DNA/RNA Analysis of Blood and Skeletal Muscle in Patients Undergoing Cardiac Resynchronization Therapy (CRT)

Completed

• Conditions: Cardiomyopathy (Ischemic or Non-Ischemic)

• Registration Number: NCT00600392
• Lead Sponsor: Duke University

Brief Summary

Genes expressing inflammatory cytokines (TNF- alpha, IL1 etc) and genes involved in apoptosis (Caspase 3, Bax, Bcl-2, Fas) are dysregulated in the skeletal muscles of the patients who have muscle wasting and decreased exercise capacity with CHF.

Patients who show benefit from CRT may also show reversal of the inflammatory/apoptotic cascade that accompanies CHF and these patients may be the ones who benefit the most from CRT

Detailed Description

1. The general objective of this study is to:

1. To identify the molecular pathways that may be altered in the blood and skeletal muscles of the patients undergoing CRT by using transcriptional analysis of the blood and skeletal muscle in these patients

2. To identify objective measurable molecular signals, using gene expression profiling, that correlate with clinical improvement in patients undergoing CRT.

3. To identify the molecular profile of patients who are most likely to benefit from CRT with improvement of exercise capacity and reversal of cardiac cachexia.

4. To identify biochemical pathways involved in cardiac cachexia.

5. To identify genes involved in positive remodeling and reversal of apoptotic cascade in the skeletal muscle.

Study Timeline

• Study Start: 2006-01
• Study First Submitted: 2008-01-15
• Study First Submitted QC: 2008-01-24
• Study First Posted: 2008-01-25
• Primary Completion: 2008-10
• Study Completion: 2011-12
• Status Verified: 2012-11
• Last Update Submitted: 2016-01-15
• Last Update Posted: 2016-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Patients with poor LV function and an EF of ≤35%
• Patients who are symptomatic with Class II or Class III heart failure on optimal medical therapy.
• Patients with EKG showing QRS duration of greater than 120 ms and meet criteria for Bi-ventricular ICD implantation.

Exclusion Criteria

• Patients with other co-morbid conditions which could contribute to cachexia, such as end stage renal disease, ongoing malignancy, chronic or acute liver failure, age greater than 80yrs.
• Patients who are unable to walk and are wheelchair bound or need assistance to walk for reasons other than CHF.
• Patients with muscular dystrophies and myopathies.
• Patients with untreated hyper or hypothyroidism.
• Patients on Dialysis.
• Patients with recent (<12 weeks) revascularization.
• Patients with recent (<12 weeks) myocardial infarction.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Shift of the muscle transcriptome away from Apoptosis/Inflammation. Reversal of active apoptosis in skeletal muscle.Quality of life assessment(Minn.HF Ques) Exercise capacity (6 min walk).	6 months

Secondary Outcome Measures

Name	Time	Method
Improved LV synchrony as determined by TDI, Decrease in blood markers of inflammation and Oxidative stress and catabolism.	6 months

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States