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
Overview
- Phase
- Phase 2
- Intervention
- nicotine transdermal patch
- Conditions
- Parkinson's Disease
- Sponsor
- James BOYD MD
- Enrollment
- 160
- Locations
- 24
- Primary Endpoint
- 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).
- Last Updated
- 10 years ago
Overview
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.
Investigators
James BOYD MD
United States Principal Investigator
University of Vermont
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
Arms & Interventions
Transdermal nicotine patch
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.
Intervention: nicotine transdermal patch
Transdermal placebo patch
Subjects will apply a combination of 7 or 14 mg placebo transdermal patches until reaching their highest well tolerated dose.
Intervention: nicotine transdermal patch
Outcomes
Primary Outcomes
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).
Time Frame: From Baseline to week 60
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 Outcomes
- Parkinson's Disease Questionaire - 8(PDQ-8) that is calculated as the change between baseline and 60 weeks(Baseline and week 60)
- The 'time to initiation of a symptomatic treatment' is calculated from the date of randomization to the date that a subject initiates symptomatic therapy(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)
- 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(Baseline to week 52 and week 60)
- Parkinson's Disease Sleep Scale (PDSS) that is calculated as the change between baseline and week 52(baseline and week 52)
- The change in total UPDRS I-III score between baseline and 52 weeks (12 months)(Baseline to 52 weeks)
- Parkinson's Disease Questionnaire - 8 (PDQ-8), a patient completed questionaire, calculated as the change between baseline and week 52(Baseline and week 52)
- SCOPA-COG that is calculated as the change between baseline and 60 weeks(Baseline and week 60)
- The frequency of adverse events will be analyzed(Baseline through week 60)
- Scales for Outcomes of Parkinson's disease - Cognition (SCOPA-COG), is calculated as the change between baseline and week 52(Baseline and week 52)
- Beck Depression Inventory - II (BDI-II) that is calculated as the change between baseline and week 52(Baseline and week 52)
- BDI-II that is calculated as the change between baseline and 60 weeks(Baseline and Week 60)
- PDSS that is calculated as the change between baseline and week 60(Baseline and Week 60)