A randomized, placebo-controlled, multi-center study to assess the disease modifying potential of transdermal nicotine in early Parkinson's disease in Germany and the USA (NIC-PD)
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.
Active, not recruiting | Parkinson's Disease | Multisite
Exercise targeting cognitive impairment in Parkinsons disease
Mild cognitive impairment (MCI), particularly of the executive function (EF) subtype, is common in Parkinson's disease (PD) and transitions to dementia, increased fall risk, and poor quality of life. There is currently no effective treatment of MCI in PD. Our animal and clinical studies in PD demonstrate that skilled exercise facilitates neuroplasticity of the basal ganglia (BG), a brain region sub-serving EF and supports the hypothesis that exercise will reverse EF deficits in PD. Furthermore, recent studies in healthy aging support that skill-based exercise that specifically promotes motor skill fitness (MSF), compared with aerobic exercise that promotes cardiovascular fitness (CF), has a greater impact on EF and related BG circuits. The aim of this application is to compare and elucidate the effects of skill-based versus aerobic exercise versus control on MCI of the EF subtype in PD; we hypothesize that skill-based exercise will result in the greatest improvement in EF and lead to modification of underlying neural substrates. Individuals with PD and MCI will be assigned to 1 of 3 groups (N = 50/group) involving 36 1-hr sessions over 12 weeks including either: (i) skill-based exercise; (ii) aerobic exercise or (iii) social-contact control. Specific Aim 1 tests the hypothesis that skill-based exercise will lead to greater improvement in EF as indexed by standardized neurocognitive measures of EF. We will also compare pre-post exercise related changes on CF and EF. Secondary outcome measures will compare pre-post exercise effects on self- efficacy, quality of life (PDQ39) and Parkinson disease severity (MDS-UPDRS). Specific Aim 2 will test the hypothesis that skill-based will lead to greater gains in EF, compared to aerobic exercise or a control group on the ability to generalize task performance as indexed by a validated context-dependent motor learning (CDML) task. Specific Aim 3 will test the hypothesis that skill-based exercise will lead to greater gains in EF compared to aerobic exercise or a control group by examining improved Dual Task motor performance and the corresponding more efficient neural activity of brain regions sub-serving EF. DT capability will be performed during an fMRI scale. All assessments, that include motor skill and cardiovascular fitness, will be made at baseline and at 12 weeks (post-intervention); a 3-month follow up for EF in SA1 will be done.