Lipid Biomarkers for Diabetic Heart Disease

Diabetes Complications Clinical Trial

Official title:

Lipid Biomarkers for Diabetic Heart Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01752842
• Other study ID #: 201112122
• Secondary ID: P20HL113444-01
• Status: Completed
• Phase: N/A
• Start date: March 2013
• Est. completion date: February 23, 2018

Study information

• Verified date: February 2019
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 23, 2018
• Est. primary completion date: February 23, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Complications
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Heart Diseases
• Type II Diabetes Mellitus

Intervention

Drug:
• Fenofibrate

• Placebo for fenofibrate

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (4)

Lead Sponsor	Collaborator
Washington University School of Medicine	Leducq Foundation, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (7)

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

Hamby RI, Zoneraich S, Sherman L. Diabetic cardiomyopathy. JAMA. 1974 Sep 23;229(13):1749-54. — View Citation

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. Epub 2006 Jan 18. — View Citation

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. — View Citation

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. Epub 2004 May 3. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline and 12 weeks
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.	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.	Baseline and 12 weeks