Phase I Deep Brain Stimulation (DBS) vs. Best Medical Therapy (BMT) Trial

Study Overview
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Brief Summary
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The goals of this study are to determine if simultaneous bilateral subthalamic nucleus stimulation or simultaneous bilateral globus pallidus stimulation is more effective in reducing symptoms of Parkinson's disease, and if deep brain stimulation or best medical therapy is more effective in improving Parkinson's disease symptoms

Detailed Description
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Deep Brain Stimulation (DBS) is a promising therapy for Parkinson's disease (PD). Whether DBS is superior to comprehensive best medical therapy or whether some patients or symptoms respond better to DBS in one area of the brain or the other is currently not known. The goals of this project are to compare the effectiveness of DBS and comprehensive medical therapy as treatments for PD, and to compare bilateral DBS at 2 areas of the brain--the subthalamic nucleus (STN) and the globus pallidus (Gpi)--to determine the most effective brain site for surgical intervention In this prospective, randomized, multi-center trial, 316 patients will be enrolled at 13 centers over four and a half years. Patients will initially be randomized to immediate surgery (DBS) or to 6 months of best medical therapy. BMT patients will then proceed into the surgical phase of the trial. The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial. Patients will be followed for two years post surgery (24-30 months). Effective 08/05/05, randomization to the BMT arm has been discontinued since the study has sufficient information to compare the outcomes of DBS and BMT patients at 6 months. The findings will be critically important in establishing the optimal surgical treatment of the disabling symptoms of PD.

Official Title
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CSP #468 Phase I - A Comparison of Best Medical Therapy and Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus for the Treatment of Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Device: Bilateral Deep Brain Stimulation
* Other: best medical therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: idiopathic Parkinson's disease, Hoehn and Yahr stage 2 or worse off medications, L-dopa responsive but with persistent disabling symptoms (i.e., refractory to best medical treatment with motor fluctuations, dyskinesias), on stable medical therapy for at least one month prior to enrollment, age > 21, available and willing to be followed-up according to study protocol, and no intracranial abnormalities that would contraindicate surgery (based on pre-operative magnetic resonance imaging of the brain). Exclusion Criteria: Parkinson's plus syndromes, medical contraindications to surgery or stimulation, active alcohol or drug abuse, score on minimental status exam 24 or lower, or other neuropsychological dysfunction (e.g., dementia) that would contraindicate surgery, concurrent participation in another research protocol.

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Deep Brain Stimulation | Device: Bilateral Deep Brain Stimulation<br>* The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.<br>|
| Active Comparator: 2<br>Best Medical Therapy | Other: best medical therapy<br>* Participants will initially be randomized to DBS or to 6 months of best medical therapy. BMT participants will then proceed into the surgical phase of the trial. Effective 08/05/05, randomization to the BMT arm has been discontinued since the study has sufficient information to compare the outcomes of DBS and BMT patients at 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Difference of Time Spent in the 'on' State Without Troublesome Dyskinesia Based on Patient Motor Diaries as Compared to the Baseline. |  | at six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change of Scores on the UPDRS for Blinded Assessed Motor Function 'Off' Medication and 'on' Stimulation | Unified Parkinson's Disease Rating Scale (UPDRS Part III) measured while the patient is off medications and on stimulation at follow-up visits post surgery. UPDRS Part III has 14 items assessing motor skills including facial expression and speech, tremors, rigidity, posture, gait, and bradykinesia. Left and right sides (arms, legs, and hands) are assessed separately for seven of the functions. A summary score ranging from 0 to 108 is generated by adding the 14 specific motor function responses. The motor function (UPDRS part III) assessments are done by turning on the stimulation with and without taking PD medications (on/off) at each in-person visit. The higher score indicates that the condition is worse. | at six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, levo-dopa, tremor, dyskinesia, subthalamic nucleus, globus pallidus