Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 10-02167 | Other Identifier | NYU IRB | |
| 1R01HL103988 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Nathan Kline Institute for Psychiatric Research | OTHER |
| Oklahoma State University | OTHER |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pyridostigmine Bromide | Experimental | Forced titration protocol 15-60 mg every 8 hours as tolerated |
|
| Placebo | Placebo Comparator | Matching placebo forced titration 15-60 mg as tolerated |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pyridostigmine Bromide | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Stuart D Katz, MD | NYU Langone Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New York University Langone Medical Center | New York | New York | 10016 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12860856 | Background | 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. | |
| 41357360 | Derived | Goldberg 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. |
Not provided
Not provided
Not provided
Admissions logs and other existing electronic hospital information systems
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Pyridostigmine Bromide | Forced titration protocol 15-60 mg every 8 hours as tolerated Pyridostigmine Bromide: 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. |
| FG001 | Placebo | Matching placebo forced titration 15-60 mg as tolerated Pyridostigmine Bromide: 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Pyridostigmine Bromide | Forced titration protocol 15-60 mg every 8 hours as tolerated Pyridostigmine Bromide: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Baseline Heart Rate Recovery | Change in peak HR at end of exercise to 1 minute post-exercise (beats per minute) | Heart rate recovery is also measured as beats/min (peak HR at end of exercise - HR 1 min post exercise = HRR). | Posted | Mean | Standard Deviation | beats per minute | Baseline |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pyridostigmine Bromide | Forced titration protocol 15-60 mg every 8 hours as tolerated Pyridostigmine Bromide: 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Decompensated Heart Failure | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stuart Katz, MD | New York University School of Medicine | 212-263-3946 | stuart.katz@nyumc.org |
Not provided
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D011729 | Pyridostigmine Bromide |
| ID | Term |
|---|---|
| D011726 | Pyridinium Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Withdrawal by Subject |
|
| Other |
|
| BG001 | Placebo | Matching placebo forced titration 15-60 mg as tolerated Pyridostigmine Bromide: 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Matching placebo forced titration 15-60 mg as tolerated Pyridostigmine Bromide: 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. |
|
|
| Primary | Post Exercise Heart Rate Recovery | Change in heart rate from peak exercise to 1 minute post-exercise (beats per minute) | Heart rate recovery is also measured as beats/min (peak HR at end of exercise - HR 1 min post exercise = HRR). | Posted | Mean | Standard Deviation | beats per minute | 12 weeks |
|
|
|
| 2 |
| 16 |
| 11 |
| 16 |
| EG001 | Placebo | Matching placebo forced titration 15-60 mg as tolerated Pyridostigmine Bromide: 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. | 3 | 17 | 10 | 17 |
| Elective Stent Placement | Cardiac disorders | Systematic Assessment |
|
| Abdominal Paim | Gastrointestinal disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Ventricular Malposition of an ICD Lead | Cardiac disorders | Systematic Assessment |
|
| Chest Pain | Cardiac disorders |
|
| Blurred vision of right eye | Eye disorders |
|
| Loose Stools | Gastrointestinal disorders |
|
| Flatulence | Gastrointestinal disorders |
|
| Diarrhea | Gastrointestinal disorders |
|
| Bloating | Gastrointestinal disorders |
|
| Abdominal Pain | Gastrointestinal disorders |
|
| Black Stool | Gastrointestinal disorders |
|
| Vomiting | Gastrointestinal disorders |
|
| Flu like symptoms | General disorders |
|
| Fatigue | General disorders |
|
| Upper respiratory tract infection | Infections and infestations |
|
| Cellulitis | Infections and infestations |
|
| Ankle sprain | Injury, poisoning and procedural complications |
|
| Pacemaker AMS | Investigations |
|
| Inadequate ICD shock | Investigations |
|
| Ventricular pacing | Investigations |
|
| Supraventicular tachycardia reported on ICD | Investigations |
|
| Total Bilirubin Increased | Investigations |
|
| Elevated Alkaline Phosphatase | Investigations |
|
| Elevated hepatic enzymes | Investigations |
|
| Thrombocitopenia | Investigations |
|
| Percent Eosinophils Increased | Investigations |
|
| PMT (Pacemaker Tachycardia) | Investigations |
|
| Pain in lower extremities | Musculoskeletal and connective tissue disorders |
|
| Tendinitis | Musculoskeletal and connective tissue disorders |
|
| Plantar Fasciitis | Musculoskeletal and connective tissue disorders | Plantar Fasciitis |
|
| Gout | Musculoskeletal and connective tissue disorders |
|
| Dizziness | Nervous system disorders | Dizziness |
|
| Urinary Incontinence | Renal and urinary disorders | Urinary Incontinence |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | Sore throat |
|
| Sweating | Skin and subcutaneous tissue disorders | Sweating |
|
| Rash | Skin and subcutaneous tissue disorders | Rash |
|
| Low heart rate | Vascular disorders | Low heart rate |
|
| Hypertension | Vascular disorders | Hypertension |
|
Not provided
Not provided
Not provided