Adding Orally Disintegrating Selegiline (Zelapar) to Patients Taking Dopamine Agonists and Experiencing Complications
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 77
- 试验地点
- 17
- 主要终点
- Percentage of Participants With Reduction in Adverse Events
研究概览
简要总结
The purpose of the study is to determine if reducing or eliminating a dopamine agonist (DA) 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 (PD) symptoms.
详细描述
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 monoamine oxidase type B (MAO-B) inhibitors, dopamine agonists, catechol-o-methyltransferase (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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Idiopathic Parkinson's disease (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 Epworth Sleepiness Scale (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.
排除标准
- •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 monoamine oxidase type A or B (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
研究组 & 干预措施
orally disintegrating selegiline
This is a one arm open label study of patients who are experiencing a dopamine agonist (DA) related adverse effects (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder. All subjects received orally disintegrating selegiline.
干预措施: orally disintegrating selegiline (Zelapar) (Drug)
结局指标
主要结局
Percentage of Participants With Reduction in Adverse Events
时间窗: 3 Months
The primary outcome measure was the reduction of daytime sleepiness, hallucinations, pedal edema, and impulse control disorders after a reduction of dopamine agonist dose with the addition of an monoamine oxidase (MAO)-B inhibitor (orally disintegrating selegiline). Percentages of participants with reduction in individual adverse events as well as reduction in any adverse events are reported.
Neuropsychiatric Inventory (NPI) Hallucinations Scale Score for Those With Hallucinations
时间窗: Baseline and 3 months
Report of hallucinations with insight maintained based on the hallucinations questions of the Neuropsychiatric Inventory (NPI). The participant and their caregiver are asked a series of questions to determine if hallucinations are present. If present they rate the frequency of hallucinations on a scale of 1 (rarely, less than once a week) to 4, very often (once or more daily). They also rate the severity of the hallucinations, as mild (1 - present but harmless and cause little distress), moderate (2 - distressing and disruptive) or severe (3 - very disruptive, major source of behavioral disturbance, may need meds). The frequency and severity scores are multiplied (maximum score 12, with higher scores representing more distress/disability) for the total score.
Epworth Sleepiness Scale Score for Those With Daytime Sleepiness
时间窗: Baseline and 3 months
This is a measure of daytime sleepiness. The test is a list of eight situations in which one rates their tendency to become sleepy on a scale of 0, no change of dozing to 3, high chance of dozing. The total score ranges fro 0-24, with higher values representing excessive sleepiness. A score of greater than 10 represents clinically significant sleepiness.
Circumference of Lower Leg/Foot at Greatest Point of Swelling for Pedal Edema
时间窗: Baseline and 3 months
The circumference of the lower leg/ankle with the greatest swelling was measured using a standard tape measure at baseline and 12 weeks for both the right and left ankles.
Barratt Impulsiveness Scale Score for Those With Impulsive Behavior
时间窗: Baseline and 3 months
This is a measure of impulsiveness. There are 30 questions regarding the presence of impulsive and non-impulsive behaviors each scored from 1 (rarely/never) to 4 (almost always/always). The total score reflects the sum of the 30 items. A higher score represents more impulsiveness.
次要结局
- Unified Parkinson's Disease Rating Scale (UPDRS) Scores(Baseline and 3 months)
- Beck Depression Inventory for All Subjects(Baseline and 3 months)
- Mini Mental State Examination (MMSE) Scores for All Subjects(Baseline and 3 months)
- PDQ-39 Quality of Life Assessment Total Scores(Baseline and 3 months)
- Beck Anxiety Inventory Scores for All Subjects(Baseline and 3 months)
研究者
Stuart Isaacson
MD, Director of the Parkinson's Disease and Movement Disorder Center of Boca Raton
Parkinson's Disease and Movement Disorder Center of Boca Raton