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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Study of Methylphenidate to Treat Gait Disorders And Attention Deficit In Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicentric Trial

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

Detailed Summary:

Overall study duration: 2 years. Planned inclusion period: 12 months. Study duration for individual patients: 4 months and 2 weeks(2 weeks between screening and randomization, 3 months of double-blind treatment and then a 4-week wash-out period).

Primary objective (V1 and V4):

To assess efficacy of methylphenidate treatment on severe gait disorders including freezing assessed by the Stand Walk Sit Test in patients with advanced Parkinson's disease without dementia or depression and under subthalamic stimulation

Additional Efficacy Endpoints (V1 and V4):

  • Gait and motor symptoms: the "Freezing Of Gait trajectory", RGSE scale, the UPDRS scores (partI, II, III, IV), the dyskinesia rating scale
  • auto-questionnaires of Giladi, ABC scale and PDQ 39
  • Attention: simple and complex reactions times
  • Drowsiness: Epworth and Parkinson's disease Sleep Scales
  • Apathy Lille Apathy Rating Scale
  • Depression and other psychiatric disorders: MADRS, BPRS, MINI and psychiatric interview

Safety and Tolerability Endpoints (V1, V2, V3 and V4):

Tolerability Number of subjects (%) who discontinue the study Number of subjects (%) who discontinue the study due to AEs Safety Measures AE incidence Safety laboratory values Vital signs Blood pressure monitoring ECG Physical and neurological examination

Study Design:

Multicentric study: 12-week do
Sponsor: University Hospital, Lille

Current Primary Outcome: Number of steps on the Stand Walk Sit Test [ Time Frame: 3 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • time on the stand walk sit test [ Time Frame: 3 months ]
  • number of freezing on the FOG trajectory [ Time Frame: 3 months ]
  • UPDRS [ Time Frame: 3 months ]
  • RGSE [ Time Frame: 3 months ]
  • psychiatric interview [ Time Frame: 3 months ]
  • Cardiac examination with ECG and blood pressure [ Time Frame: 3 months ]


Original Secondary Outcome:

  • number of freezing ont the stand walk sit test [ Time Frame: 3 months ]
  • time on the stand walk sit test [ Time Frame: 3 months ]
  • FOG trajectory [ Time Frame: 3 months ]
  • UPDRS [ Time Frame: 3 months ]
  • RGSE [ Time Frame: 3 months ]
  • Achiron scale [ Time Frame: 3 months ]
  • psychiatric interview [ Time Frame: 3 months ]
  • Cardiac examination with ECG and blood pressure [ Time Frame: 3 months ]


Information By: University Hospital, Lille

Dates:
Date Received: June 2, 2009
Date Started: October 2009
Date Completion:
Last Updated: April 23, 2012
Last Verified: June 2009