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

NCT ID: NCT00873392

Last Updated: 2013-12-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2013-05-31

Brief Summary

Medical treatment of idiopathic Parkinson disease motor symptoms requires dopaminergic drugs, with long term disabling side effects. (fluctuations, dyskinesia, ON/OFF phenomena). Use of nicotine in Parkinson's disease has been suggested by the lowest prevalence of smokers among Parkinsonian patients. However, controlled studies provided conflicting results. One of our patients showed a substantial decrease of his parkinsonian symptoms under transdermal nicotine-therapy. Currently, this patient has been treated since 8 years with an excellent safety, especially on cardiovascular level. Otherwise, the investigators performed an open pilot safety and feasibility study in 6 patients, which demonstrated the possibility of a controlled study. In this study, all patients received daily doses during several months until 105 mg/day and could, in parallel, decrease their L-Dopa and agonists doses, improving their motor scores.

The investigators now propose a phase II, controlled, single blind and randomised efficacy study (n=40) in 2 parallel groups. (1 group transdermal nicotine-therapy / 1 control group without additional therapy) The main objective is to verify the correlation between UPDRS (score III) motor score and the administrated nicotine dose. This study will also allow the evaluation of nicotine neuroprotective effect. The incrementation phase by weekly steps of 5 mg until 20 mg, then 10 mg to reach 90 mg/j or the maximal tolerated dose, will last on 11 weeks and will be followed by a 28 weeks phase at this stable dose. After this maximal dose "plateau phase", treatment will be progressively decreased by 15 mg weekly steps, over a de 6-week period followed by a five-week wash out phase.

Taking into account results from the pilot study, a long-term high doses treatment, seems to be liable to improve patients who deeply suffer from their disease. This is why the investigators now propose this monocentric institutional project.

Detailed Description

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,

Conditions

Idiopathic Parkinson's Disease

Keywords

Parkinson's disease; Motor fluctuation; Nicotine; Drug treatment; neuroprotection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Experimental drug

Group Type: EXPERIMENTAL

Transdermal nicotine

Intervention Type: DRUG

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

2

Usual treatment

Group Type: ACTIVE_COMPARATOR

Usual drug treatment of Parkinson's disease

Intervention Type: OTHER

Usual drug treatment of Parkinson's disease

Interventions

Transdermal nicotine

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

Intervention Type: DRUG

Usual drug treatment of Parkinson's disease

Usual drug treatment of Parkinson's disease

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre CESARO, PUPH

Role: PRINCIPAL_INVESTIGATOR

Groupe Hospitalier Albert Chenevier Henri Mondor

Locations

Groupe Hospitalier Albert Chenevier Henri Mondor

Créteil, , France

Countries

France

References

Villafane G, Cesaro P, Rialland A, Baloul S, Azimi S, Bourdet C, Le Houezec J, Macquin-Mavier I, Maison P. Chronic high dose transdermal nicotine in Parkinson's disease: an open trial. Eur J Neurol. 2007 Dec;14(12):1313-6. doi: 10.1111/j.1468-1331.2007.01949.x. Epub 2007 Oct 17.

Reference Type: RESULT

PMID: 17941858 (View on PubMed)

Other Identifiers

P 051031

Identifier Type: -

Identifier Source: org_study_id