Heart FailurePhase 2APP-HFNCT01415921
Safety Study of Pyridostigmine in Heart Failure
A Phase 2 study testing Pyridostigmine Bromide in people with Heart Failure, run by NYU Langone Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Pyridostigmine Bromide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Jul 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 25Show fewer
- 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
- Serum creatinine >2.5 mg/dl
- Liver function tests >3 times upper limit of normal
- Severe anemia (Hemoglobin <10 gm/dl)
- FEV1.0 < 60% of predicted or FEV1.0/FVC ratio <70%
- PR interval >240 msec or second or third degree heart block on electrocardiogram
- Exercise limited primarily by angina or non-cardiac co-morbid condition
- Pregnant or breast-feeding women
- Current treatment with medications known to interact with pyridostigmine
- Known intolerance of oral preparations containing bromides
- Any condition (e.g., psychiatric illness or active substance abuse) or situation that, in the investigator's opinion, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's ability to adhere with study procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University Langone Medical Center
New York, New York, 10016
About this study
Official title: Augmentation of Parasympathetic Signaling With Pyridostigmine in Heart Failure
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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- Pyridostigmine Bromide
- Keywords
- heart failure, autonomic function, sympathovagal balance, cholinesterase inhibitors, pharmacology
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyridostigmine BromideDrug
Also called Mestinon
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.
| Study group | Role | What they receive |
|---|---|---|
| Pyridostigmine Bromide | Experimental | Forced titration protocol 15-60 mg every 8 hours as tolerated Receives: Drug: Pyridostigmine Bromide |
| Placebo | Placebo comparator | Matching placebo forced titration 15-60 mg as tolerated Receives: Drug: Pyridostigmine Bromide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline Heart Rate Recovery
Change in peak HR at end of exercise to 1 minute post-exercise (beats per minute)
Measured: Baseline
Post Exercise Heart Rate Recovery
Change in heart rate from peak exercise to 1 minute post-exercise (beats per minute)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2011 (estimated)
- Study startOct 2011
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Nathan Kline Institute for Psychiatric Research, Oklahoma State University, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Stuart D Katz, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01415921
- Sponsor's protocol ID
- 10-02167
- Other IDs
- 10-02167, 1R01HL103988
- Acronym
- APP-HF
- Status last verified
- Jul 2017
- First submitted
- 10 Aug 2011
- Last updated
- 31 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 12860856Goldberg 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.
PubMed 41357360
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Augmentation of Parasympathetic Signaling With Pyridostigmine in Heart Failure
- ClinicalTrials.gov ID
- NCT01415921
- Acronym / sponsor ID
- APP-HF / 10-02167
- Conditions
- Heart Failure
- Keywords
- heart failure, autonomic function, sympathovagal balance, cholinesterase inhibitors, pharmacology
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- Nathan Kline Institute for Psychiatric Research, Oklahoma State University, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Oct 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 12 Aug 2011 (estimated)
- Results
- Posted 25 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyridostigmine Bromide | Experimental | Drug: Pyridostigmine BromideForced titration protocol 15-60 mg every 8 hours as tolerated |
| Placebo | Placebo comparator | Drug: Pyridostigmine BromideMatching placebo forced titration 15-60 mg as tolerated |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (25 listed)
- Contraindications to cholinergic stimulation
- Heart failure primarily attributable to genetic, valvular, infiltrative diseases
- Persistent atrial fibrillation
- Sick sinus syndrome
- Pacemaker dependency during exercise
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyridostigmine BromideAlso: Mestinon15, 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. | Drug | Placebo, Pyridostigmine Bromide |
Primary outcome
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12860856Androne 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.
- Derived from this study: PubMed 41357360Goldberg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart D Katz, MD principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pyridostigmine Bromide in people with Heart Failure, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline Heart Rate Recovery (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01415921, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2017.