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

Abstract

Background and purpose: 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 6 weeks. Final evaluation was performed 6 weeks after washout. The main outcome measure was the OFF-DOPA Unified Parkinson's Disease Rating Scale (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 AE 9.3 vs. 21.5 AE 14.2) nor considering W39 differences from baseline (À1.5 AE 12.1 vs. +0.9 AE 12.1). The 39-item Parkinson's disease questionnaire 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.

Breathable Nanowood Biofilms as Guiding Layer for Green On‐Skin Electronics

“…Similarly, the porous delignified biofilm also exhibits slightly higher transparency than original wood slice (Figure b), due to the elimination of light absorption as the colored lignin was removed . Overall, the enhanced transparency makes our biofilms more cosmetically acceptable and also facilitates the observation of the skin condition such as the side effects (redness, dermatitis, etc) of feedback transdermal therapy of On‐skinE.…”

“…Besides, human skin is also the largest therapeutic interface, the transdermal therapy is now one of the most useful ways to deliver a drug systemically for treating many diseases (such as emesia, Parkinson's disease, cancer, and diabetes mellitus). As seen in Figure g, our biofilms guide the directional flow of artificial sweat to trigger the lighting of LEDs with higher brightness than the original wood slice.…”

The Effect of L-dopa on Postural Stability in Parkinson’s Disease Patients

“…However, the occurrence of motor and postural complications (on average, in about 50% of patients after 3-5 years of treatment with this drug) hinder the functioning of a patient [20]. Posture-and motor-related disorders are accompanied by fluctuations in symptoms beyond motor sensory, autonomic and neuropsychiatric symptoms [21][22][23].…”

Disease‐modifying approaches for Parkinson disease

“…Epidemiological observations showing a lower prevalence of Parkinson disease among smokers and caffeine drinkers has led to ongoing trials assessing nicotine (http://ClinicalTrials.gov identifier: NCT01560754) and caffeine (NCT01738178). While the data regarding disease modification from these trials have not yet been reported, both approaches have recently returned null results in relation to symptomatic benefits in Parkinson disease 6 , 7 . One other recently reported significant epidemiological observation highlighted that people who had been prescribed β‐agonist medications for asthma (eg, salbutamol) had lower rates of Parkinson disease, whereas increased rates of Parkinson disease were seen in patients taking a β‐blocker for hypertension (eg, propranolol) 8 .…”