Efficacy of Transdermal Nicotine, on Motor Symptoms in Advanced Parkinson's Disease
Condition: Idiopathic Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      Medical treatment of idiopathic Parkinson disease motor symptoms requires dopaminergic drugs,
      with long term disabling side effects. (fluctuations, dyskinesia, ON/OFF phenomena). Use of
      nicotine in Parkinson's disease has been suggested by the lowest prevalence of smokers among
      Parkinsonian patients. However, controlled studies provided conflicting results. One of our
      patients showed a substantial decrease of his parkinsonian symptoms under transdermal
      nicotine-therapy. Currently, this patient has been treated since 8 years with an excellent
      safety, especially on cardiovascular level. Otherwise, the investigators performed an open
      pilot safety and feasibility study in 6 patients, which demonstrated the possibility of a
      controlled study. In this study, all patients received daily doses during several months
      until 105 mg/day and could, in parallel, decrease their L-Dopa and agonists doses, improving
      their motor scores.

      The investigators now propose a phase II, controlled, single blind and randomised efficacy
      study (n=40) in 2 parallel groups. (1 group transdermal nicotine-therapy / 1 control group
      without additional therapy) The main objective is to verify the correlation between UPDRS
      (score III) motor score and the administrated nicotine dose. This study will also allow the
      evaluation of nicotine neuroprotective effect. The incrementation phase by weekly steps of 5
      mg until 20 mg, then 10 mg to reach 90 mg/j or the maximal tolerated dose, will last on 11
      weeks and will be followed by a 28 weeks phase at this stable dose. After this maximal dose
      "plateau phase", treatment will be progressively decreased by 15 mg weekly steps, over a de
      6-week period followed by a five-week wash out phase.

      Taking into account results from the pilot study, a long-term high doses treatment, seems to
      be liable to improve patients who deeply suffer from their disease. This is why the
      investigators now propose this monocentric institutional project.
    

Detailed description: 
      Experimental plan

      Phase II controled study, in 40 patients, randomised in single blind, and in 2 groups:

        -  One group treated by transdermal nicotine-therapy (N= 20),

        -  One group without additional therapy (N= 20).

      This study will consist in :

        -  One phase of weekly incrementations of dose during 11 weeks,

             -  Steps of 5 mg until 20 mg

             -  Then steps of 10 mg until the dose of 90mg or the maximal tolerated dose

        -  One stable dose phase, (90 mg or maximal tolerated dose) during 28 weeks,

        -  One phase of decrementing: treatment will be progressively decreased in a 6 weeks
           period,
    

Intervention name(s): Transdermal nicotine; Usual drug treatment of Parkinson's disease
Intervention type(s): Drug; Other
Intervention description(s): Steps of 5 mg until 20 mg Then steps of 10 mg until the dose of 90mg or the maximal tolerated dose One stable dose phase, (90 mg or maximal tolerated dose) during 28 weeks; Usual drug treatment of Parkinson's disease
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Parkinson's disease; Motor fluctuation; Nicotine; Drug treatment; neuroprotection