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Efficacy of Transdermal Nicotine, on Motor Symptoms in Advanced Parkinson's Disease (NICOPARK2)

Primary Purpose

Idiopathic Parkinson's Disease

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Transdermal nicotine
Usual drug treatment of Parkinson's disease
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Parkinson's Disease focused on measuring Parkinson's disease, Motor fluctuation, Nicotine, Drug treatment, neuroprotection

Eligibility Criteria

35 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Groupe Hospitalier Albert Chenevier Henri Mondor

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

Experimental drug

Usual treatment

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Evaluation of UPDRS III motor score assessed in "defined OFF" condition
Improvement of UPDRS III motor score assessed in "defined ON" condition
Evaluation of motor benefit (UPDRS "OFF" and "ON")
Evaluation of neuroprotection, (SPECT DaTSCAN and UPDRS "OFF")
Persistence of motor benefit (UPDRS "OFF" and "ON")
Decrease of total daily L-Dopa dose (or calculated equivalent in case of polytherapy)
Improvement of quality of life (ADL and PDQ 39 scales)
Decrease of daily percentage of "OFF" phase
Improvement of dyskinesia score, (UPDRS IV)
Relation dose / effect of nicotine
Estimation of the most effective and tolerated dose of nicotine per kg
Improvement of cognitive functions assessed by Mattis scale
Comparison of all parameters between the 2 groups of patients
Compliance to nicotine treatment
Tolerance of transdermal nicotine

Full Information

First Posted
March 31, 2009
Last Updated
December 29, 2013
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT00873392
Brief Title
Efficacy of Transdermal Nicotine, on Motor Symptoms in Advanced Parkinson's Disease
Acronym
NICOPARK2
Official Title
Efficacy of Transdermal Nicotine, on Motor Symptoms in Advanced Parkinson's Disease(One Daily Administration).A Controlled Randomised Study, in Two Parallel Groups and Single Blind in 40 Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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,

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Parkinson's Disease
Keywords
Parkinson's disease, Motor fluctuation, Nicotine, Drug treatment, neuroprotection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Experimental drug
Arm Title
2
Arm Type
Active Comparator
Arm Description
Usual treatment
Intervention Type
Drug
Intervention Name(s)
Transdermal nicotine
Intervention Description
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
Other
Intervention Name(s)
Usual drug treatment of Parkinson's disease
Intervention Description
Usual drug treatment of Parkinson's disease
Primary Outcome Measure Information:
Title
Comparison of motor scores in defined off condition : UPDRS III motor score assessed in "defined OFF" condition in comparison with control group.
Time Frame
after 20/39 weeks of treatment at maximal administered dose of nicotine
Secondary Outcome Measure Information:
Title
Evaluation of UPDRS III motor score assessed in "defined OFF" condition
Time Frame
after 20 weeks of treatment in comparison with control group
Title
Improvement of UPDRS III motor score assessed in "defined ON" condition
Time Frame
after a 12 hours discontinuation of antiparkinsonian treatments after 11, 20 and 39 weeks of treatment
Title
Evaluation of motor benefit (UPDRS "OFF" and "ON")
Time Frame
after a 28 weeks treatment period at stable dose of 90 mg
Title
Evaluation of neuroprotection, (SPECT DaTSCAN and UPDRS "OFF")
Time Frame
after 5 weeks of study treatment discontinuation
Title
Persistence of motor benefit (UPDRS "OFF" and "ON")
Time Frame
after 5 weeks of study treatment discontinuation
Title
Decrease of total daily L-Dopa dose (or calculated equivalent in case of polytherapy)
Time Frame
after 20 and 39 weeks of treatment
Title
Improvement of quality of life (ADL and PDQ 39 scales)
Time Frame
after 20 and 39 weeks of treatment
Title
Decrease of daily percentage of "OFF" phase
Time Frame
after 20 and 39 weeks of treatment
Title
Improvement of dyskinesia score, (UPDRS IV)
Time Frame
during the study
Title
Relation dose / effect of nicotine
Time Frame
end of the study
Title
Estimation of the most effective and tolerated dose of nicotine per kg
Time Frame
end of the study
Title
Improvement of cognitive functions assessed by Mattis scale
Time Frame
after 39 weeks of treatment
Title
Comparison of all parameters between the 2 groups of patients
Time Frame
after study treatment discontinuation, (Week 50)
Title
Compliance to nicotine treatment
Time Frame
during treatment
Title
Tolerance of transdermal nicotine
Time Frame
during the treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre CESARO, PUPH
Organizational Affiliation
Groupe Hospitalier Albert Chenevier Henri Mondor
Official's Role
Principal Investigator
Facility Information:
Facility Name
Groupe Hospitalier Albert Chenevier Henri Mondor
City
Creteil
ZIP/Postal Code
94000
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
17941858
Citation
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.
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Efficacy of Transdermal Nicotine, on Motor Symptoms in Advanced Parkinson's Disease

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