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

Purpose

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

Condition

Cardiomyopathy (Ischemic or Non-Ischemic)

MedlinePlus related topics:

Cardiomyopathy Exercise and Physical Fitness

U.S. FDA Resources

Study Type:	Observational
Study Design:	Cohort, Prospective

Official Title:	Transcriptomal Analysis of Peripheral Blood and Skeletal Muscle in Patients Undergoing CRT Using Oligonucleotide Arrays

Further study details as provided by Duke University:

Primary Outcome Measures:

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). [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Improved LV synchrony as determined by TDI, Decrease in blood markers of inflammation and Oxidative stress and catabolism. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Serum TNF alpha, IL-1, IL6, CRP, uric acid, albumin, BNP, IGF-1 and growth hormone at baseline and at 6 months.

50 ml of blood will be collected at baseline and at 6 months. It will be divided into aliquots as follows; 10 ml in Pax-gene tubes for mRNA extraction, 20 ml for various other biomarkers, 10 ml for proteomics and 10 ml will be stored for any future use.

Approximately a 5x5 - 7x7mm muscle biopsy will be obtained from the mid thigh region of each subject at baseline and at six months

Estimated Enrollment:	40
Study Start Date:	January 2006
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Groups/Cohorts

1

patients who meet criteria for CRT-D implantation

Detailed Description:

1. The general objective of this study is to:

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
To identify objective measurable molecular signals, using gene expression profiling, that correlate with clinical improvement in patients undergoing CRT.
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.
To identify biochemical pathways involved in cardiac cachexia.
To identify genes involved in positive remodeling and reversal of apoptotic cascade in the skeletal muscle.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Patients who are scheduled for a CRT-D device

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00600392

Contacts


Contact: Margaret Stewart, RN	919-668-3524	stewa070@mc.duke.edu

Locations


United States, North Carolina
	Duke University Medical Center	Recruiting
	Durham, North Carolina, United States, 27710
	Contact: Margaret Stewart, RN 919-668-3524 stewa070@mc.duke.edu
	Principal Investigator: Patrick Hranitzky, MD

Sponsors and Collaborators

Duke University

Investigators


Principal Investigator:	Patrick Hranitzky, MD	Duke University

More Information

Responsible Party:	Duke University Medical Center ( Patrick Hranitzky, MD )
Study ID Numbers:	00009277 / 7523, Not applicable to our study
First Received:	January 15, 2008
Last Updated:	August 15, 2008
ClinicalTrials.gov Identifier:	NCT00600392
Health Authority:	United States: Institutional Review Board

Study placed in the following topic categories:

Heart Diseases

Ischemia

Cardiomyopathies

Additional relevant MeSH terms:

Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 28, 2008

Sponsored by:	Duke University
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00600392