High-dose transdermal nicotine in Parkinson's disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study

This is a fairly small study to assess the effect of transdermal nicotine on PD motor symptoms. I really like the video UPDRS rating approach with raters that were blind to the treatment groups... we have used similar methods in the past. However, I am only aware of anecdotes, and perhaps some animal models of PD, that suggest motor improvements in established PD brought about by nicotine... the tantalising study is to see if nicotine affects risk of PD... i.e. not symptom benefit, but neuroprotection....

Eur J Neurol. 2017 Sep 28. doi: 10.1111/ene.13474. [Epub ahead of print]
Villafane G, Thiriez C, Audureau E, Straczek C, Kerschen P, Cormier-Dequaire F, Van Der Gucht A, Gurruchaga JM, Quéré-Carne M, Evangelista E, Paul M, Defer G, Damier P, Remy P, Itti E, Fénelon G.

http://onlinelibrary.wiley.com/doi/10.1111/ene.13474/abstract

BACKGROUND: Studies of the effects of nicotine on motor symptoms in Parkinson's disease (PD) brought out discordant results. The aim of the present study was to evaluate the efficacy and safety of high doses of transdermal nicotine on motor symptoms in PD.

METHODS: Forty PD patients were randomly assigned to a treated and untreated arm in an open-label study. Treated patients received increasing doses of nicotine to reach 90 mg/day by 11 weeks. This dosage was maintained for 28 weeks (W39), and then reduced over six weeks. Final evaluation was performed six weeks after washout. The main outcome measure was the off-dopa UPDRS motor score measured on video recordings by raters blinded to the medication status of the patients.

RESULTS: There was no significant difference in off-dopa UPDRS motor scores between the nicotine-treated and non-treated groups, neither at W39 (19.4±9.3 vs. 21.5±14.2), nor considering W39 differences from baseline (-1.5±12.1 vs. +0.9±12.1). PDQ-39 scores decreased in nicotine-treated patients and increased in non-treated patients, but the difference was not significant. Overall tolerability was acceptable, and 12/20 treated patients reached the maximal dosage.

CONCLUSIONS: High doses of transdermal nicotine were tolerated, but our study failed to demonstrate significant improvement in UPDRS motor scores. Improvement in unblinded secondary outcomes (UPDRS-II, UPDRS-IV, doses of L-dopa-equivalents) suggest a possible benefit for patients treated with nicotine, which should be confirmed in larger double blind, placebo-controlled studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.