Clinical trial NCT01752842: Lipid Biomarkers for Diabetic Heart Disease
Official title: Lipid Biomarkers for Diabetic Heart Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type II Diabetes Mellitus
Diabetes Complications
Keywords: Diabetes
Diabetic Cardiomyopathy
Triglycerides
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Leducq Foundation
First posted: 2012-12-19
Enrollment: 70
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes mellitus

Exclusion Criteria:

* body weight \> 300 lb.
* HIV
* hypothyroid
* steroid medication, fenofibrate
* smoking
* BP \> 140/90
* heart disease
* pregnant or lactating
* consumption of \> 5 alcoholic drinks/wk
* creatinine \> 1.5 mg/dL
* hematocrit \< 28

Primary outcomes:
measure: Change in Cardiac Diastolic Function as Measured by E' (cm/s)
timeFrame: Baseline and 12 weeks
measure: Change in Cardiac Systolic Function as Measured by Fractional Shortening Percent
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change in C24:0/C16:0 Ceramide Ratio
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Jean E Schaffer, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Hamby RI, Zoneraich S, Sherman L. Diabetic cardiomyopathy. JAMA. 1974 Sep 23;229(13):1749-54. No abstract available.
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citation: 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.
citation: 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.
citation: 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