Targeting Sympathetic Overactivity in Heart Failure Patients With Statins

NCT01097785 | Completed Results DMC

• 1 other identifier: IRB-1135098
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Change in Muscle Sympathetic Nerve Activity in Bursts Per 100 Heartbeats

  Muscle sympathetic nerve activity will be assessed after one month of placebo and statin therapy; measured in bursts/100 heartbeats.

  Baseline and 30 days

Secondary Outcomes (1)

• Change in Measures of Reactive Oxygen Species in the Blood

  Baseline and 30 days

Study Arms (2)

Simvastatin

ACTIVE COMPARATOR

40 mg Simvastatin 1 pill every day for 30 days

Drug: Simvastatin

Placebo

PLACEBO COMPARATOR

Placebo cap 1 pill every day for 30 days

Drug: Placebo

Interventions

Simvastatin DRUG

40 mg, P.O.,daily for 30 days

Also known as: Zocor

Simvastatin

Placebo DRUG

1 capsule daily for 30 days

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Low blood pressure (\<100/60)
• End stage renal disease
• Chronic Obstructive Pulmonary Disease (COPD) with concurrent daily use of inhalers
• Peripheral neuropathy
• Pregnant women

Sponsors & Collaborators

• University of Missouri-Columbia: lead
• University of Nebraska: collaborator

Study Sites (1)

University of Missouri

Columbia, Missouri, 65212, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Paul Fadel
• Organization: University of Missouri

fadelp@health.missouri.edu

1-573-884-5220

Study Officials

• Paul J Fadel, PhD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

• Anand Chockalingam, M.D.

  University of Missouri-Columbia

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2010
• First Posted: April 2, 2010
• Study Start: March 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: November 21, 2016
• Results First Posted: November 21, 2016

Record last verified: 2016-09

Locations

US (1)