Lipid Biomarkers for Diabetic Heart Disease

Not Applicable

Completed

Conditions: Type II Diabetes Mellitus
Diabetes Complications

Interventions: Drug: Placebo for fenofibrate
Drug: Fenofibrate

Registration Number: NCT01752842

Lead Sponsor: Washington University School of Medicine

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 70

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo for fenofibrate	Placebo for fenofibrate	One inert sugar pill per day for 12 weeks
Fenofibrate	Fenofibrate	One fenofibrate 160 mg capsule per day for 12 weeks

Primary Outcome Measures

Name	Time	Method
Change in Cardiac Diastolic Function as Measured by E' (cm/s)	Baseline and 12 weeks	Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline.
Change in Cardiac Systolic Function as Measured by Fractional Shortening Percent	Baseline and 12 weeks	Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline.

Secondary Outcome Measures

Name	Time	Method
Change in C24:0/C16:0 Ceramide Ratio	Baseline and 12 weeks	Mass spectrometry-based quantification of the ratio of C24:0 ceramide to C16:0 ceramide in plasma.