Efficacy of Transdermal Nicotine, on Motor Symptoms in Advanced Parkinson's Disease

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,

Inclusion criteria

• Patients with idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB), since at least three years,or treated by L-dopa for 2 years minimum with motor fluctuations (amendment 12/10/2010)
• Patients aged between 35 and 70 years inclusive,
• L-Dopa responders: L-Dopa test with an improvement of over 30 % of UPDRS-III motor score,
• L-Dopa treatment since at least three years,
• Patients with Parkinson's disease stage maximum IV ("OFF" state) according to the modified Hoehn and Yahr classification (without treatment since at least 12 hours), and III maximum in "ON" state,
• Non smoker,
• Signed Informed Consent

Exclusion criteria

• Previous neurosurgery for Parkinson's disease,
• Weight < 45 kg or > 100 kg,
• Previous Parkinson's disease treatment by transdermal nicotine-therapy discontinued less than 6 months before inclusion,
• History of allergy to Nicotine,
• History of allergy to transdermal device,
• Cutaneous disorders wich could disturb use of transdermal device,
• Cognitive disorders, (Mattis score < 125)
• History or detection at inclusion of cardiac arrhythmia,
• History of coronary failure,
• History of cardiac failure, (NYHA from II to IV & ejection fraction (EF) < 40%)
• Severe arterial hypertension (diastolic > 100 mmHg) or uncontrolled,
• Symptomatic orthostatic hypotension, (2 points of differential in standing position and systolic <100mm Hg or clinical evidence)
• History of stroke or occlusive peripheral vascular disease,
• History of hyperthyroid,
• History or detection at inclusion of type I or II diabetes, (HbA1c < 11%)
• History of pulmonary disease: asthma, chronic obstructive pulmonary disease (COPD),
• History of auto-immune disease,
• Progressive depression, suicide attack, acute psychosis, invasive hallucinations, psychiatrist opinion harmful for a correct compliance to experimentation,
• History or recent gastroduodenal ulcer, (< 3 months)
• History or detection at inclusion of hepatobiliary or renal failure, (clearance< 60 mL/min)
• Pregnancy, breast-feeding,
• Absence of effective contraception in women in childbearing potential,
• Treatment by nifedipine, beta-blockers, diuretics, insulin and H2 antihistaminics for potential side effects in combination with nicotine,
• Patients unlikely to be compliant or to fully cooperate during the study.