Mucuna Pruriens Therapy in Parkinson's Disease

October 4, 2016 updated by: Roberto Cilia, ASST Gaetano Pini-CTO

Mucuna Pruriens Therapy in Parkinson's Disease: a Double-blind, Placebo-controlled, Randomized, Crossover Study.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Preliminary Laboratory Test: The levodopa content in the powder obtained from roasted seeds of Bolivian black ecotype of MP was tested in a laboratory in Milan (Italy) and found to be 5.7%. No alkaloids or major antinutrients were found.

Objectives:

The primary objective is to assess the efficacy of acute challenge of MP roasted powder compared to Levodopa formulations with a dopa-decarboxylase inhibitor (LD-DDCI) and without (LD+DDCI), and placebo. Levodopa dose with DDCI is administered at 3.5 mg/kg, while Levodopa without DDCI is administered at the equivalent dose. This conversion factor is 5-fold, based on published studies comparing clinical and pharmacokinetic Levodopa effects with and without a DDCI and a previous double blind study on MP in patients with PD. For example, 100mg of Levodopa plus DDCI (either Benserazide or Carbidopa) corresponds to 500mg of Levodopa without any DDCI, obtained by administration of 8.75 grams of MP roasted powder (considering 5.7% of Levodopa in the bolivian ecotype of MP). Levodopa dose from MP is planned to be administered at not only at the equivalent dose of LD+DDCI (i.e. 5-fold), but also at the lower dosage of 3.5-fold.

Design: double-blind, randomized, placebo controlled, crossover study of acute response to levodopa-based therapies Duration: 3-6 hours for each treatment arm.

The secondary objectives include additional measures of efficacy of acute intake of MP as well as efficacy and safety of chronic use of MP as the only source of levodopa compared to optimized home LD+DDCI therapy. This latter part is performed after completion of the acute challenge part of the study.

Design: single-blind, randomized, crossover study of chronic response to levodopa-based therapies.

Duration: 8 weeks per treatment arm plus 3-week dose adjustment period. Initial levodopa-based therapy regimen (either MP therapy or Levodopa/Benserazide) may be adjusted for a period up to 3 weeks to optimize daily motor status during waking hours. After this period, patients enter the study and levodopa daily dose must be left unchanged throughout the 16-week course of the study.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bolivia
      • Santa Cruz de la Sierra, Bolivia
        • Clinica Niño Jesus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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)
Other: 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.
Other Names:
  • Mucuna pruriens at equivalent dose than LD-DDCI
Other: 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
Other Names:
  • Mucuna pruriens at low dosage
Other: MP+DDCI
Mucuna pruriens powder plus Benserazide. The dosage of MP is calculated to obtain the same Levodopa content than LD+DDCI. Benserazide is given as 1:4 ratio with Levodopa.
Other Names:
  • Mucuna pruriens plus Benserazide
Active Comparator: 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.
Drug: LD+DDCI
Levodopa plus Benserazide
Other Names:
  • Madopar
Drug: LD-DDCI
Levodopa without any DDCI
Other Names:
  • Levodopa without any DDCI (galenic formulation)
Placebo Comparator: Placebo
Powder of groundnuts
Other: Placebo
Groundnuts powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Magnitude of motor response
Time Frame: 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)
up to 3 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ON duration
Time Frame: up to 6 hours
Duration of full ON state after acute intake
up to 6 hours
Latency to ON
Time Frame: up to 6 hours
Latency in minutes between the acute intake (at the overnight OFF state) and the ON state
up to 6 hours
Severity of dyskinesias
Time Frame: up to 3 hours
Severity of dyskinesias after acute intake, as assessed by the abnormal involuntary movements scale (AIMS) at 90 minutes and 180 minutes
up to 3 hours
Changes in vital signs
Time Frame: up to 3 hours
Changes in blood pressure and heart rate at 90 minutes and 180 minutes after acute intake
up to 3 hours
Change in mean total daily off-time without troublesome dyskinesias
Time Frame: 16 weeks
Change in mean total daily off-time as measured by 24-h diaries during chronic treatment
16 weeks
Change in quality of life questionnaire scores
Time Frame: 16 weeks
Change in quality of life (as assessed by the PDQ-39) during chronic treatment
16 weeks
Change in Non-Motor Symptoms questionnaire scores
Time Frame: 16 weeks
Change in non-motor symptoms (as assessed by the Movement Disorders Society - Non-Motor Symptoms questionnaire) during chronic treatment
16 weeks
Frequency of spontaneously reported adverse events
Time Frame: 16 weeks
Incidence of spontaneously reported adverse events during acute and chronic treatment
16 weeks
Laboratory indices
Time Frame: 16 weeks
Changes in laboratory indices from baseline to week 16
16 weeks
Electrocardiography
Time Frame: 16 weeks
Changes in electrocardiographic measures from baseline to week 16
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ASST Gaetano Pini-CTO

Collaborators

Grisons Foundation for Parkinson's Disease

Investigators

  • Principal Investigator: Roberto Cilia, MD, ASST Gaetano Pini-CTO
  • Study Chair: Gianni Pezzoli, MD, ASST Gaetano Pini-CTO

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

May 1, 2016

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

February 9, 2016

First Submitted That Met QC Criteria

February 9, 2016

First Posted (Estimate)

February 12, 2016

Study Record Updates

Last Update Posted (Estimate)

October 5, 2016

Last Update Submitted That Met QC Criteria

October 4, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SBN.SC.013/2015

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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