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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00600392
First received: January 15, 2008
Last updated: July 11, 2014
Last verified: November 2012
  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)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Transcriptomal Analysis of Peripheral Blood and Skeletal Muscle in Patients Undergoing CRT Using Oligonucleotide Arrays

Resource links provided by NLM:


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

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


Enrollment: 30
Study Start Date: January 2006
Study Completion Date: December 2011
Primary Completion Date: October 2008 (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:

  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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00600392     History of Changes
Other Study ID Numbers: Pro00009277, 7523
Study First Received: January 15, 2008
Last Updated: July 11, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 01, 2014