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

NCT ID: NCT01560754

Last Updated: 2015-09-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-12-31

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

nicotine transdermal patch

Intervention Type: DRUG

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.

Transdermal placebo patch

Subjects will apply a combination of 7 or 14 mg placebo transdermal patches until reaching their highest well tolerated dose.

Group Type: PLACEBO_COMPARATOR

nicotine transdermal patch

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Habitrol Transdermal patch (US); Nicotinell Transdermal patch (Germany)

Eligibility 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

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

Parkinson Study Group (PSG)

UNKNOWN

Sponsor Role: collaborator

International Parkinson Fonds Germany GmbH

INDUSTRY

Sponsor Role: collaborator

German Parkinson Study Group (GPS)

OTHER

Sponsor Role: collaborator

German Parkinson Society (DPG)

OTHER

Sponsor Role: collaborator

Philipps University Marburg

OTHER

Sponsor Role: collaborator

James BOYD MD

OTHER

Sponsor Role: lead

Responsible Party

James BOYD MD

United States Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Wolfgang Oertel, MD

Role: PRINCIPAL_INVESTIGATOR

Philipps-University Marburg, Germany / Global and German Principal Investigator

James Boyd, MD

Role: PRINCIPAL_INVESTIGATOR

University of Vermont / United States Principal Investigator

Locations

University of Southern California

Los Angeles, California, United States

The Parkinsons Institute

Sunnyvale, California, United States

Pacific Health Research & Education Institute

Honolulu, Hawaii, United States

The University of Kansas Medical Center

Kansas City, Kansas, United States

Struthers Parkinson'S Center

Golden Valley, Minnesota, United States

Feinstein Institute For Medical Research, North Shore-Lij Health System

Manhasset, New York, United States

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Vermont

Burlington, Vermont, United States

Universitatsklinikum Giessen U. Marburg GmbH

Standort Marburg, Marburg, Germany

Charite Campus Virchow Klinikum

Berlin, , Germany

Klinikum Bremerhaven

Bremerhaven, , Germany

Universitaetsklinikum CarlGustav Carus

Dresden, , Germany

Neurologische Klinik der, Dusseldorf

Düsseldorf, , Germany

Neurologische Universitaetsklinik Freiburg

Freiburg im Breisgau, , 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

München, , Germany

Universitaetsklinikum Tubingen

Tübingen, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

Countries

United States; Germany

References

Oertel WH, Muller HH, Unger MM, Schade-Brittinger C, Balthasar K, Articus K, Brinkman M, Venuto CS, Tracik F, Eberling J, Eggert KM, Kamp C, Kieburtz K, Boyd JT. Transdermal Nicotine Treatment and Progression of Early Parkinson's Disease. NEJM Evid. 2023 Sep;2(9):EVIDoa2200311. doi: 10.1056/EVIDoa2200311. Epub 2023 Aug 22.

Reference Type: DERIVED

PMID: 38320207 (View on PubMed)

Other Identifiers

KKS-135

Identifier Type: -

Identifier Source: org_study_id