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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00600392
Recruitment Status : Completed
First Posted : January 25, 2008
Last Update Posted : January 20, 2016
Information provided by (Responsible Party):
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

Condition or disease
Cardiomyopathy (Ischemic or Non-Ischemic)

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 Type : Observational
Actual Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Transcriptomal Analysis of Peripheral Blood and Skeletal Muscle in Patients Undergoing CRT Using Oligonucleotide Arrays
Study Start Date : January 2006
Actual Primary Completion Date : October 2008
Actual Study Completion Date : December 2011

patients who meet criteria for CRT-D implantation

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Improved LV synchrony as determined by TDI, Decrease in blood markers of inflammation and Oxidative stress and catabolism. [ Time Frame: 6 months ]

Biospecimen Retention:   Samples With DNA

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

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients who are scheduled for a CRT-D device

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00600392

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Principal Investigator: Patrick Hranitzky, MD Duke University

Responsible Party: Duke University Identifier: NCT00600392     History of Changes
Other Study ID Numbers: Pro00009277
7523 ( Other Identifier: Duke legacy protocol number )
First Posted: January 25, 2008    Key Record Dates
Last Update Posted: January 20, 2016
Last Verified: November 2012

Additional relevant MeSH terms:
Heart Diseases
Cardiovascular Diseases