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

Purpose

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).

Condition	Intervention	Phase
Parkinson's Disease	Drug: nicotine transdermal patch	Phase 2

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
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

Resource links provided by NLM:

Genetics Home Reference related topics: Parkinson disease Perry syndrome

MedlinePlus related topics: Parkinson's Disease

Drug Information available for: Nicotine tartrate Nicotine polacrilex

U.S. FDA Resources

Further study details as provided by University of Vermont:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 Outcome Measures:

The change in total UPDRS I-III score between baseline and 52 weeks (12 months) [ Time Frame: Baseline to 52 weeks ] [ Designated as safety issue: No ]
Parkinson's Disease Questionaire - 8(PDQ-8) that is calculated as the change between baseline and 60 weeks [ Time Frame: Baseline and week 60 ] [ Designated as safety issue: No ]
The frequency of adverse events will be analyzed [ Time Frame: Baseline through week 60 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Beck Depression Inventory - II (BDI-II) that is calculated as the change between baseline and week 52 [ Time Frame: Baseline and week 52 ] [ Designated as safety issue: Yes ]
Parkinson's Disease Sleep Scale (PDSS) that is calculated as the change between baseline and week 52 [ Time Frame: baseline and week 52 ] [ Designated as safety issue: Yes ]
SCOPA-COG that is calculated as the change between baseline and 60 weeks [ Time Frame: Baseline and week 60 ] [ Designated as safety issue: No ]
BDI-II that is calculated as the change between baseline and 60 weeks [ Time Frame: Baseline and Week 60 ] [ Designated as safety issue: Yes ]
PDSS that is calculated as the change between baseline and week 60 [ Time Frame: Baseline and Week 60 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	160
Study Start Date:	October 2012
Estimated Study Completion Date:	January 2015
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	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. Other Names: Habitrol Transdermal patch (US) Nicotinell Transdermal patch (Germany)
Placebo Comparator: Transdermal placebo patch Subjects will apply a combination of 7 or 14 mg placebo transdermal patches until reaching their highest well tolerated dose.	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. Other Names: Habitrol Transdermal patch (US) Nicotinell Transdermal patch (Germany)

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.

Eligibility

Ages Eligible for Study:	30 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
Previous history of allergic response to nicotine application or any of the patch excipients (see protocol sec. 10.2)
Previous history of allergic response to transdermal patches
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.)
Previous treatment with antiparkinsonian drugs (e.g. levodopa, dopamine agonists, etc.) other than MAO-B inhibitors
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
History of structural brain disease, cerebrovascular diseases
History of severe uncontrolled arterial hypertension
History of severe pulmonary disease (asthma, COPD)
History of auto-immune disease
History of Hyperthyroidism
History of Pheochromocytoma
History of seizures / epilepsy
History of amyosthenia / myasthenia gravis, pseudo-myasthenic syndrome
Dementia defined as Mini Mental State Examination (MMSE) score ≤ 24
Moderate depression (BDI-II score >24)
Suicide or suicide ideation
History or presence of specific psychiatric disorders, acute psychosis, hallucinations, pathologic gambling, alcohol or substance abuse
Patients under treatment with dihydropyridines (e.g. nifedipine, nicardipine, amlodipine)
History of uncontrolled diabetes
History of recent gastroduodenal ulcer (< 3 months) or presence of severe (acute and chronic) gastritis
History of known hepatobiliary or renal insufficiency
Pregnancy or lactation period
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01560754

Locations

United States, California
University of Southern California	Recruiting
Los Angeles, California, United States, 90033
Contact: CLARE BINLEY, RN 323-442-8029 clare.binley@med.usc.edu
Principal Investigator: MARK LEW, MD
The Parkinsons Institute	Recruiting
Sunnyvale, California, United States, 94085
Contact: Liza Reys, CCRP 408-542-5608 trials@thepi.org
Principal Investigator: GRACE LIANG, MD
United States, Hawaii
Pacific Health Research & Education Institute	Recruiting
Honolulu, Hawaii, United States, 96819
Contact: STEPHANIE TERASHITA, RN 808-433-7785 stephanie.terashita@va.gov
Principal Investigator: G WEBSTER ROSS, MD
United States, Kansas
The University of Kansas Medical Center	Recruiting
Kansas City, Kansas, United States, 66160
Contact: APRIL LANGHAMMER 913-588-6989 alanghammer@kumc.edu
Principal Investigator: RAJESH PAHWA, MD
United States, Minnesota
Struthers Parkinson`S Center	Recruiting
Golden Valley, Minnesota, United States, 55427
Contact: PATRICIA EDE, RN 952-993-2245 edepk@parknicollet.com
Principal Investigator: MARTHA NANCE, MD
United States, New York
Feinstein Institute For Medical Research, North Shore-Lij Health System	Recruiting
Manhasset, New York, United States, 11030
Contact: BARBARA SHANNON, RN 516-562-2905 bshannon@nshs.edu
Principal Investigator: ANDREW FEIGIN, MD
United States, Pennsylvania
Pennsylvania Hospital	Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: SUE REICHWEIN, CCRC 215-829-7273 sreichwein@pahosp.com
Principal Investigator: Howard Hurtig, MD
United States, Tennessee
Vanderbilt University Medical Center	Recruiting
Nashville, Tennessee, United States, 37232
Contact: DOROTHY SHEARON, RN 615-936-0219 dorothy.shearon@vanderbilt.edu
Principal Investigator: JOHN FANG, MD
United States, Vermont
University of Vermont	Recruiting
Burlington, Vermont, United States, 05405
Contact: EMILY HOUSTON 802-656-8974 emily.houston@uvm.edu
Principal Investigator: ROBERT HAMILL, MD
Germany
Universitatsklinikum Giessen U. Marburg GmbH	Recruiting
Standort Marburg, Marburg, Germany
Contact: Wolfgang H Oertel, Dr. Med. +06421/58-66278(0160903 14) oertelw@med.uni-marburg.de
Principal Investigator: Wolfgang Oertel, Prof.Dr. med
Charite Campus Virchow Klinikum	Recruiting
Berlin, Germany
Contact: Axel Lipp, Dr. med. +030450660326 axel.lipp@charite.de
Principal Investigator: Axel Lipp, Dr. med.
Klinikum Bremerhaven	Recruiting
Bremerhaven, Germany
Contact: Per Odin, Dr. med. 0471/299-3419 per.odin@klinikum-bremerhaven.de
Principal Investigator: Per Odin, Dr. med.
Universitaetsklinikum CarlGustav Carus	Recruiting
Dresden, Germany
Contact: Alexander Storch, Dr. med. +0351/4582532 alexander.storch@neuro.med.tu-dresden.de
Principal Investigator: Alexander Storch, Dr. med.
Neurologische Klinik der, Dusseldorf	Recruiting
Dusseldorf, Germany
Contact: Alfons Schnitzler, Dr. med. 02118118413 schnitza@uni-duesseldorf.de
Principal Investigator: Alfons Schnitzler, Dr. med.
Neurologische Universitaetsklinik Freiburg	Recruiting
Freiburg, Germany
Contact: Chrstian Winkler, Dr. med. 0761/270-50010 christian.winkler@uniklinik-freiburg.de
Principal Investigator: Christian Winkler, Dr. med.
Klinikum Hanau GmbH	Recruiting
Hanau, Germany
Contact: Horst Baas, Dr. med. +0618-296-6330 horst_baas@klinikum-hanau.de
Principal Investigator: Horst Baas, Prof.Dr. med
Universitaetsklinikum des Saarlandes	Recruiting
Homburg/Saar, Germany
Contact: Ulrich Dillmann, Dr. med. 06841/164136/4102 ulrich.dillmann@uks.eu
Principal Investigator: Ulrich Dillmann, Dr. med.
Paracelsus-Elena-Klinik Kassel	Recruiting
Kassel, Germany
Contact: Claudia Trenkwalder, Dr. Med +0561-6009-200 studien.trenkwalder@paracelsus-kliniken.de
Principal Investigator: Claudia Trenkwalder, Dr. med
Universitaetsklinikum Schlewsig-Holstein	Recruiting
Kiel, Germany
Contact: Gunther Deuschl, Dr. med +0431-591 8500 g.deuschl@neuologie.uni-kiel.de
Principal Investigator: Gunther Deuschl, Dr. med
Universitaetsklinikum Leipzig	Recruiting
Leipzig, Germany
Contact: Joseph Classen, Dr. med. 0341 97 24200 joseph.classen@medizin.uni-leipzig.de
Principal Investigator: Joseph Classen, Dr. med.
Klinikum rechts der Isar	Recruiting
Munchen, Germany
Contact: Gunter Hoglinger, Dr. med. 089-4140-4663 guenter.hoeglinger@DZNE.de
Principal Investigator: Gunter Hoglinger, Dr. med.
Universitaetsklinikum Tubingen	Recruiting
Tubingen, Germany
Contact: Daniela Berg, Dr. med. 07071/29-4490 daniela.berg@uni-tuebingen.de
Principal Investigator: Daniela Berg, Dr. med.
Universitaetsklinikum Ulm	Recruiting
Ulm, Germany
Contact: Jan Kassubek, Dr. med. 0731/500-63003 jan.kassubek@uni-ulm.de
Principal Investigator: Jan Kassubek, Dr. med.

Sponsors and Collaborators

James BOYD MD

Michael J. Fox Foundation for Parkinson's Research

Investigators

Principal Investigator:	James Boyd, MD	University of Vermont
Principal Investigator:	Wolfgang Oertel, MD	Philipps-University Marburg, Germany

More Information

No publications provided

Responsible Party:	James BOYD MD, Principal Investigator, US, University of Vermont
ClinicalTrials.gov Identifier:	NCT01560754 History of Changes
Other Study ID Numbers:	KKS-135
Study First Received:	March 9, 2012
Last Updated:	May 8, 2013
Health Authority:	United States: Food and Drug Administration Germany: Federal Institute for Drugs and Medical Devices European Union: European Medicines Agency

Keywords provided by University of Vermont:

Randomized
Placebo-controlled
Double-blind

Multi-center
Disease-modifying potential
transdermal nicotine

Additional relevant MeSH terms:

Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Nicotine
Nicotine polacrilex
Ganglionic Stimulants
Autonomic Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013

Disease-modifying Potential of Transdermal NICotine in Early Parkinson's Disease (NIC-PD)