Safety Study of Pyridostigmine in Heart Failure
APP-HF
Augmentation of Parasympathetic Signaling With Pyridostigmine in Heart Failure
2 other identifiers
interventional
33
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 heart-failure
Started Oct 2011
Typical duration for phase_2 heart-failure
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 10, 2011
CompletedFirst Posted
Study publicly available on registry
August 12, 2011
CompletedStudy Start
First participant enrolled
October 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedResults Posted
Study results publicly available
October 25, 2016
CompletedJuly 31, 2017
July 1, 2017
3.8 years
August 10, 2011
May 20, 2016
July 27, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Baseline Heart Rate Recovery
Change in peak HR at end of exercise to 1 minute post-exercise (beats per minute)
Baseline
Post Exercise Heart Rate Recovery
Change in heart rate from peak exercise to 1 minute post-exercise (beats per minute)
12 weeks
Study Arms (2)
Pyridostigmine Bromide
EXPERIMENTALForced titration protocol 15-60 mg every 8 hours as tolerated
Placebo
PLACEBO COMPARATORMatching placebo forced titration 15-60 mg as tolerated
Interventions
15, 30, and 60 mg tabs, 1 tab every 8 hours for 10 weeks. Forced titration protocol increases dose at 2 week intervals from 15 to 30 to 60 mg as tolerated. Continue maximally tolerated dose for 4 weeks and then downtitrate at weekly intervals (60 to 30 to 15) and then discontinue.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- Diabetes mellitus with peripheral neuropathy
- Autonomic or peripheral neuropathy of any cause
- Systolic blood pressure \<90 or \>160 mmHg
- Resting heart rate \<60 or \>100 min-1
- Serum sodium \< 132 mmol/L
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NYU Langone Healthlead
- Nathan Kline Institute for Psychiatric Researchcollaborator
- Oklahoma State Universitycollaborator
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
Study Sites (1)
New York University Langone Medical Center
New York, New York, 10016, United States
Related Publications (2)
Androne AS, Hryniewicz K, Goldsmith R, Arwady A, Katz SD. Acetylcholinesterase inhibition with pyridostigmine improves heart rate recovery after maximal exercise in patients with chronic heart failure. Heart. 2003 Aug;89(8):854-8. doi: 10.1136/heart.89.8.854.
PMID: 12860856BACKGROUNDGoldberg R, Norcliffe-Kaufmann L, Kaufmann H, Jeschke-Lopez I, Guo Y, Zhong J, Berger KI, Goldring RM, Goldstein DS, Pope C, Maxwell L, Bharadwaj M, Reyentovich A, Katz SD. Pharmacodynamics, Safety, and Tolerability of Pyridostigmine Bromide in Heart Failure. Curr Ther Res Clin Exp. 2025 Oct 31;103:100814. doi: 10.1016/j.curtheres.2025.100814. eCollection 2025.
PMID: 41357360DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Stuart Katz, MD
- Organization
- New York University School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Stuart D Katz, MD
NYU Langone Health
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 10, 2011
First Posted
August 12, 2011
Study Start
October 1, 2011
Primary Completion
July 1, 2015
Study Completion
July 1, 2015
Last Updated
July 31, 2017
Results First Posted
October 25, 2016
Record last verified: 2017-07