Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Targeting Sympathetic Overactivity in Heart Failure Patients With Statins

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University of Missouri-Columbia
Sponsor:
Collaborator:
University of Nebraska
Information provided by (Responsible Party):
Paul Fadel, PhD, University of Missouri-Columbia
ClinicalTrials.gov Identifier:
NCT01097785
First received: March 26, 2010
Last updated: June 25, 2013
Last verified: June 2013
  Purpose

Heart failure (HF) is a leading cause of morbidity and mortality in the United States with the incidence and prevalence of the disease on a continual rise. An overactive sympathetic nervous system has become a hallmark characteristic of HF. Although sympathetic activation is initially beneficial to maintain cardiac output, blood pressure and perfusion to vital organs, over the long term it becomes deleterious contributing to the worsening of HF and sudden cardiac death. Indeed, recent findings in HF patients suggest that the sympathetic overactivity is not just a marker of poor prognosis but it plays a causative role in the development of the disease. Thus, the sympathetic nervous system constitutes a putative drug target in the treatment of HF. However, despite aggressive medical management, including conventional anti-adrenergic strategies, sympathetic nerve activity (SNA) has been shown to remain abnormally high in HF patients and improvements in survival have been limited. Thus, other treatment strategies that include reducing SNA and its deleterious consequences are warranted. Recent findings from clinical trials indicate that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improve survival irrespective of cholesterol lowering bringing the pleiotropic (i.e., cholesterol independent) effects of statins to the forefront. An important pleiotropic effect recently reported in experimental HF, that has yet to be directly tested in human HF, is the ability of statins to reduce resting sympathetic outflow. Several studies in pacing-induced HF rabbits have demonstrated that statins normalize the excessive sympathetic activation in the HF state. Thus, the goal of this project is to determine whether these findings in experimental HF can be translated to the clinical setting of human HF. Our central hypothesis is that statins reduce sympathetic overactivity in HF patients. To test this hypothesis we will directly measure muscle SNA and perform a randomized crossover placebo control study. Subjects will come to the research laboratory before and after the administration of Simvastatin at a standard therapeutic dosage of 40 mg. per day or placebo for 1 month


Condition Intervention
Heart Failure
Drug: Simvastatin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Targeting Sympathetic Overactivity in Heart Failure Patients With Statins

Resource links provided by NLM:


Further study details as provided by University of Missouri-Columbia:

Primary Outcome Measures:
  • Changes in muscle sympathetic nerve activity pre and post-statin therapy [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Muscle sympathetic nerve activity will be assessed before and after one month of placebo and statin therapy


Secondary Outcome Measures:
  • Measures of reactive oxygen species in the blood [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Reactive Oxygen Species will be assessed before and after one month of placebo and statin therapy


Estimated Enrollment: 30
Study Start Date: March 2009
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Simvastatin
40 mg Simvastatin
Drug: Simvastatin
40 mg, P.O.,daily for 30 days
Other Name: Zocor
Placebo Comparator: Placebo Drug: Placebo
1 capsule daily for 30 days
Other Name: placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male and females of all ethnic backgrounds ranging aged 18 to 70
  • Ages 18-70 yrs
  • Patients with congestive heart failure diagnosed on clinical history, a routine exercise test, echocardiography and/or routine cardiac catheterization, in functional class I-III
  • Patients with heart failure due to ischemic and non-ischemic etiologies
  • Normotensive and not taking blood pressure controlling medications

Exclusion Criteria:

  • Low blood pressure (<100/60)
  • End stage renal disease
  • COPD with concurrent daily use of inhalers
  • Peripheral neuropathy
  • Pregnant women
  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: NCT01097785

Contacts
Contact: Paul J Fadel, Ph.D. 573-884-5220 fadelp@health.missouri.edu

Locations
United States, Missouri
University of Missouri Recruiting
Columbia, Missouri, United States, 65212
Contact: Paul J Fadel, Ph.D.    573-884-5220    fadelp@health.missouri.edu   
Principal Investigator: Paul J Fadel, Ph.D.         
Sponsors and Collaborators
Paul Fadel, PhD
University of Nebraska
Investigators
Principal Investigator: Paul J Fadel, PhD University of Missouri-Columbia
Study Chair: Anand Chockalingam, M.D. University of Missouri-Columbia
  More Information

No publications provided

Responsible Party: Paul Fadel, PhD, Paul J Fadel, Ph.D, University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT01097785     History of Changes
Other Study ID Numbers: IRB-1135098
Study First Received: March 26, 2010
Last Updated: June 25, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Simvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014