A Phase II Single Center, Randomized, Double Blind and Placebo Controlled Study Assessing the Safety, Tolerability and Effects of Progressively Increased Dose of Oral Mannitol in Parkinson's Disease
试验速览
- 阶段
- 2 期
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Safety of oral mannitol in Parkinson's disease as assessed by the number of mannitol-related adverse events, clinically significant changes in vital signs and clinically significant abnormalities in laboratory results.
研究概览
简要总结
Parkinson's disease is a progressive neurodegenerative disease that causes disabling motor and cognitive impairments. Currently, no disease-modifying therapy exists for this disease. Mannitol, a naturally-occurring substance, which is commonly used as sweetener, was offered as such agent. In this phase II, safety, tolerability-based dose finding, and efficacy study, mannitol or placebo (dextrose) in escalating doses will be given to patients with Parkinson's disease for 36 weeks.
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
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and signing of informed consent form.
- •Age 40-75 years at the day of visit
- •Diagnosis of Parkinson's disease that is based on the United Kingdom brain bank criteria diagnosed after the age of
- •Stable regime of anti-parkinsonian medication for at least 4 weeks at the day of visit 1.
排除标准
- •Patients with motor deficits that require administration of symptomatic therapy more than 4 times per day at the day of visit
- •Patients on advanced therapy for Parkinson's disease (sub-cutaneous apomorphine, deep brain stimulation or intra-jejunal levodopa infusion).
- •Patients with dementia reflected by a Mini-mental state examination (MoCA) ≥
- •Patient with legal guardian.
- •History of psychosis or use of dopamine receptor blocking agent on the year proceeding at the visit
- •Quetiapine at dose lower or equal 50 mg per day prescribed for indication other than psychosis is allowed.
- •Suspected Parkinsonian syndrome other than Parkinson's disease.
- •Use of medical marihuana on the month proceeding visit
- •Pregnant or lactating women, or fertile woman who does not use contraceptive. Woman of child-bearing potential must have a negative urine Human chorionic gonadotropin (hCG) and will be monitored by repeated urine tests.
- •Patient with significantly impaired renal functions (urea or creatinine values 20% above the upper norm limit).
- •Diabetes mellitus.
- •Clinical evidence for congestive heart failure.
- •Patient with symptomatic orthostatic hypotension.
- •Based on investigator's opinion, any medical condition that may progress due to consumption of oral mannitol or glucose.
研究组 & 干预措施
D-Mannitol
Oral Supplement of the investigated substance: D-Mannitol powder (manufacturer Roquette)
干预措施: Oral D-Mannitol of Placebo (Dietary Supplement)
Placebo
Oral Supplement of the placebo: Dextrose monohydrate powder (manufacturer Roquette)
干预措施: Oral D-Mannitol of Placebo (Dietary Supplement)
结局指标
主要结局
Safety of oral mannitol in Parkinson's disease as assessed by the number of mannitol-related adverse events, clinically significant changes in vital signs and clinically significant abnormalities in laboratory results.
时间窗: 36 weeks
Safety will be assessed by the number of treatment-related adverse events, number of patients with clinically significant change of vital signs (supine and standing blood pressure and pulse) and number of patients with clinically significant change in laboratory results (electrolytes, renal and liver functions, blood count).
Tolerability of oral mannitol in Parkinson's disease as assessed by the maximal daily dose (in grams) of mannitol that does not cause discomfort.
时间窗: 36 weeks
Tolerability of oral mannitol in Parkinson's disease as assessed by the maximal daily dose (in grams, up to 18 grams per day) of mannitol that does not cause discomfort based on the subjective report by the patient.
次要结局
- Change of Brief Smell Identification Test (B-SIT) score between baseline and week 36.(36 weeks)
- Change in constipation assesment (CAS) score between baseline and week 36.(36 weeks)
- Time-interval for starting symptomatic therapy (in days) between baseline and week 36, in patients not receiving symptomatic therapy at baseline.(36 weeks)
- Change in levodopa-equivalent dose units between baseline and week 36.(36 weeks)
- Change in Montreal Cognitive Assessment (MoCA) test score between baseline and week 36.(36 weeks)
- Change in the ratio of total-to-proteinase K-resistant α-synuclein in red blood cells (RBC) measured by enzyme-linked immunosorbent assay (ELISA)between baseline and week 36.(36 weeks)
- Change in non-motor symptoms of Parkinson's disease scale (NMSS) between baseline and week 36.(36 weeks)
研究者
ARKADIR DAVID
Principal Investigator
Hadassah Medical Organization