Augmentation of Parasympathetic Signaling With Pyridostigmine in Heart Failure
Overview
- Phase
- Phase 2
- Intervention
- Pyridostigmine Bromide
- Conditions
- Heart Failure
- Sponsor
- NYU Langone Health
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Baseline Heart Rate Recovery
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
Heart failure, a common heart disease affecting nearly 6 million Americans, is associated with high rates of hospitalization and death. Abnormalities in the autonomic nervous system are thought to play an important role in the progression of heart failure. This proposal aims to determine whether novel application of pyridostigmine, a drug currently approved by the FDA only for the treatment of neuromuscular disease, can improve autonomic nervous system function in heart failure patients.
Detailed Description
Autonomic dysregulation of the cardiovascular system, characterized by heightened sympathetic activity and withdrawal of parasympathetic activity promotes progression of heart failure. Pharmacological blockade of sympathetic overactivity is associated with reduced mortality risk, but there are few data on pharmacologic augmentation of parasympathetic withdrawal. Acetylcholinesterase inhibitors augment parasympathetic neurotransmission by blocking the enzymatic breakdown of acetylcholine at cholinergic receptor sites. Pyridostigmine is a short-acting, reversible acetylcholinesterase inhibitor approved by the FDA for the treatment of myasthenia gravis. Investigators propose a Phase II prospective randomized, double-blind trial to compare 12 weeks of treatment with ascending doses of pyridostigmine (15, 30, and 60 mg every 8 hours) vs. matching placebo in 60 patients with symptomatic chronic heart failure associated with left ventricular systolic dysfunction.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 21-75 years
- •Symptomatic NYHA Class II-III heart failure \>6 months
- •Left ventricular ejection fraction \<35%
- •Previous implantation of implantable cardiovertor defibrillator or pacemaker
- •Guideline-recommended heart failure treatment for \> 3 months
- •Able and willing to provide written informed consent
Exclusion Criteria
- •Contraindications to cholinergic stimulation
- •Heart failure primarily attributable to genetic, valvular, infiltrative diseases
- •Persistent atrial fibrillation
- •Sick sinus syndrome
- •Pacemaker dependency during exercise
- •Severe chronotropic incompetence with peak exercise heart rate \< 100 min-1
- •Severe exercise intolerance (unable to complete first stage of Bruce Protocol)
- •Coronary or cerebral atherothrombotic events within the past year
- •Hospitalization of emergency room visit for heart failure within last 3 months
- •ICD shock in last 6 months
Arms & Interventions
Pyridostigmine Bromide
Forced titration protocol 15-60 mg every 8 hours as tolerated
Intervention: Pyridostigmine Bromide
Placebo
Matching placebo forced titration 15-60 mg as tolerated
Intervention: Pyridostigmine Bromide
Outcomes
Primary Outcomes
Baseline Heart Rate Recovery
Time Frame: Baseline
Change in peak HR at end of exercise to 1 minute post-exercise (beats per minute)
Post Exercise Heart Rate Recovery
Time Frame: 12 weeks
Change in heart rate from peak exercise to 1 minute post-exercise (beats per minute)