Mucuna Pruriens Therapy in Parkinson's Disease: a Double-blind, Placebo-controlled, Randomized, Crossover Study.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Magnitude of motor response
研究概览
简要总结
In low-income areas worldwide, most patients with Parkinson's disease (PD) cannot afford long-term Levodopa therapy. A potential therapeutic option for them is the use of a legume called Mucuna Pruriens var. Utilis (MP), which has seeds with a high levodopa content (5-6%) and grows in all tropical areas of the world. MP powder is very cheap (total annual cost for a PD patient: 10-15 US $). The aim of this study is to assess efficacy and tolerability of acute and chronic use of MP compared to standard Levodopa therapy.
The primary objective of this study is to investigate efficacy of acute levodopa challenge using MP in comparison to levodopa with a Dopa Decarboxylase Inhibitor (LD+DDCI) and without (LD-DDCI) and placebo.
The secondary objectives are to investigate safety of acute intake of MP as well as efficacy and safety of chronic intake of MP over a 8-week period in comparison to usual LD+DDCI home therapy.
详细描述
Background: Levodopa is the gold standard in the treatment of Parkinson's disease (PD). However, in low-income areas worldwide, most patients with PD cannot afford chronic therapy with levodopa. It is therefore mandatory to identify an interventional strategy designed to ease the economic burden of pharmacological management of PD in developing countries. A potential therapeutic option for them is the use of a legume called Mucuna Pruriens variant Utilis (MP), which has seeds containing high LD concentrations and grows spontaneously in all tropical and subtropical areas of the world, including South America, Africa and Asia. It is considered an invasive plant, as it grows rapidly without any particular measure needed to ensure its growth. The cost of home preparation of MP roasted powder is negligible and it is easy to store for a long time. LD was isolated from MP seeds for the first time in 1937 and its concentration therein was estimated to be 4-6%. MP is also known as Ayurvedic remedy for PD since ancient times.
Preliminary data: Published studies in parkinsonian rats, primates and humans suggest that MP may be used to improve PD motor symptoms without major side effects.
In a preliminary study, we analyzed 25 samples of MP from Africa, Latin America and Asia and measured the content in LD and anti-nutrients. We found that LD concentration in roasted powder samples was consistent with previous literature (median[Inter-Quartile Range] 5.3%[5.17-5.5]) and found no harmful anti-nutrients in all MP samples.
Study population: patients with diagnosis of idiopathic PD, including sustained response to levodopa and presence of motor fluctuations defined as predictable wearing-off, unpredictable ON-OFF fluctuations and sudden OFF periods.
Setting: Clinica Niño Jesus, Santa Cruz (Bolivia). This setting is chosen because the local neurologist Dr. Janeth Laguna has long-term experience on MP therapy in patients with PD (approximately 10 years). She started using MP because patients living in rural areas asked her to use this cheap source of LD to reduce the monthly cost of anti-PD therapy. In her experience, J.L. never recorded any serious adverse event (personal communication).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of idiopathic Parkinson's disease according to the United Kingdom Brain Bank criteria, defined by the presence of at least two of the cardinal signs of the disease (resting tremor, bradykinesia, rigidity) without any other known cause of parkinsonism.
- •Sustained response to levodopa and presence of motor fluctuations for at least 1 h every day during waking hours, defined as predictable wearing-off, unpredictable ON-OFF fluctuations and sudden OFF periods.
- •Patients had to receive optimum LD+DDCI, be stable for at least 30 days before baseline assessment.
- •Availability to written informed consent
排除标准
- •Cognitive impairment according to Mini-Mental State Examination < 26/30
- •Clinically significant psychiatric illness, including psychosis, major depression and addiction disorders (including compulsive levodopa intake).
- •Hoehn and Yahr stage of 5/5 in the medication-OFF state
- •Severe, unstable medical conditions (i.e. unstable diabetes mellitus, moderate to severe renal or hepatic impairment, neoplasms)
- •Risk of pregnancy
研究组 & 干预措施
MP-Equivalent; MP-Low; MP+DDCI
MP-Equivalent: Mucuna pruriens powder at equivalent dosage than LD+DDCI. The dose of MP is calculated to obtain a 5-fold Levodopa dose than LD+DDCI (for example 100mg of Madopar corresponds to 500mg of Levodopa in MP).
MP-Low: Mucuna pruriens powder at low dosage. The dose of MP is calculated to obtain a 3.5-fold Levodopa content than LD+DDCI (for example 100mg of Madopar corresponds to 350mg of Levodopa in MP) MP+DDCI: Mucuna pruriens powder plus Benserazide. The dosage of MP is calculated to obtain the same Levodopa content than LD+DDCI (for example 100mg of Madopar corresponds to 100mg of Levodopa in MP plus 25mg of Benserazide)
干预措施: MP-Equivalent (Other)
MP-Equivalent; MP-Low; MP+DDCI
MP-Equivalent: Mucuna pruriens powder at equivalent dosage than LD+DDCI. The dose of MP is calculated to obtain a 5-fold Levodopa dose than LD+DDCI (for example 100mg of Madopar corresponds to 500mg of Levodopa in MP).
MP-Low: Mucuna pruriens powder at low dosage. The dose of MP is calculated to obtain a 3.5-fold Levodopa content than LD+DDCI (for example 100mg of Madopar corresponds to 350mg of Levodopa in MP) MP+DDCI: Mucuna pruriens powder plus Benserazide. The dosage of MP is calculated to obtain the same Levodopa content than LD+DDCI (for example 100mg of Madopar corresponds to 100mg of Levodopa in MP plus 25mg of Benserazide)
干预措施: MP-Low (Other)
MP-Equivalent; MP-Low; MP+DDCI
MP-Equivalent: Mucuna pruriens powder at equivalent dosage than LD+DDCI. The dose of MP is calculated to obtain a 5-fold Levodopa dose than LD+DDCI (for example 100mg of Madopar corresponds to 500mg of Levodopa in MP).
MP-Low: Mucuna pruriens powder at low dosage. The dose of MP is calculated to obtain a 3.5-fold Levodopa content than LD+DDCI (for example 100mg of Madopar corresponds to 350mg of Levodopa in MP) MP+DDCI: Mucuna pruriens powder plus Benserazide. The dosage of MP is calculated to obtain the same Levodopa content than LD+DDCI (for example 100mg of Madopar corresponds to 100mg of Levodopa in MP plus 25mg of Benserazide)
干预措施: MP+DDCI (Other)
LD+DDCI; LD-DDCI
LD+DDCI: Levodopa plus Benserazide (dispersible formulation). The dose is calculated as 3.5mg per kg of body weight.
LD-DDCI: Levodopa without any dopa decarboxylase inhibitor (galenic formulation). The dose is 5-fold than LD+DDCI.
干预措施: LD+DDCI (Drug)
LD+DDCI; LD-DDCI
LD+DDCI: Levodopa plus Benserazide (dispersible formulation). The dose is calculated as 3.5mg per kg of body weight.
LD-DDCI: Levodopa without any dopa decarboxylase inhibitor (galenic formulation). The dose is 5-fold than LD+DDCI.
干预措施: LD-DDCI (Drug)
Placebo
Powder of groundnuts
干预措施: Placebo (Other)
结局指标
主要结局
Magnitude of motor response
时间窗: up to 3 hours
Percentage of change in UPDRS motor score (part III) from baseline (overnight OFF state) to 90 minutes and 180 minutes after acute intake (full ON state)
次要结局
- Change in quality of life questionnaire scores(16 weeks)
- Latency to ON(up to 6 hours)
- Severity of dyskinesias(up to 3 hours)
- Electrocardiography(16 weeks)
- ON duration(up to 6 hours)
- Changes in vital signs(up to 3 hours)
- Change in mean total daily off-time without troublesome dyskinesias(16 weeks)
- Frequency of spontaneously reported adverse events(16 weeks)
- Laboratory indices(16 weeks)
- Change in Non-Motor Symptoms questionnaire scores(16 weeks)
研究者
Roberto Cilia
Neurologist
ASST Gaetano Pini-CTO