Early PD subjects within 18 months of diagnosis and not expected to require dopamine agonist or levodopa therapy for 1 year, with Hoehn and Yahr stage 2 months) MAO-B inhibitor therapy allowed MedDRA version: 16.1 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Nicotinell 17,5 mg/24-Stunden-Pflaster
Product Name: Nicotinell
Pharmaceutical Form: Transdermal patch
CAS Number: 54-11-5
Other descriptive name: NICOTINE
Concentration unit: mg milligram
Sponsors
Philipps-University Marburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Capability and willingness to comply with the study related procedures 3. Age >=30 y 4. 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. 5. Diagnosis of PD according to the UK Brain Bank Diagnostic Criteria 6. Early PD subjects within 18 months of diagnosis 7. Hoehn and Yahr stage = 2 8. Patients not receiving or needing dopamine agonist or levodopa therapy presently or for the next year 9. Stable treatment (>2 months) with MAO-B inhibitor (selegiline up to 10 mg/d or rasagiline up to 1 mg/d) allowable Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. 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 2. History of exposure to or current treatment with neuroleptic drugs or anticraving substances 3. History of nicotine use within five years of the baseline visit 4. Previous history of allergic response to nicotine application or any of the patch excipients (see protocol sec. 10.2) 5. Previous history of allergic response to transdermal patches 6. 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.) 7. Previous treatment with antiparkinsonian drugs (e.g. levodopa, dopamine agonists, etc.) other than MAO-B inhibitors 8. 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 9. History of structural brain disease, cerebrovascular diseases 10. History of severe uncontrolled arterial hypertension 11. History of severe pulmonary disease (asthma, COPD) 12. History of auto-immune disease 13. History of Hyperthyroidism 14. History of Pheochromocytoma 15. History of seizures / epilepsy 16. History of amyosthenia / myasthenia gravis, pseudomyasthenic syndrome 17. Dementia defined as Mini Mental State Examination (MMSE) score = 24 18. Moderate depression (BDI-II score >24) 19. Suicide or suicide ideation 20. History or presence of specific psychiatric disorders, acute psychosis, hallucinations, pathologic gambling, alcohol or substance abuse 21. Patients under treatment with dihydropyridines (e.g. nifpedipine, nicardipine, amlodipine) 22. History of uncontrolled diabetes 23. History of recent gastroduodenal ulcer (< 3 months) or presence of severe (acute and chronic) gastritis 24. History of known hepatobiliary or renal insufficiency 25. Pregnancy or lactation period 26. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that transdermal nicotine treatment retards disease progression as measured by change in total (part I, II, III) UPDRS score between baseline and after 52 weeks of study treatment plus two more months wash out (60 weeks).;Timepoint(s) of evaluation of this end point: Baseline (T0), after 28 weeks (V4), after 40 weeks (V5), after 52 weeks (V6), after 56 weeks (V7), after 58 weeks (V8), after 60 weeks (V9) ;Secondary Objective: • • To demonstrate the effect of nicotine on total (part I, II, III) UPDRS score between baseline and after 52 weeks (12 months) of treatment. • to evaluate the effect on quality of life (Parkinson's Disease Questionnaire, PDQ-8), • to evaluate the effect on cognitive function (measured by SCOPA-COG (SCales for Outcomes of PArkinson's disease-COGnition)), • to evaluate the effect on mood (measured by the Beck Depression Inventory, BDI-II), • to evaluate the effect on sleep (measured by the Parkinson’s disease Sleep Scale, PDSS), • to determine and to compare the time to initiation of a symptomatic treatment (if deemed necessary), • to determine the total UPDRS score at the time of initiation of a dopaminergic treatment (if applicable), • to evaluate tolerability and safety, • to evaluate the incidence of adverse events. ;Primary end point(s): This study will assess the disease-modifying potential of transdermal nicotine treatment compared to placebo in early PD subjects over a treatment period of 12 months (52 weeks) treatment plus 2 months (8 weeks) wash-out: 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). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The change in total UPDRS I-III score between baseline and 52 weeks (12 months) is the endpoint for the first secondary objective Further secondary endpoints as PDQ-8, SCOPA-COG, BDI-II, and PDSS that are calculated as the change between baseline and 52 weeks as well as 60 weeks respectively, (52 weeks treatment plus 8 weeks wash-out). 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 of initiation. We 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. respectively, (52 weeks treatment plus 8 weeks wash-out). 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 of initiation. We 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. ;Timepoint(s) of evaluation of this end point: Baseline-V1(T0), V2(d1/W9), V3(d1/W17), V4(d1/W29), V5(d1/W41), V6(d1/W53), V7(d1/W57), V8(d1/W59), V9(d1/W61) | — |
Countries
Germany, United States
Contacts
Public ContactKKS Marburg
Philipps-Universität Marburg
Outcome results
None listed