Mucuna Pruriens Therapy in Parkinson's Disease

NCT02680977 | Completed Phase 2

• 1 other identifier: SBN.SC.013/2015
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Parkinson's Disease

Keywords

Mucuna pruriens; Levodopa

Outcome Measures

Primary Outcomes (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)

  up to 3 hours

Secondary Outcomes (10)

• ON duration

  up to 6 hours

• Latency to ON

  up to 6 hours

• Severity of dyskinesias

  up to 3 hours

• Changes in vital signs

  up to 3 hours

• Change in mean total daily off-time without troublesome dyskinesias

  16 weeks

Study Arms (3)

MP-Equivalent; MP-Low; MP+DDCI

EXPERIMENTAL

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; Other: MP-Low; Other: MP+DDCI

LD+DDCI; LD-DDCI

ACTIVE COMPARATOR

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; Drug: LD-DDCI

Placebo

PLACEBO COMPARATOR

Powder of groundnuts

Other: Placebo

Interventions

MP-Equivalent OTHER

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.

Also known as: Mucuna pruriens at equivalent dose than LD-DDCI

MP-Equivalent; MP-Low; MP+DDCI

MP-Low OTHER

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

Also known as: Mucuna pruriens at low dosage

MP-Equivalent; MP-Low; MP+DDCI

MP+DDCI OTHER

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.

Also known as: Mucuna pruriens plus Benserazide

MP-Equivalent; MP-Low; MP+DDCI

LD-DDCI DRUG

Levodopa without any DDCI

Also known as: Levodopa without any DDCI (galenic formulation)

LD+DDCI; LD-DDCI

Placebo OTHER

Groundnuts powder

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ASST Gaetano Pini-CTO: lead
• Grisons Foundation for Parkinson's Disease: collaborator

Study Sites (1)

Clinica Niño Jesus

Santa Cruz de la Sierra, Bolivia

Location

Related Publications (11)

• 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.

  PMID: 15548480 BACKGROUND

• 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.

  PMID: 20570206 BACKGROUND

• 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.

  PMID: 26366963 BACKGROUND

• 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.

  PMID: 25340511 BACKGROUND

• 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.

  PMID: 22997535 BACKGROUND

• 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.

  PMID: 25143234 BACKGROUND

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

  PMID: 2404203 BACKGROUND

• 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.

  PMID: 12849459 BACKGROUND

• 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.

  PMID: 23483637 BACKGROUND

• 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.

  PMID: 29352722 DERIVED

• 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.

  PMID: 28679598 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Benserazide; benserazide, levodopa drug combination; Levodopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Dihydroxyphenylalanine; Catecholamines; Amines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Roberto Cilia, MD

  ASST Gaetano Pini-CTO

  PRINCIPAL INVESTIGATOR

• Gianni Pezzoli, MD

  ASST Gaetano Pini-CTO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: February 9, 2016
• First Posted: February 12, 2016
• Study Start: February 1, 2016
• Primary Completion: May 1, 2016
• Study Completion: September 1, 2016
• Last Updated: October 5, 2016

Record last verified: 2016-10

Locations

BO (1)