in plasma can serve as biomarkers for diabetic heart disease.
Screening procedures include 12-hour fasting blood draw, urine pregnancy testing for females, completion of medical history questionnaire, and stress echocardiography to rule out coronary artery disease or cardiomyopathy.
Subjects who meet screening criteria will return for visit 2, which consists of a urine collection, 12-hour fasting blood draw, dual-energy X-ray absorptiometry (DXA) for body composition, magnetic resonance spectroscopy analysis of the liver, and resting echocardiogram for analysis of heart structure and function. Subjects will then be randomized to treatment with fenofibrate (160 mg/d) or an identical-appearing placebo for 12 weeks. They will be asked to continue their usual medications, diet and physical activity. Subjects will receive a pedometer to wear daily to track their physical activity. Subjects will meet with dietitians from the Lifestyle Intervention Core to complete a 24-hour dietary recall. They will be instructed to record their daily blood glucose concentrations, distance walked and any side effects, illnesses or stresses in a study-supplied log. Subjects will be instructed to either email or fax the log to the study coordinator each week (or discuss by phone).
Subjects will return 6 weeks after starting intervention for visit 3 to ensure their medical safety. Procedures at this visit include an interim medical history, urine pregnancy test for females, blood draw to rule out untoward effects of the study drug on liver or kidney function, pill count to assess compliance, review of logs of blood glucose, distance walked, and side effects, illnesses or stresses, and meeting with a dietitian for a 24-hour dietary recall.
Subjects will continue to take their study medication/placebo and keep logs of blood glucose levels, distance walked, and side effects, illnesses and stresses for another 6 weeks. They will return for visit 4 after 12 total weeks of intervention. Visit 4 involves a urine collection, 12-hour fasting blood draw, review of subject logs, pill count, and 24-hour dietary recall. In addition, magnetic resonance spectroscopy analysis of the liver and resting echocardiogram analysis of the heart will be performed to determine if there have been any changes in liver fat or heart function during the 12-week intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fenofibrate | Experimental | One fenofibrate 160 mg capsule per day for 12 weeks |
|
| Placebo for fenofibrate | Placebo Comparator | One inert sugar pill per day for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fenofibrate | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cardiac Diastolic Function as Measured by E' (cm/s) | Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline. | Baseline and 12 weeks |
| Change in Cardiac Systolic Function as Measured by Fractional Shortening Percent | Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline. | Baseline and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in C24:0/C16:0 Ceramide Ratio | Mass spectrometry-based quantification of the ratio of C24:0 ceramide to C16:0 ceramide in plasma. | Baseline and 12 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean E Schaffer, MD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 4835750 | Background | Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974 Jul;34(1):29-34. doi: 10.1016/0002-9149(74)90089-7. No abstract available. | |
| 4278055 | Background | Hamby RI, Zoneraich S, Sherman L. Diabetic cardiomyopathy. JAMA. 1974 Sep 23;229(13):1749-54. No abstract available. |
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Potential subjects were given the approved consent form to consider. If interested, they were scheduled for a screening visit in the Center for Applied Research Sciences. The consent form was signed before any testing took place. Blood and urine were collected and a cardiac stress test was performed to evaluate the subject for eligibility.
Subjects were recruited from clinics, practices and laboratories within the Barnes-Jewish Hospital consortium, Volunteer for Health and Diabetes Research Connections recruitment programs at Washington University School of Medicine, and through local advertisements, posters, emails and flyers. Dates of recruitment were from May 2013 to October 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Fenofibrate | Participants were instructed to take one fenofibrate 160 mg capsule every day for 12 weeks Fenofibrate |
| FG001 | Placebo for Fenofibrate | Participants were instructed to take one inert sugar pill every day for 12 weeks Placebo for fenofibrate |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Fenofibrate | One fenofibrate 160 mg capsule per day for 12 weeks Fenofibrate |
| BG001 | Placebo for Fenofibrate | One inert sugar pill per day for 12 weeks Placebo for fenofibrate |
| 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 in Cardiac Diastolic Function as Measured by E' (cm/s) | Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline. | All participants for whom E' (diastolic function) was measured at baseline and 12 weeks. | Posted | Mean | Standard Deviation | cm/s | Baseline and 12 weeks |
|
Adverse event data were collected during the 12 weeks of intervention.
Participants self-reported side-effects weekly during intervention, and an interim study visit took place half-way through the 12 weeks so safety labs could be obtained.
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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 | Fenofibrate | Participants were instructed to take one fenofibrate 160 mg capsule every day for 12 weeks Fenofibrate |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| rash/itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
Findings of this study cannot be extended to those who do not fit the entry criteria. Also, since this was a targeted lipidomics study, there may be changes in other lipid species after treatment with fenofibrate that were not analyzed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jean E. Schaffer, MD | Washington University School of Medicine | 314-362-8717 | jschaff@wustl.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 22, 2017 | Jan 31, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 1, 2019 | Feb 1, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D058065 | Diabetic Cardiomyopathies |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D011345 | Fenofibrate |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D058607 | Fibric Acids |
| D058610 | Isobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
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| Placebo for fenofibrate |
| Drug |
|
|
| 15123530 | Background | Peterson LR, Herrero P, Schechtman KB, Racette SB, Waggoner AD, Kisrieva-Ware Z, Dence C, Klein S, Marsala J, Meyer T, Gropler RJ. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation. 2004 May 11;109(18):2191-6. doi: 10.1161/01.CIR.0000127959.28627.F8. Epub 2004 May 3. |
| 16458143 | Background | Herrero P, Peterson LR, McGill JB, Matthew S, Lesniak D, Dence C, Gropler RJ. Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. J Am Coll Cardiol. 2006 Feb 7;47(3):598-604. doi: 10.1016/j.jacc.2005.09.030. Epub 2006 Jan 18. |
| 12594743 | Background | Szczepaniak LS, Dobbins RL, Metzger GJ, Sartoni-D'Ambrosia G, Arbique D, Vongpatanasin W, Unger R, Victor RG. Myocardial triglycerides and systolic function in humans: in vivo evaluation by localized proton spectroscopy and cardiac imaging. Magn Reson Med. 2003 Mar;49(3):417-23. doi: 10.1002/mrm.10372. |
| 15522914 | Background | Sharma S, Adrogue JV, Golfman L, Uray I, Lemm J, Youker K, Noon GP, Frazier OH, Taegtmeyer H. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J. 2004 Nov;18(14):1692-700. doi: 10.1096/fj.04-2263com. |
| Background | Griffin JA, Osborn BW, Smithline HA. The impact of diabetes on hospital admissions, length of stay and mortality in emergency department patients with acute decompensated heart failure without ischemia. Acad Emerg Med. 2005;12:s97 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Cardiac Diastolic Function (E') | Study-specific baseline characteristics were determined for subjects who completed the 12-week intervention only. | Mean | Standard Deviation | cm/s |
|
| Cardiac Systolic Function (Fractional Shortening) | Study-specific baseline characteristics were determined for subjects who completed the 12-week intervention only. | Mean | Standard Deviation | percent |
|
| C24:0/C16:0 ceramides | Study-specific baseline characteristics were determined for subjects who completed the 12-week intervention only. | Mean | Standard Deviation | ratio |
|
|
|
|
| Primary | Change in Cardiac Systolic Function as Measured by Fractional Shortening Percent | Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline. | All participants for whom fractional shortening was measured at baseline and 12 weeks. | Posted | Mean | Standard Deviation | percent | Baseline and 12 weeks |
|
|
|
|
| Secondary | Change in C24:0/C16:0 Ceramide Ratio | Mass spectrometry-based quantification of the ratio of C24:0 ceramide to C16:0 ceramide in plasma. | All participants for whom C24:0 and C16:0 ceramides were measured at baseline and 12 weeks. | Posted | Mean | Standard Deviation | ratio | Baseline and 12 weeks |
|
|
|
|
| 0 |
| 34 |
| 0 |
| 34 |
| 2 |
| 34 |
| EG001 | Placebo for Fenofibrate | Participants were instructed to take one inert sugar pill every day for 12 weeks Placebo for fenofibrate | 0 | 36 | 0 | 36 | 0 | 36 |
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| D009202 | Cardiomyopathies |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010647 | Phenyl Ethers |
| D004987 | Ethers |
| D001577 | Benzophenones |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010636 | Phenols |
| D007659 | Ketones |
| D002241 | Carbohydrates |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Two-sample t-test was used to compare baseline mean values of biomarkers. All statistical tests are two-sided at significance level 0.05. |
Two-sample t-test was used to compare baseline mean values of biomarkers. All statistical tests are two-sided at significance level 0.05. |