Back to resultsDisease-modifying Potential of Transdermal NICotine in Early Parkinson's Disease (NIC-PD)
Primary Purpose
Parkinson's Disease
Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
nicotine transdermal patch
Sponsored by
About this trial
This is an interventional prevention trial for Parkinson's Disease focused on measuring Randomized, Placebo-controlled, Double-blind, Multi-center, Disease-modifying potential, transdermal nicotine
Eligibility Criteria
Inclusion Criteria:
- Written informed consent
- Capability and willingness to comply with the study related procedures
- Age >/= 30 y
- Usage of effective contraception (see below) in fertile pre-menopausal female participants (from inclusion until end of wash out) Acceptable forms of effective contraception include established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception (condom or occlusive cap /diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository or male / female sterilization / or true abstinence.
- Diagnosis of PD according to the UK Brain Bank Diagnostic Criteria
- Early PD subjects within 18 months of diagnosis
- Hoehn and Yahr stage ≤ 2
- Patients not receiving or needing dopamine agonist or levodopa therapy presently or for the next year
- Stable treatment (>2 months) with MAO-B inhibitor (selegiline up to 10 mg/d or rasagiline up to 1 mg/d) allowable
Exclusion Criteria:
Clinical signs indicating a Parkinson syndrome other than idiopathic PD e.g.:
- Supranuclear gaze palsy
- Signs of frontal dementia
- History of repeated strokes with stepwise progression of Parkinsonian features
- History of repeated head injury or history of definite encephalitis
- Cerebellar signs
- Early severe autonomic involvement
- Babinski's sign
- History of exposure to or current treatment with neuroleptic drugs or anticraving substances
- History of nicotine use within five years of the baseline visit
- Previous history of allergic response to nicotine application or any of the patch excipients (see protocol sec. 10.2)
- Previous history of allergic response to transdermal patches
- Pre-existing dermatological disorder that could disturb transdermal patch application in the opinion of the investigator (e.g. generalized / systemic or local neurodermatitis, psoriasis, chronic dermatitis, urticaria, etc.)
- Previous treatment with antiparkinsonian drugs (e.g. levodopa, dopamine agonists, etc.) other than MAO-B inhibitors
History of unstable or serious cardiovascular diseases
- Unstable or worsening angina pectoris,
- History of recent myocardial infarction or cardiac failure (NYHA from II to IV), myocardial insufficiency
- History at inclusion of serious cardiac arrhythmia,
- History of recent stroke or occlusive peripheral vascular disease, vasospasm
- History of structural brain disease, cerebrovascular diseases
- History of severe uncontrolled arterial hypertension
- History of severe pulmonary disease (asthma, COPD)
- History of auto-immune disease
- History of Hyperthyroidism
- History of Pheochromocytoma
- History of seizures / epilepsy
- History of amyosthenia / myasthenia gravis, pseudo-myasthenic syndrome
- Dementia defined as Mini Mental State Examination (MMSE) score ≤ 24
- Moderate depression (BDI-II score >24)
- Suicide or suicide ideation
- History or presence of specific psychiatric disorders, acute psychosis, hallucinations, pathologic gambling, alcohol or substance abuse
- Patients under treatment with dihydropyridines (e.g. nifedipine, nicardipine, amlodipine)
- History of uncontrolled diabetes
- History of recent gastroduodenal ulcer (< 3 months) or presence of severe (acute and chronic) gastritis
- History of known hepatobiliary or renal insufficiency
- Pregnancy or lactation period
- Simultaneous participation or previous participation within 60 days before screening in another clinical drug or medical device study. Other Trials that do not affect the NIC-PD Study (NIT, health economics evaluations, questionnaires, genetic studies) could be allowed, but have to be approved and documented by the steering committee
Sites / Locations
- University of Southern California
- The Parkinsons Institute
- Pacific Health Research & Education Institute
- The University of Kansas Medical Center
- Struthers Parkinson'S Center
- Feinstein Institute For Medical Research, North Shore-Lij Health System
- Pennsylvania Hospital
- Vanderbilt University Medical Center
- University of Vermont
- Universitatsklinikum Giessen U. Marburg GmbH
- Charite Campus Virchow Klinikum
- Klinikum Bremerhaven
- Universitaetsklinikum CarlGustav Carus
- Neurologische Klinik der, Dusseldorf
- Neurologische Universitaetsklinik Freiburg
- Klinikum Hanau GmbH
- Universitaetsklinikum des Saarlandes
- Paracelsus-Elena-Klinik Kassel
- Universitaetsklinikum Schlewsig-Holstein
- Universitaetsklinikum Leipzig
- Otto-von-Guericke-Universitat
- Klinikum rechts der Isar
- Universitaetsklinikum Tubingen
- Universitaetsklinikum Ulm
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Transdermal nicotine patch
Transdermal placebo patch
Arm Description
Subjects will apply a combination of 7 or 14 mg nicotine transdermal patches until reaching their highest well tolerated dose of 7 to 28 mg/day.
Subjects will apply a combination of 7 or 14 mg placebo transdermal patches until reaching their highest well tolerated dose.
Outcomes
Primary Outcome Measures
The primary endpoint is calculated as the difference between the nicotine arm and the placebo arm in the change in total UPDRS I-III score between baseline and 60 weeks (14 months) (52 weeks treatment plus 8 weeks wash-out).
The primary objective is to demonstrate superiority measured by the difference between the nicotine arm and the placebo arm in the change in total UPDRS score (part I-III) between baseline and end of month 14 (12 months treatment and 2 months wash-out
Secondary Outcome Measures
The change in total UPDRS I-III score between baseline and 52 weeks (12 months)
Parkinson's Disease Questionaire - 8(PDQ-8) that is calculated as the change between baseline and 60 weeks
The frequency of adverse events will be analyzed
The 'time to initiation of a symptomatic treatment' is calculated from the date of randomization to the date that a subject initiates symptomatic therapy
Determine whether the slope of the curves for the total UPDRS score in active- and placebo-treated subjects show a tendency to converge over time
Parkinson's Disease Questionnaire - 8 (PDQ-8), a patient completed questionaire, calculated as the change between baseline and week 52
Scales for Outcomes of Parkinson's disease - Cognition (SCOPA-COG), is calculated as the change between baseline and week 52
Beck Depression Inventory - II (BDI-II) that is calculated as the change between baseline and week 52
Parkinson's Disease Sleep Scale (PDSS) that is calculated as the change between baseline and week 52
SCOPA-COG that is calculated as the change between baseline and 60 weeks
BDI-II that is calculated as the change between baseline and 60 weeks
PDSS that is calculated as the change between baseline and week 60
Full Information
NCT ID
NCT01560754
First Posted
March 9, 2012
Last Updated
September 28, 2015
Sponsor
James BOYD MD
Collaborators
Michael J. Fox Foundation for Parkinson's Research, Parkinson Study Group (PSG), International Parkinson Fonds Germany GmbH, German Parkinson Study Group (GPS), German Parkinson Society (DPG), Philipps University Marburg Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT01560754
Brief Title
Disease-modifying Potential of Transdermal NICotine in Early Parkinson's Disease
Acronym
NIC-PD
Official Title
A Randomized, Placebo-controlled, Double-blind, Multi-center Trial to Assess the Disease-modifying Potential of Transdermal Nicotine in Early Parkinson's Disease in Germany and the USA
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Unknown status
Study Start Date
October 2012 (undefined)
Primary Completion Date
August 2016 (Anticipated)
Study Completion Date
December 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
James BOYD MD
Collaborators
Michael J. Fox Foundation for Parkinson's Research, Parkinson Study Group (PSG), International Parkinson Fonds Germany GmbH, German Parkinson Study Group (GPS), German Parkinson Society (DPG), Philipps University Marburg Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study is to demonstrate that transdermal nicotine treatment retards disease progression as measured by change in total Unified Parkinson's Disease Rating Scale (UPDRS)(part I, II, III)score between baseline and after 52 weeks of study treatment plus two more months wash out (60 weeks).
Detailed Description
In order to prove the disease-modifying potential of transdermal nicotine treatment, an explanatory design with a 2 months wash-out phase before endpoint assessment will be performed. The primary objective is to demonstrate superiority measured by the difference between the nicotine arm and the placebo arm in the change in total UPDRS score (part I-III) between baseline and end of month 14 (12 months treatment and 2 months wash-out, see 3.1). The total UPDRS score will be determined by an independent rater, who is not involved in any other study-related procedure (e.g. reporting of adverse events). Change in total UPDRS score is the most widely applied measure in similar clinical trials assessing long-term beneficial effects of drugs. The investigators will also determine whether the slope of the curves for the total UPDRS score in active- and placebo-treated subjects show a tendency to converge over time. For this purpose the UPDRS will be determined three times after placebo/nicotine withdrawal at the end of the study during Visit 7,8, and 9 (i.e. four times including Visit 6).
Approximately 250 subjects will be screened at 25-30 centers in Germany and the USA. The recruitment period will be 18 months. In the screening phase, subjects will be evaluated for eligibility for enrolment into the treatment phase. The investigators expect that screening of 250 subjects will result in 160 eligible subjects who will be randomly assigned 1:1 to treatment with either transdermal nicotine or transdermal placebo patch.
The treatment phase consists of a titration period (16 weeks, to find the highest dosage tolerated by the subject with a target of 28 mg) and a maintenance period (week 17 to week 52 with the highest tolerated dosage of nicotine).
The treatment phase will be followed by an 8 week wash-out phase (3 weeks down titration and 5 weeks run out).
Dose adjustments are permitted for adverse events and have to be documented thoroughly.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Randomized, Placebo-controlled, Double-blind, Multi-center, Disease-modifying potential, transdermal nicotine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Transdermal nicotine patch
Arm Type
Experimental
Arm Description
Subjects will apply a combination of 7 or 14 mg nicotine transdermal patches until reaching their highest well tolerated dose of 7 to 28 mg/day.
Arm Title
Transdermal placebo patch
Arm Type
Placebo Comparator
Arm Description
Subjects will apply a combination of 7 or 14 mg placebo transdermal patches until reaching their highest well tolerated dose.
Intervention Type
Drug
Intervention Name(s)
nicotine transdermal patch
Other Intervention Name(s)
Habitrol Transdermal patch (US), Nicotinell Transdermal patch (Germany)
Intervention Description
Transdermal patches containing 7 or 14 mg nicotine or placebo with subjects titrating up until reaching their highest tolerated dose of 7 to 28mg/day.
Primary Outcome Measure Information:
Title
The primary endpoint is calculated as the difference between the nicotine arm and the placebo arm in the change in total UPDRS I-III score between baseline and 60 weeks (14 months) (52 weeks treatment plus 8 weeks wash-out).
Description
The primary objective is to demonstrate superiority measured by the difference between the nicotine arm and the placebo arm in the change in total UPDRS score (part I-III) between baseline and end of month 14 (12 months treatment and 2 months wash-out
Time Frame
From Baseline to week 60
Secondary Outcome Measure Information:
Title
The change in total UPDRS I-III score between baseline and 52 weeks (12 months)
Time Frame
Baseline to 52 weeks
Title
Parkinson's Disease Questionaire - 8(PDQ-8) that is calculated as the change between baseline and 60 weeks
Time Frame
Baseline and week 60
Title
The frequency of adverse events will be analyzed
Time Frame
Baseline through week 60
Title
The 'time to initiation of a symptomatic treatment' is calculated from the date of randomization to the date that a subject initiates symptomatic therapy
Time Frame
Baseline to initiation of symptomatic therapy, this timeframe will vary from subject to subject based on duration of disease and how well their PD is currently being managed
Title
Determine whether the slope of the curves for the total UPDRS score in active- and placebo-treated subjects show a tendency to converge over time
Time Frame
Baseline to week 52 and week 60
Title
Parkinson's Disease Questionnaire - 8 (PDQ-8), a patient completed questionaire, calculated as the change between baseline and week 52
Time Frame
Baseline and week 52
Title
Scales for Outcomes of Parkinson's disease - Cognition (SCOPA-COG), is calculated as the change between baseline and week 52
Time Frame
Baseline and week 52
Title
Beck Depression Inventory - II (BDI-II) that is calculated as the change between baseline and week 52
Time Frame
Baseline and week 52
Title
Parkinson's Disease Sleep Scale (PDSS) that is calculated as the change between baseline and week 52
Time Frame
baseline and week 52
Title
SCOPA-COG that is calculated as the change between baseline and 60 weeks
Time Frame
Baseline and week 60
Title
BDI-II that is calculated as the change between baseline and 60 weeks
Time Frame
Baseline and Week 60
Title
PDSS that is calculated as the change between baseline and week 60
Time Frame
Baseline and Week 60
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent
Capability and willingness to comply with the study related procedures
Age >/= 30 y
Usage of effective contraception (see below) in fertile pre-menopausal female participants (from inclusion until end of wash out) Acceptable forms of effective contraception include established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception (condom or occlusive cap /diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository or male / female sterilization / or true abstinence.
Diagnosis of PD according to the UK Brain Bank Diagnostic Criteria
Early PD subjects within 18 months of diagnosis
Hoehn and Yahr stage ≤ 2
Patients not receiving or needing dopamine agonist or levodopa therapy presently or for the next year
Stable treatment (>2 months) with MAO-B inhibitor (selegiline up to 10 mg/d or rasagiline up to 1 mg/d) allowable
Exclusion Criteria:
Clinical signs indicating a Parkinson syndrome other than idiopathic PD e.g.:
Supranuclear gaze palsy
Signs of frontal dementia
History of repeated strokes with stepwise progression of Parkinsonian features
History of repeated head injury or history of definite encephalitis
Cerebellar signs
Early severe autonomic involvement
Babinski's sign
History of exposure to or current treatment with neuroleptic drugs or anticraving substances
History of nicotine use within five years of the baseline visit
Previous history of allergic response to nicotine application or any of the patch excipients (see protocol sec. 10.2)
Previous history of allergic response to transdermal patches
Pre-existing dermatological disorder that could disturb transdermal patch application in the opinion of the investigator (e.g. generalized / systemic or local neurodermatitis, psoriasis, chronic dermatitis, urticaria, etc.)
Previous treatment with antiparkinsonian drugs (e.g. levodopa, dopamine agonists, etc.) other than MAO-B inhibitors
History of unstable or serious cardiovascular diseases
Unstable or worsening angina pectoris,
History of recent myocardial infarction or cardiac failure (NYHA from II to IV), myocardial insufficiency
History at inclusion of serious cardiac arrhythmia,
History of recent stroke or occlusive peripheral vascular disease, vasospasm
History of structural brain disease, cerebrovascular diseases
History of severe uncontrolled arterial hypertension
History of severe pulmonary disease (asthma, COPD)
History of auto-immune disease
History of Hyperthyroidism
History of Pheochromocytoma
History of seizures / epilepsy
History of amyosthenia / myasthenia gravis, pseudo-myasthenic syndrome
Dementia defined as Mini Mental State Examination (MMSE) score ≤ 24
Moderate depression (BDI-II score >24)
Suicide or suicide ideation
History or presence of specific psychiatric disorders, acute psychosis, hallucinations, pathologic gambling, alcohol or substance abuse
Patients under treatment with dihydropyridines (e.g. nifedipine, nicardipine, amlodipine)
History of uncontrolled diabetes
History of recent gastroduodenal ulcer (< 3 months) or presence of severe (acute and chronic) gastritis
History of known hepatobiliary or renal insufficiency
Pregnancy or lactation period
Simultaneous participation or previous participation within 60 days before screening in another clinical drug or medical device study. Other Trials that do not affect the NIC-PD Study (NIT, health economics evaluations, questionnaires, genetic studies) could be allowed, but have to be approved and documented by the steering committee
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolfgang Oertel, MD
Organizational Affiliation
Philipps-University Marburg, Germany / Global and German Principal Investigator
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James Boyd, MD
Organizational Affiliation
University of Vermont / United States Principal Investigator
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
The Parkinsons Institute
City
Sunnyvale
State/Province
California
ZIP/Postal Code
94085
Country
United States
Facility Name
Pacific Health Research & Education Institute
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96819
Country
United States
Facility Name
The University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Struthers Parkinson'S Center
City
Golden Valley
State/Province
Minnesota
ZIP/Postal Code
55427
Country
United States
Facility Name
Feinstein Institute For Medical Research, North Shore-Lij Health System
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Pennsylvania Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Vermont
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05405
Country
United States
Facility Name
Universitatsklinikum Giessen U. Marburg GmbH
City
Standort Marburg
State/Province
Marburg
Country
Germany
Facility Name
Charite Campus Virchow Klinikum
City
Berlin
Country
Germany
Facility Name
Klinikum Bremerhaven
City
Bremerhaven
Country
Germany
Facility Name
Universitaetsklinikum CarlGustav Carus
City
Dresden
Country
Germany
Facility Name
Neurologische Klinik der, Dusseldorf
City
Dusseldorf
Country
Germany
Facility Name
Neurologische Universitaetsklinik Freiburg
City
Freiburg
Country
Germany
Facility Name
Klinikum Hanau GmbH
City
Hanau
Country
Germany
Facility Name
Universitaetsklinikum des Saarlandes
City
Homburg/Saar
Country
Germany
Facility Name
Paracelsus-Elena-Klinik Kassel
City
Kassel
Country
Germany
Facility Name
Universitaetsklinikum Schlewsig-Holstein
City
Kiel
Country
Germany
Facility Name
Universitaetsklinikum Leipzig
City
Leipzig
Country
Germany
Facility Name
Otto-von-Guericke-Universitat
City
Magdeburg
ZIP/Postal Code
D-39120
Country
Germany
Facility Name
Klinikum rechts der Isar
City
Munchen
Country
Germany
Facility Name
Universitaetsklinikum Tubingen
City
Tubingen
Country
Germany
Facility Name
Universitaetsklinikum Ulm
City
Ulm
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Disease-modifying Potential of Transdermal NICotine in Early Parkinson's Disease
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