Augmentation of Parasympathetic Signaling With Pyridostigmine in Heart Failure
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Baseline Heart Rate Recovery
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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.
研究组 & 干预措施
Pyridostigmine Bromide
Forced titration protocol 15-60 mg every 8 hours as tolerated
干预措施: Pyridostigmine Bromide (Drug)
Placebo
Matching placebo forced titration 15-60 mg as tolerated
干预措施: Pyridostigmine Bromide (Drug)
结局指标
主要结局
Baseline Heart Rate Recovery
时间窗: Baseline
Change in peak HR at end of exercise to 1 minute post-exercise (beats per minute)
Post Exercise Heart Rate Recovery
时间窗: 12 weeks
Change in heart rate from peak exercise to 1 minute post-exercise (beats per minute)
次要结局
未报告次要终点