Dichlorphenamide vs. Placebo for Periodic Paralysis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 71
- 试验地点
- 12
- 主要终点
- HYP Attack Rate
研究概览
简要总结
The purpose of this study is to compare Dichlorphenamide with placebo (an inactive substance) for prevention of episodes and for improvement of strength in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. This study will also look at the long-term effects of Dichlorphenamide in periodic paralysis.
详细描述
Periodic paralysis is a relatively rare, life-long disorder characterized by intermittent bouts of paralysis, progressive weakness, and diminished quality of life. Two drugs, acetazolamide (ACZ) and dichlorphenamide, have been prescribed to treat the disorder, however, dichlorphenamide is no longer available.
In this multi-center, parallel, randomized trial researchers will compare the effects of dichlorphenamide vs. placebo in patients with hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis.
The trial consists of two 9-week studies-one study will enroll persons with hyperkalemic periodic paralysis and the other study will enroll persons with hypokalemic periodic paralysis. Participants will be randomly assigned to one of two treatment groups: dichlorphenamide or placebo (an inactive substance). During the studies, participants will be asked to keep a daily diary to record the time, length, and severity of each episode of weakness (attack). The study coordinator will contact participants weekly to review the diary information.
The 9-week phase will be followed by a 1-year open-label dichlorphenamide extension without placebo to determine the long-term effects of dichlorphenamide on the course of the disease and on inter-attack weakness.
Duration of the trial for participants is approximately 65 weeks, including a screening phase to determine eligibility, the first 9-week treatment phase, and the one-year open-label extension phase.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetically definite, clinically definite or clinically probable Hyperkalemic or Hypokalemic Periodic Paralysis as outlined in the protocol
- •Male and female participants, age 18 and older who are able to comply with the study conditions.
- •Participants who have distinct regular episodes of weakness with an average frequency of > or = to 1 a week and < or = to 3 a day either on or off treatment, whichever is higher
- •Normal thyroid-stimulating hormone (TSH) level
排除标准
- •Evidence for Andersen-Tawil syndrome (any one of the following 3 criteria)
- •Prolonged QT interval or complex ventricular ectopy between attacks
- •Distinctive physical features (2 of the following 5)
- •Low set ears
- •Short stature
- •Hypo-/micrognathia
- •Clinodactyly
- •Hypo-/hypertelorism
- •KIR 2.1 gene mutation
- •Coincidental renal, hepatic, active thyroid disease, restrictive or obstructive lung disease, other neuromuscular disease, or heart disease
- •Chronic, non-congestive, angle-closure glaucoma
- •Use of any of the following medications for reasons other than treatment of periodic paralysis: diuretics, antiarrhythmics, corticosteroids, beta-blockers, calcium channel blockers, antiepileptics, magnesium
- •History of life-threatening episodes of respiratory muscle weakness or cardiac arrhythmias during attacks
- •Pregnancy
- •Known mutation in the alpha subunit of the sodium channel gene in hypokalemic periodic paralysis patients
研究组 & 干预措施
HYP Dichlorphenamide
Hyperkalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
干预措施: Dichlorphenamide (double-blind) (Drug)
HYP Dichlorphenamide
Hyperkalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
干预措施: Dichlorphenamide (open-label) (Drug)
HYP Placebo
Hyperkalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
干预措施: Placebo (double-blind) (Drug)
HYP Placebo
Hyperkalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
干预措施: Dichlorphenamide (open-label) (Drug)
HOP Dichlorphenamide
Hypokalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
干预措施: Dichlorphenamide (double-blind) (Drug)
HOP Dichlorphenamide
Hypokalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
干预措施: Dichlorphenamide (open-label) (Drug)
HOP Placebo
Hypokalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
干预措施: Placebo (double-blind) (Drug)
HOP Placebo
Hypokalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase.
干预措施: Dichlorphenamide (open-label) (Drug)
结局指标
主要结局
HYP Attack Rate
时间窗: 8 weeks
The number of distinct attacks per week over the final 8 weeks (Weeks 2-9) of the double-blind treatment period as self-reported by HYP participants.
HOP Attack Rate
时间窗: 8 weeks
The number of distinct attacks per week over the final 8 weeks (Weeks 2-9) of the double-blind treatment period as self-reported by HOP participants.
次要结局
- HOP Change From Baseline to Week 9 in Average Manual Muscle Testing (MMT) Score(Baseline and 9 weeks)
- HYP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing (MVICT) Scores(Baseline and 9 weeks)
- HYP Attack Duration(8 weeks)
- HYP Change From Baseline to Week 9 in Lean Body Mass(Baseline and 9 weeks)
- HOP Change From Baseline to Week 9 in Lean Body Mass(Baseline and 9 weeks)
- HOP Attack Duration(8 weeks)
- HYP Severity-weighted Attack Rate(8 weeks)
- HYP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing Percent of Predicted Normal(Baseline and 9 weeks)
- HYP Change From Baseline to Week 9 in SF-36 Physical Component Summary Score(Baseline and 9 weeks)
- HOP Change From Baseline to Week 9 in SF-36 Physical Component Summary Score(Baseline and 9 weeks)
- HOP Change From Baseline to Week 9 in SF-36 Mental Health Component Summary Score(Baseline and 9 weeks)
- HOP Severity-weighted Attack Rate(8 weeks)
- HYP Endpoint of Acute Worsening(0-9 weeks)
- HOP Endpoint of Acute Worsening(0-9 weeks)
- HYP Change From Baseline to Week 9 in Average Manual Muscle Testing (MMT) Score(Baseline and 9 weeks)
- HOP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing Percent of Predicted Normal(Baseline and 9 weeks)
- HOP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing (MVICT) Scores(Baseline and 9 weeks)
- HYP Change From Baseline to Week 9 in SF-36 Mental Health Component Summary Score(Baseline and 9 weeks)
研究者
Robert Griggs, MD
Principal Investigator
University of Rochester