Evaluate the Long-term (3 Months) Efficacy of L-threo DOPS (DroxiDopa) on Orthostatic Hypotension Symptoms and Other Non-motor Symptoms in Patients With Multiple System Atrophy (MSA). Comparative Study Versus Placebo
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 13
- 主要终点
- Evaluate the efficacy of long term efficacy of L-threo DOPS
研究概览
简要总结
Evaluate the effects of L-Threo DOPS on orthostatic hypotension symptoms and other non-motor symptoms in patients with Multiple System Atrophy (MSA) after 12 weeks following randomization to continued therapy with droxidopa or placebo.
详细描述
Background :
Multiple system atrophy (MSA) is a rare, sporadic progressive neurodegenerative disorder, rapidly leading to severe disability and impairment of quality of life. MSA is characterized by a variable combination of a poor levodopa parkinsonism and /or cerebellar ataxia and autonomic failure (cardiovascular and / or bladder and sexual dysfunction) (Gilman et al, 2008). The prevalence is approximately 4-5 cases per 100 000 inhabitants.
Orthostatic hypotension (OH) is one of the major symptoms of MSA, present in a large majority of patients, leading to significant disability because of impaired balance, falls and possibly syncope. Drugs available to treat OH in this disease are very limited.
L-ThreoDOPS (L DOPS or DroxiDopa) is an orally administered synthetic catecholamine acid that is converted to the sympathetic neurotransmitter norepinephrine (NE) through a single step of decarboxylation by the endogenous enzyme 3,4-dihydroxyphenylalanine (DOPA) decarboxylase. It prevents symptoms related to OH by central and/peripheral mechanisms. This drug is currently developed for "neurogenic OH" by Chelsea Therapeutics on the basis of short duration placebo-controlled randomized trials. Besides an expected effect on OH, L-DOPS may also, by noradrenergic stimulation, improve some motor and non-motor symptoms common and disabling in MSA patients such as akinesia and fatigue.
In this context, the French reference center for MSA and the 12 national centers with identified skills to manage this disease, propose to conduct a national multicenter randomized clinical trial versus placebo to evaluate the long term efficacy (3 months) of L-threo DOPS on the OH and other non-motor symptoms in MSA patients.
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
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •MSA patients (possible or probable, MSA-P or C (according to revised criteria, Gilman et al 2008)).
- •Aged 30 to 80 years,
- •Able to walk at least 10 meters
- •With symptomatic OH (score of at least 3 at one of the items of Part I of the OH scale (OHQ))
- •Documented fall in systolic blood pressure of at least 20 mmHg, and/or in diastolic blood pressure of at least 10 mmHg, within 3 minutes after standing.
- •Able to fill in the evaluation questionnaires with or without help
- •With no significant problems with swallowing.
- •Stable anti-parkinsonian, dysautonomia and depression treatments for the 4 weeks before the study and during the entire study
- •Signed written informed consent for the present study.
排除标准
- •Dementia (DSM-IV, Mini-Mental State Examination (MMSE) < 24/30)
- •Concomitant use of vaso-constrictive drugs, other than midodrine. Patients taking vasoconstrictor agents such as ephedrine, dihydroergotamine, must stop taking these drugs at least 2 days or 7 half-lives prior to their baseline visit (Visit 1); the association with midodrine may be kept at a stable dose not exceeding 3 tablets (7.5 mg) / day if the patient has no CV history. This will be discussed case by case with the coordinating center and the safety committee of this study.
- •Taking anti-hypertensive medication
研究组 & 干预措施
L-Threo DOPS
patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with L-Threo DOPS
干预措施: L-Threo DOPS (Drug)
placebo
patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with placebo
干预措施: placebo (Drug)
结局指标
主要结局
Evaluate the efficacy of long term efficacy of L-threo DOPS
时间窗: 12 weeks
Evaluate the efficacy of long term efficacy of L-threo DOPS (droxidopa) in MSA patients (probable or possible - cerebellar (C) or parkinsonian (P) type) with symptomatic NOH as measured by the relative change in mean score of Orthostatic Hypotension Symptom Assessment (OHSA) (Part I of the questionnaire on the symptoms OH (OHQ) (Kaufmann et al., 2011)) 12 weeks following randomization to therapy with droxidopa or placebo (including 8 weeks to maximum tolerated dose).
次要结局
- effects of L-Threo DOPS on motor symptoms(12 weeks)
- effect of L-Threo DOPS on dysautonomic symptoms(12 weeks)
- efficacy of L-ThreoDOPS on symptomatic OH(12 weeks)
- safety of high doses of L-ThreoDOPS(12 Weeks)