Disease-modifying Potential of Transdermal NICotine in Early Parkinson's Disease

In order to prove the disease-modifying potential of transdermal nicotine treatment, an explanatory design with a 2 months wash-out phase before endpoint assessment will be performed. The primary objective is to demonstrate superiority measured by the difference between the nicotine arm and the placebo arm in the change in total UPDRS score (part I-III) between baseline and end of month 14 (12 months treatment and 2 months wash-out, see 3.1). The total UPDRS score will be determined by an independent rater, who is not involved in any other study-related procedure (e.g. reporting of adverse events). Change in total UPDRS score is the most widely applied measure in similar clinical trials assessing long-term beneficial effects of drugs. The investigators will also determine whether the slope of the curves for the total UPDRS score in active- and placebo-treated subjects show a tendency to converge over time. For this purpose the UPDRS will be determined three times after placebo/nicotine withdrawal at the end of the study during Visit 7,8, and 9 (i.e. four times including Visit 6). Approximately 250 subjects will be screened at 25-30 centers in Germany and the USA. The recruitment period will be 18 months. In the screening phase, subjects will be evaluated for eligibility for enrolment into the treatment phase. The investigators expect that screening of 250 subjects will result in 160 eligible subjects who will be randomly assigned 1:1 to treatment with either transdermal nicotine or transdermal placebo patch. The treatment phase consists of a titration period (16 weeks, to find the highest dosage tolerated by the subject with a target of 28 mg) and a maintenance period (week 17 to week 52 with the highest tolerated dosage of nicotine). The treatment phase will be followed by an 8 week wash-out phase (3 weeks down titration and 5 weeks run out). Dose adjustments are permitted for adverse events and have to be documented thoroughly.