Clinical trial NCT00600392: DNA/RNA Analysis of Blood and Skeletal Muscle in Patients Undergoing Cardiac Resynchronization Therapy (CRT)
Official title: Transcriptomal Analysis of Peripheral Blood and Skeletal Muscle in Patients Undergoing CRT Using Oligonucleotide Arrays
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiomyopathy (Ischemic or Non-Ischemic)
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2008-01-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who are scheduled for a CRT-D device

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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).
timeFrame: 6 months
Secondary outcomes:
measure: Improved LV synchrony as determined by TDI, Decrease in blood markers of inflammation and Oxidative stress and catabolism.
timeFrame: 6 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Patrick Hranitzky, MD
role: PRINCIPAL_INVESTIGATOR
References: