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Targeting Sympathetic Overactivity in Heart Failure Patients With Statins

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ClinicalTrials.gov Identifier: NCT01097785
Recruitment Status : Completed
First Posted : April 2, 2010
Results First Posted : November 21, 2016
Last Update Posted : November 21, 2016
Sponsor:
Collaborator:
University of Nebraska
Information provided by (Responsible Party):
University of Missouri-Columbia

Brief Summary:
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 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 or disease Intervention/treatment Phase
Heart Failure Drug: Simvastatin Drug: Placebo Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Targeting Sympathetic Overactivity in Heart Failure Patients With Statins
Study Start Date : March 2009
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Simvastatin
40 mg Simvastatin 1 pill every day for 30 days
Drug: Simvastatin
40 mg, P.O.,daily for 30 days
Other Name: Zocor
Placebo Comparator: Placebo
Placebo cap 1 pill every day for 30 days
Drug: Placebo
1 capsule daily for 30 days



Primary Outcome Measures :
  1. Change in Muscle Sympathetic Nerve Activity in Bursts Per 100 Heartbeats [ Time Frame: Baseline and 30 days ]
    Muscle sympathetic nerve activity will be assessed after one month of placebo and statin therapy; measured in bursts/100 heartbeats.


Secondary Outcome Measures :
  1. Change in Measures of Reactive Oxygen Species in the Blood [ Time Frame: Baseline and 30 days ]
    Reactive Oxygen Species will be assessed after one month of placebo and statin therapy; measured using electron parametric resonance spectroscopy (EPR).



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
  • Chronic Obstructive Pulmonary Disease (COPD) with concurrent daily use of inhalers
  • Peripheral neuropathy
  • Pregnant women

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 ClinicalTrials.gov identifier (NCT number): NCT01097785


Locations
United States, Missouri
University of Missouri
Columbia, Missouri, United States, 65212
Sponsors and Collaborators
University of Missouri-Columbia
University of Nebraska
Investigators
Principal Investigator: Paul J Fadel, PhD University of Missouri-Columbia
Study Chair: Anand Chockalingam, M.D. University of Missouri-Columbia

Responsible Party: University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT01097785     History of Changes
Other Study ID Numbers: IRB-1135098
First Posted: April 2, 2010    Key Record Dates
Results First Posted: November 21, 2016
Last Update Posted: November 21, 2016
Last Verified: September 2016

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