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

Parkinson's Disease Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01560754
• Other study ID #: KKS-135
• Status: Active, not recruiting
• Phase: Phase 2
• First received: March 9, 2012
• Last updated: September 28, 2015
• Start date: October 2012
• Est. completion date: December 2016

Study information

• Verified date: September 2015
• Source: University of Vermont
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: December 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• nicotine transdermal patch
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.

Locations

Country	Name	City	State
Germany	Charite Campus Virchow Klinikum	Berlin
Germany	Klinikum Bremerhaven	Bremerhaven
Germany	Universitaetsklinikum CarlGustav Carus	Dresden
Germany	Neurologische Klinik der, Dusseldorf	Dusseldorf
Germany	Neurologische Universitaetsklinik Freiburg	Freiburg
Germany	Klinikum Hanau GmbH	Hanau
Germany	Universitaetsklinikum des Saarlandes	Homburg/Saar
Germany	Paracelsus-Elena-Klinik Kassel	Kassel
Germany	Universitaetsklinikum Schlewsig-Holstein	Kiel
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Otto-von-Guericke-Universitat	Magdeburg
Germany	Klinikum rechts der Isar	Munchen
Germany	Universitatsklinikum Giessen U. Marburg GmbH	Standort Marburg	Marburg
Germany	Universitaetsklinikum Tubingen	Tubingen
Germany	Universitaetsklinikum Ulm	Ulm
United States	University of Vermont	Burlington	Vermont
United States	Struthers Parkinson`S Center	Golden Valley	Minnesota
United States	Pacific Health Research & Education Institute	Honolulu	Hawaii
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	University of Southern California	Los Angeles	California
United States	Feinstein Institute For Medical Research, North Shore-Lij Health System	Manhasset	New York
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	The Parkinsons Institute	Sunnyvale	California

Sponsors (7)

Lead Sponsor	Collaborator
James BOYD MD	German Parkinson Society (DPG), German Parkinson Study Group (GPS), International Parkinson Fonds Germany GmbH, Michael J. Fox Foundation for Parkinson's Research, Parkinson Study Group (PSG), Philipps University Marburg Medical Center

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	From Baseline to week 60	No
Secondary	The change in total UPDRS I-III score between baseline and 52 weeks (12 months)		Baseline to 52 weeks	No
Secondary	Parkinson's Disease Questionaire - 8(PDQ-8) that is calculated as the change between baseline and 60 weeks		Baseline and week 60	No
Secondary	The frequency of adverse events will be analyzed		Baseline through week 60	Yes
Secondary	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	No
Secondary	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	No
Secondary	Parkinson's Disease Questionnaire - 8 (PDQ-8), a patient completed questionaire, calculated as the change between baseline and week 52		Baseline and week 52	No
Secondary	Scales for Outcomes of Parkinson's disease - Cognition (SCOPA-COG), is calculated as the change between baseline and week 52		Baseline and week 52	No
Secondary	Beck Depression Inventory - II (BDI-II) that is calculated as the change between baseline and week 52		Baseline and week 52	Yes
Secondary	Parkinson's Disease Sleep Scale (PDSS) that is calculated as the change between baseline and week 52		baseline and week 52	Yes
Secondary	SCOPA-COG that is calculated as the change between baseline and 60 weeks		Baseline and week 60	No
Secondary	BDI-II that is calculated as the change between baseline and 60 weeks		Baseline and Week 60	Yes
Secondary	PDSS that is calculated as the change between baseline and week 60		Baseline and Week 60	Yes