Efficacy of Orally Disintegrating Selegiline in Parkinson's Patients Experiencing Adverse Effects With Dopamine Agonists

Condition(s) targeted: Parkinson's Disease

Intervention: orally disintegrating selegiline (Zelapar) (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Parkinson's Disease and Movement Disorder Center of Boca Raton

Official(s) and/or principal investigator(s):
Rajesh Pahwa, MD, Principal Investigator, Affiliation: University of Kansas

The purpose of the study is to determine if reducing or eliminating a dopamine agonist causing one of the side effects of daytime sleepiness, swelling of the lower legs or feet, hallucinations or impulsive behaviors while adding orally disintegrating selegiline can eliminate the adverse effect and maintain control of Parkinson's disease symptoms.

Official title: Adding Orally Disintegrating Selegiline (Zelapar) to Patients Taking Dopamine Agonists and Experiencing Complications

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

Reduction of adverse event:

Epworth Sleepiness Scale score for those with daytime sleepiness

Neuropsychiatric Inventory Hallucinations question and Unified Parkinson's Disease Rating Scale Part I hallucinations question for those with hallucinations

circumference of lower leg/foot at greatest point of swelling for pedal edema

Barratt Impulsiveness Scale for those with impulsive behavior

Secondary outcome:

Maintenance of efficacy:

Unified Parkinson's Disease Rating Scale Parts I-IV

PDQ-39 quality of life assessment

Beck Depression Inventory and Beck Anxiety Inventory

patient and physician global impression of change

Fatigue Severity Scale

Mini-Mental State Examination

Detailed description: Parkinson's disease (PD) is a progressive neurodegenerative disease. Symptomatic therapy is primarily aimed at restoring dopamine function in the brain. Levodopa is the most effective symptomatic treatment; however, long term use is associated with motor fluctuations (periods of return of PD symptoms when medication effect wears off) and dyskinesia (drug induced involuntary movements including chorea and dystonia). Once patients develop motor fluctuations treatment options include increasing the frequency of levodopa dosing, switching to sustained-release levodopa, adding other therapies including MAO-B inhibitors, dopamine agonists, COMT inhibitors and in patients with severe motor fluctuations deep brain stimulation surgery. There are no good evidence based studies indicating whether the use of one of these class of drugs is superior to the other nor are there treatment algorithms that recommend which class of drug should be initiated when the patients initially develop motor fluctuations. It is believed that the efficacy of the different drug classes is similar. However, the frequency of adverse effects may differ between drug classes, but such studies are lacking. In clinical practice when patients develop adverse effects to a drug from one class, a drug from another class is substituted in an attempt to maintain efficacy with reduced adverse effects.

Dopamine agonists often have a higher risk of adverse effects compared to MAO B inhibitors. Therefore, the rationale for this study is that the addition of orally disintegrating selegiline after the reduction or discontinuation of the offending dopamine agonist will result in comparable efficacy with reduced adverse events. This study will assess the safety and efficacy of the addition of orally disintegrating selegiline in PD patients who are having adverse effects to dopamine agonists for which a dose reduction of the dopamine agonist is being considered. All patients in the study will receive orally disintegrating selegiline 1. 25 mg once a day and the dose will be increased to 2. 5 mg once a day if tolerated.

Comparisons: The status of the adverse event at the end of the study while on orally disintegrating selegiline will be compared to the adverse event at the start of the study. In addition, efficacy will be compared at the start of the study while on the dopamine agonist to the end of the study with orally disintegrating selegiline.

Minimum age: 30 Years. Maximum age: 90 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Idiopathic PD confirmed by at least two of the following signs: resting tremor,

bradykinesia,rigidity

- Male or female outpatients

- Age 30-90 years

- Current use of levodopa (stable for at least 1 month) and a dopamine agonist

(pramipexole or ropinirole)

- Treatment response to current anti-parkinsonian medications in the opinion of the

investigator

- Dopamine agonist adverse effect that in the opinion of the investigator requires a

reduction or discontinuation of the dopamine agonist. The adverse effects must be in one of the following four categories and should not be so severe as to require immediate discontinuation of the dopamine agonist (i. e., hallucinations without insight, serious impulsive behavior resulting in significant loss or danger to the patient).

Daytime sleepiness - must score >10 on ESS at Baseline; Pedal edema - bothersome/concerning

to patient; Hallucinations - insight should be maintained; Impulsive behavior - not

including behaviors that are harmful to the patient requiring immediate discontinuation of the agonist.

- Daily off time

- Acceptable contraception for females of child bearing potential

- Willing and able to comply with study procedures.

- Willing and able to give written informed consent prior to beginning any study

procedures.

Exclusion Criteria:

- Atypical parkinsonism due to drugs, metabolic disorders, encephalitis, trauma, or

other neurodegenerative diseases.

- Significant cognitive or psychiatric impairment which, in the opinion of the

investigator, would interfere with the ability to complete all the tests required in the protocol.

- Participation in another clinical drug trial within the previous four weeks.

- Patients currently on MAO-A or B inhibitors, meperidine, tramadol, methadone,

propoxyphene, dextromethorphan, and mirtazapine.

- History of hypersensitivity or adverse reaction to selegiline or previous exposure to

orally disintegrating selegiline

- History of melanoma

- Unstable/uncontrolled medical problems

- History of drug/alcohol abuse

Coastal Neurological Medical Group, Inc, La Jolla, California 92037, United States; Recruiting
Kelly Vandever, Phone: 858-453-3842, Ext: 15, Email: kelly_coastal@hotmail.com
Dee Silver, MD, Principal Investigator

University of California - Irvine, Irvine, California 92697, United States; Completed

University of Southern California, Los Angeles, California 90093, United States; Completed

The Parkinson's Institute, Sunnyvale, California 94085, United States; Completed

Parkinson's Disease and Movement Disorder Center of Boca Raton, Boca Raton, Florida 33486, United States; Completed

University of South Florida, Tampa, Florida 33606, United States; Recruiting
Summer Wolfrath, Phone: 813-844-4399, Email: swolfrat@health.usf.edu
Robert Hauser, MD, Principal Investigator

Methodist Plaza Speciality Clinic, Des Moines, Iowa 50309, United States; Completed

University of Kansas Medical Center, Kansas City, Kansas 66160, United States; Completed

Ochsner Clinic Foundation, New Orleans, Louisiana 70121, United States; Completed

Harvard Vanguard Medical Associates, Boston, Massachusetts 02215, United States; Completed

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States; Completed

Henry Ford Health Center - Franklin Pointe, Southfield, Michigan 48034, United States; Completed

Struthers Parkinson's Center, Golden Valley, Minnesota 55427, United States; Completed

University of Toledo, Toledo, Ohio 43614, United States; Completed

NeuroHealth Parkinson Disease and Movement Disorder Center, Warwick, Rhode Island 02886, United States; Completed

Neurology Specialists Dallas, Dallas, Texas 75231, United States; Completed

ETMC Neurological Institute, Tyler, Texas 75701, United States; Completed

Starting date: March 2007
Ending date: September 2008
Last updated: August 29, 2008