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Parkinson's DiseasePhase 2NCT02680977

Mucuna Pruriens Therapy in Parkinson's Disease

A Phase 2 study testing MP-Equivalent, MP-Low and MP+DDCI in people with Parkinson's Disease, run by ASST Gaetano Pini-CTO at 1 site in Bolivia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Parkinson's Disease
What is being tested?
MP-Equivalent, MP-Low and MP+DDCI
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
18 participants
Where
1 siteBolivia
Study dates
Feb 2016to Sep 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Bolivia1 site

  • Clinica Niño Jesus

    Santa Cruz de la Sierra

Other trials in Bolivia

About this study

Official title: 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.

Read the 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.

Being tested
MP-Equivalent, MP-Low, MP+DDCI, LD+DDCI, LD-DDCI
Keywords
Mucuna pruriens, Levodopa
Medical subject headings
Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MP-EquivalentOther

    Also called Mucuna pruriens at equivalent dose than LD-DDCI

    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.

  • MP-LowOther

    Also called Mucuna pruriens at low dosage

    Mucuna pruriens powder at low dosage. The dose of MP is calculated to obtain a 3.5-fold Levodopa content than LD+DDCI

  • MP+DDCIOther

    Also called Mucuna pruriens plus Benserazide

    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.

  • LD+DDCIDrug

    Also called Madopar

    Levodopa plus Benserazide

  • LD-DDCIDrug

    Also called Levodopa without any DDCI (galenic formulation)

    Levodopa without any DDCI

  • PlaceboOther

    Groundnuts powder

Study groups in NCT02680977
Study groupRoleWhat they receive
MP-Equivalent; MP-Low; MP+DDCIExperimentalMP-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)
Receives: Other: MP-Equivalent; Other: MP-Low; Other: MP+DDCI
LD+DDCI; LD-DDCIActive comparatorLD+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.
Receives: Drug: LD+DDCI; Drug: LD-DDCI
PlaceboPlacebo comparatorPowder of groundnuts
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Magnitude of motor response

    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)

    Measured: up to 3 hours

Secondary outcomes (10)

  1. ON duration

    Duration of full ON state after acute intake

    Measured: up to 6 hours

  2. Latency to ON

    Latency in minutes between the acute intake (at the overnight OFF state) and the ON state

    Measured: up to 6 hours

  3. Severity of dyskinesias

    Severity of dyskinesias after acute intake, as assessed by the abnormal involuntary movements scale (AIMS) at 90 minutes and 180 minutes

    Measured: up to 3 hours

  4. Changes in vital signs

    Changes in blood pressure and heart rate at 90 minutes and 180 minutes after acute intake

    Measured: up to 3 hours

  5. Change in mean total daily off-time without troublesome dyskinesias

    Change in mean total daily off-time as measured by 24-h diaries during chronic treatment

    Measured: 16 weeks

  6. Change in quality of life questionnaire scores

    Change in quality of life (as assessed by the PDQ-39) during chronic treatment

    Measured: 16 weeks

  7. Change in Non-Motor Symptoms questionnaire scores

    Change in non-motor symptoms (as assessed by the Movement Disorders Society - Non-Motor Symptoms questionnaire) during chronic treatment

    Measured: 16 weeks

  8. Frequency of spontaneously reported adverse events

    Incidence of spontaneously reported adverse events during acute and chronic treatment

    Measured: 16 weeks

  9. Laboratory indices

    Changes in laboratory indices from baseline to week 16

    Measured: 16 weeks

  10. Electrocardiography

    Changes in electrocardiographic measures from baseline to week 16

    Measured: 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2016 (estimated)
  2. Study startFeb 2016
  3. Primary completionMay 2016
  4. Study completionSep 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02680977
Sponsor's protocol ID
SBN.SC.013/2015
Status last verified
Oct 2016
First submitted
9 Feb 2016
Last updated
5 Oct 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Katzenschlager R, Evans A, Manson A, Patsalos PN, Ratnaraj N, Watt H, Timmermann L, Van der Giessen R, Lees AJ. Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1672-7. doi: 10.1136/jnnp.2003.028761.

    PubMed 15548480

  • Lieu CA, Kunselman AR, Manyam BV, Venkiteswaran K, Subramanian T. A water extract of Mucuna pruriens provides long-term amelioration of parkinsonism with reduced risk for dyskinesias. Parkinsonism Relat Disord. 2010 Aug;16(7):458-65. doi: 10.1016/j.parkreldis.2010.04.015. Epub 2010 May 31.

    PubMed 20570206

  • Contin M, Lopane G, Passini A, Poli F, Iannello C, Guarino M. Mucuna pruriens in Parkinson Disease: A Kinetic-Dynamic Comparison With Levodopa Standard Formulations. Clin Neuropharmacol. 2015 Sep-Oct;38(5):201-3. doi: 10.1097/WNF.0000000000000098.

    PubMed 26366963

  • Poddighe S, De Rose F, Marotta R, Ruffilli R, Fanti M, Secci PP, Mostallino MC, Setzu MD, Zuncheddu MA, Collu I, Solla P, Marrosu F, Kasture S, Acquas E, Liscia A. Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease. PLoS One. 2014 Oct 23;9(10):e110802. doi: 10.1371/journal.pone.0110802. eCollection 2014.

    PubMed 25340511

  • Lieu CA, Venkiteswaran K, Gilmour TP, Rao AN, Petticoffer AC, Gilbert EV, Deogaonkar M, Manyam BV, Subramanian T. The Antiparkinsonian and Antidyskinetic Mechanisms of Mucuna pruriens in the MPTP-Treated Nonhuman Primate. Evid Based Complement Alternat Med. 2012;2012:840247. doi: 10.1155/2012/840247. Epub 2012 Sep 10.

    PubMed 22997535

  • Bega D, Gonzalez-Latapi P, Zadikoff C, Simuni T. A review of the clinical evidence for complementary and alternative therapies in Parkinson's disease. Curr Treat Options Neurol. 2014 Oct;16(10):314. doi: 10.1007/s11940-014-0314-5.

    PubMed 25143234

  • Manyam BV. Paralysis agitans and levodopa in "Ayurveda": ancient Indian medical treatise. Mov Disord. 1990;5(1):47-8. doi: 10.1002/mds.870050112.

    PubMed 2404203

  • Behari M, Bhatnagar SP, Muthane U, Deo D. Experiences of Parkinson's disease in India. Lancet Neurol. 2002 Aug;1(4):258-62. doi: 10.1016/s1474-4422(02)00105-9. No abstract available.

    PubMed 12849459

  • Ovallath S, Deepa P. The history of parkinsonism: descriptions in ancient Indian medical literature. Mov Disord. 2013 May;28(5):566-8. doi: 10.1002/mds.25420. Epub 2013 Mar 8.

    PubMed 23483637

  • Cilia R, Laguna J, Cassani E, Cereda E, Raspini B, Barichella M, Pezzoli G. Daily intake of Mucuna pruriens in advanced Parkinson's disease: A 16-week, noninferiority, randomized, crossover, pilot study. Parkinsonism Relat Disord. 2018 Apr;49:60-66. doi: 10.1016/j.parkreldis.2018.01.014. Epub 2018 Jan 11.

    PubMed 29352722

  • Cilia R, Laguna J, Cassani E, Cereda E, Pozzi NG, Isaias IU, Contin M, Barichella M, Pezzoli G. Mucuna pruriens in Parkinson disease: A double-blind, randomized, controlled, crossover study. Neurology. 2017 Aug 1;89(5):432-438. doi: 10.1212/WNL.0000000000004175. Epub 2017 Jul 5.

    PubMed 28679598

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MP-Equivalent, MP-Low and MP+DDCI in people with Parkinson's Disease, run by ASST Gaetano Pini-CTO at 1 site in Bolivia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Bolivia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Magnitude of motor response (time frame: up to 3 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02680977, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2016.

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