Disease-modifying Potential of Transdermal NICotine in Early Parkinson's Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 October 2015
• Main ID: NCT01560754
• Date of registration: 09/03/2012
• Prospective Registration: Yes
• Primary sponsor: James BOYD MD
• Public title: Disease-modifying Potential of Transdermal NICotine in Early Parkinson's Disease NIC-PD
• Scientific 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
• Date of first enrolment: October 2012
• Target sample size: 160
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT01560754
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
• Phase: Phase 2

Countries of recruitment

Germany, United States

Contacts

• Name: Wolfgang Oertel, MD
• Affiliation: Philipps-University Marburg, Germany / Global and German Principal Investigator

• Name: James Boyd, MD
• Affiliation: University of Vermont / United States Principal Investigator

Key inclusion & exclusion 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

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, pseudo-myasthenic 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. nifedipine, 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



Age minimum: 30 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Parkinson's Disease

Intervention(s)

Drug: nicotine transdermal patch

Primary Outcome(s)

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]

Secondary Outcome(s)

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]

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]

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]

Beck Depression Inventory - II (BDI-II) that is calculated as the change between baseline and week 52 [Time Frame: Baseline and week 52]

Parkinson's Disease Questionaire - 8(PDQ-8) that is calculated as the change between baseline and 60 weeks [Time Frame: Baseline and week 60]

SCOPA-COG that is calculated as the change between baseline and 60 weeks [Time Frame: Baseline and week 60]

The frequency of adverse events will be analyzed [Time Frame: Baseline through week 60]

BDI-II that is calculated as the change between baseline and 60 weeks [Time Frame: Baseline and Week 60]

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]

The change in total UPDRS I-III score between baseline and 52 weeks (12 months) [Time Frame: Baseline to 52 weeks]

Parkinson's Disease Sleep Scale (PDSS) that is calculated as the change between baseline and week 52 [Time Frame: baseline and week 52]

PDSS that is calculated as the change between baseline and week 60 [Time Frame: Baseline and Week 60]

Secondary ID(s)

KKS-135

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Philipps-University Marburg, Germany

German Parkinson Society (DPG)

Michael J. Fox Foundation for Parkinson's Research

Parkinson Study Group (PSG)

German Parkinson Study Group (GPS)

International Parkinson Fonds (IPF)