Study of Methylphenidate to Treat Gait Disorders And Attention Deficit In Parkinson's Disease (PARKGAIT-II)

NCT00914095 | Completed Phase 4 DMC

• 4 other identifiers: 2008-005801-202008_25/0832PHRC 2008/1918A90135-48
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

Therapeutic management of gait disorders in very advanced Parkinson's disease (PD) patients can sometimes be disappointing, since dopaminergic drug treatments and subthalamic nucleus (STN) stimulation are more effective for limb-related Parkinsonian signs than for gait disorders. Gait disorders could be also partly related to noradrenergic system impairment, pharmacological modulation of both dopamine and noradrenaline pathways could potentially improve the symptomatology. The investigators have demonstrated using an open label study on 17 advanced PD patients that chronic, high doses of methylphenidate (MPD) improved gait, freezing of gait, motor symptoms and attention in the absence of L-Dopa and increased the intensity of response of these symptoms to L-Dopa (Devos et al., 2007). The investigators aimed to confirm their results using a randomized, double-blind, placebo-controlled, parallel-group, multicentric trial. The investigators will assess the clinical value of chronic, high doses (1 mg/kg/day) of MPD vs placebo in 88 non demented PD patients suffering from severe gait disorders with freezing despite their use of optimal dopaminergic doses and eventually STN stimulation parameters. Efficacy will be assessed directly and on video in the absence of L-Dopa and again after acute administration of the drug, both before and after a 3-month course of MPD, using Stand Walk Sit test (primary criteria), the "Freezing Of Gait trajectory", RGSE scale, the UPDRS scores, the dyskinesia rating scale, Achiron scales and using auto-questionnaires of Giladi, ABC scale and PDQ 39. Attention will be assessed using reactions times. Drowsiness will be assessed using Epworth and Parkinson's disease Sleep Scales. Apathy and depression will be monitored with Lille Apathy Rating Scale, MADRS, BPRS, MINI and psychiatric interview. Cardiologic and general tolerance will be also monitored. This study could lead to propose methylphenidate with a good efficacy/ risk balance in advanced PD patients suffering from severe gait disorders with freezing of gait, drowsiness and attention deficit.

Conditions

Gait Disorders, Neurologic; Dementia; Parkinson's Disease

Keywords

Parkinson's disease; Freezing of Gait; Methylphenidate; Dopamine transporter inhibitor; Noradrenaline

Outcome Measures

Primary Outcomes (1)

• Number of steps on the Stand Walk Sit Test

  3 months

Secondary Outcomes (6)

• time on the stand walk sit test

  3 months

• number of freezing on the FOG trajectory

  3 months

• UPDRS

  3 months

• RGSE

  3 months

• psychiatric interview

  3 months

Study Arms (2)

methylphenidate

ACTIVE COMPARATOR

methylphenidate 10 mg tablets (1 mg /kg /day) 3 time a day

Drug: methylphenidate

placebo

PLACEBO COMPARATOR

tablets of placebo 3 time a day

Drug: placebo

Interventions

methylphenidate DRUG

10 mg tablet of methylphenidate 3 times a day (1 mg/kg/day)

Also known as: Concerta, Ritaline

methylphenidate

placebo DRUG

tablets of placebo 3 times a day

placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parkinson's disease of more than 5 years
• Subthalamic nucleus stimulation
• Gait disorders impeding moderately to severely the activities of daily living
• gait disorders including freezing of gait
• able to walk without physical assistance

You may not qualify if:

• Dementia (MMSE \< 27 et score de Mattis \< 130)
• Requiring dopatherapie modification
• Requiring subthalamic stimulation parameters adaptation
• Psychiatric disorders: hallucinations, unstable thymic disorders, psychosis)
• Cardiac disorders: dysrhythmia or unstable arterial hypertension
• Unstable or severe medical illness
• intolerance or contraindication to methylphenidate

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

Service de Neurologie, Clinique Neurologique, EA 2683, IFR 114

Lille, 59037, France

Location

Related Publications (4)

• Devos D, Krystkowiak P, Clement F, Dujardin K, Cottencin O, Waucquier N, Ajebbar K, Thielemans B, Kroumova M, Duhamel A, Destee A, Bordet R, Defebvre L. Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson's disease. J Neurol Neurosurg Psychiatry. 2007 May;78(5):470-5. doi: 10.1136/jnnp.2006.100016. Epub 2006 Nov 10.

  PMID: 17098845 BACKGROUND

• Moreau C, Delval A, Defebvre L, Dujardin K, Duhamel A, Petyt G, Vuillaume I, Corvol JC, Brefel-Courbon C, Ory-Magne F, Guehl D, Eusebio A, Fraix V, Saulnier PJ, Lagha-Boukbiza O, Durif F, Faighel M, Giordana C, Drapier S, Maltete D, Tranchant C, Houeto JL, Debu B, Sablonniere B, Azulay JP, Tison F, Rascol O, Vidailhet M, Destee A, Bloem BR, Bordet R, Devos D; Parkgait-II study group. Methylphenidate for gait hypokinesia and freezing in patients with Parkinson's disease undergoing subthalamic stimulation: a multicentre, parallel, randomised, placebo-controlled trial. Lancet Neurol. 2012 Jul;11(7):589-96. doi: 10.1016/S1474-4422(12)70106-0. Epub 2012 Jun 1.

  PMID: 22658702 RESULT

• Moreau C, Meguig S, Corvol JC, Labreuche J, Vasseur F, Duhamel A, Delval A, Bardyn T, Devedjian JC, Rouaix N, Petyt G, Brefel-Courbon C, Ory-Magne F, Guehl D, Eusebio A, Fraix V, Saulnier PJ, Lagha-Boukbiza O, Durif F, Faighel M, Giordana C, Drapier S, Maltete D, Tranchant C, Houeto JL, Debu B, Azulay JP, Tison F, Destee A, Vidailhet M, Rascol O, Dujardin K, Defebvre L, Bordet R, Sablonniere B, Devos D; Parkgait-II Study Group. Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease. Brain. 2015 May;138(Pt 5):1271-83. doi: 10.1093/brain/awv063. Epub 2015 Mar 23.

  PMID: 25805645 DERIVED

• Dujardin K, Tard C, Duhamel A, Delval A, Moreau C, Devos D, Defebvre L. The pattern of attentional deficits in Parkinson's disease. Parkinsonism Relat Disord. 2013 Mar;19(3):300-5. doi: 10.1016/j.parkreldis.2012.11.001. Epub 2012 Nov 27.

  PMID: 23196037 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Gait Disorders, Neurologic; Dementia

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David Devos, MD, PhD

  Service de Neurologie, Clinique Neurologique, EA 2683, IFR 114, IMPRT

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2009
• First Posted: June 4, 2009
• Study Start: October 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 14, 2026

Record last verified: 2009-06

Locations

FR (1)