NCT00873392

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Feb 2009

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2009

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 31, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 1, 2009

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2013

Completed
Last Updated

December 31, 2013

Status Verified

December 1, 2013

Enrollment Period

3.8 years

First QC Date

March 31, 2009

Last Update Submit

December 29, 2013

Conditions

Idiopathic Parkinson's Disease

Keywords

Parkinson's diseaseMotor fluctuationNicotineDrug treatmentneuroprotection

Outcome Measures

Primary Outcomes (1)

  • Comparison of motor scores in defined off condition : UPDRS III motor score assessed in "defined OFF" condition in comparison with control group.

    after 20/39 weeks of treatment at maximal administered dose of nicotine

Secondary Outcomes (15)

  • Evaluation of UPDRS III motor score assessed in "defined OFF" condition

    after 20 weeks of treatment in comparison with control group

  • Improvement of UPDRS III motor score assessed in "defined ON" condition

    after a 12 hours discontinuation of antiparkinsonian treatments after 11, 20 and 39 weeks of treatment

  • Evaluation of motor benefit (UPDRS "OFF" and "ON")

    after a 28 weeks treatment period at stable dose of 90 mg

  • Evaluation of neuroprotection, (SPECT DaTSCAN and UPDRS "OFF")

    after 5 weeks of study treatment discontinuation

  • Persistence of motor benefit (UPDRS "OFF" and "ON")

    after 5 weeks of study treatment discontinuation

  • +10 more secondary outcomes

Study Arms (2)

1

EXPERIMENTAL

Experimental drug

Drug: Transdermal nicotine

2

ACTIVE COMPARATOR

Usual treatment

Other: Usual drug treatment of Parkinson's disease

Interventions

Transdermal nicotineDRUG

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

1
Usual drug treatment of Parkinson's diseaseOTHER

Usual drug treatment of Parkinson's disease

2

Eligibility Criteria

Age35 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Previous neurosurgery for Parkinson's disease,
  • Weight \< 45 kg or \> 100 kg,
  • 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 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 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,
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Groupe Hospitalier Albert Chenevier Henri Mondor

Créteil, 94000, France

Location

Related Publications (1)

  • 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.

    PMID: 17941858RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

  • Pierre CESARO, PUPH

    Groupe Hospitalier Albert Chenevier Henri Mondor

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 31, 2009

First Posted

April 1, 2009

Study Start

February 1, 2009

Primary Completion

December 1, 2012

Study Completion

May 1, 2013

Last Updated

December 31, 2013

Record last verified: 2013-12

Locations

FR(1)