The goals of this project are to compare the effectiveness of Deep Brain Stimulation (DBS) and comprehensive medical therapy as treatments for Parkinson's Disease (PD), and to compare bilateral DBS at 2 areas of the brain to determine the most effective brain site for surgical intervention. Patients will be randomized to immediate surgery (DBS) or to 6 months of "best medical therapy" (BMT). Outcomes of DBS and BMT patients will be compared at 6 months. BMT patients will then proceed into the surgical phase of the trial. The DBS site will be assigned on a random basis at the time the patient enters the surgical phase of the trial. Patients will be followed for a minimum of 2 years and a maximum of 3 years following surgery depending upon when they were enrolled. The findings will be critically important in establishing the optimal surgical treatment of the disabling symptoms of PD.

Condition	Treatment or Intervention	Phase
Idiopathic Parkinson's Disease	Device: Deep Brain Stimulation  Procedure: Comprenhensive Medical Therapy	Phase III

Further Study Details: 

Expected Total Enrollment:  316

Primary Objectives: There are two components to this study, a comparison of best medical therapy (BMT) to deep brain stimulation (DBS) and a comparison of globus pallidus (GPi) to subthalamic nucleus (STN) DBS on patient outcomes. Our first primary objective (assessed at two years post surgery) is to determine whether simultaneous bilateral STN stimulation or simultaneous bilateral GPi stimulation is more effective in attenuating symptoms of Parkinson's Disease at two years.

Secondary Objective: To determine whether deep brain stimulation (DBS) or best medical therapy (BMT) is more effective at six months in improving PD motor symptoms.

Intervention: The surgical intervention consists of bilateral STN and GPi deep brain stimulation (DBS) and the comparison arm consists of best medical therapy followed six months later with deep brain stimulation. In the surgery study arm, STN stimulation is the experimental arm and GPi stimulation is the comparison arm.

Primary Outcomes: The primary study endpoint for comparison of surgical site (STN vs. GPi DBS) is the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS). For the comparison of BMT to DBS, the primary endpoint will be time spent in the 'on' state without troubling dyskinesias, based on patient motor diaries.

Study Abstract: Parkinson’s Disease (PD), which is characterized by the clinical triad of akinesia, rigidity, and tremor, can result in significant disability and morbidity. With a prevalence rate of approximately 150 per 100,000 population, the disease affects approximately three-quarters to one million people in the United States. A survey of the inpatient census of the Department of Veterans Affairs medical centers over a five year period identified over 41,000 veterans with a primary (12%) or secondary diagnosis (88%) of PD. These numbers do not take into account veterans with PD who are treated on an outpatient basis, which is expected to be significantly larger than the number who are admitted to an inpatient unit. PD patients may have persistent disabling symptoms even when treated with the best medication regimens available, or they may suffer intolerable medication side effects that limit effective treatment of the disease. Many of these individuals who have symptoms that are refractory to medical management may be candidates for surgical therapy. In the early 1990s, pallidotomy (making a small lesion in a portion of the brain called the globus pallidus) became the standard surgical treatment for PD. Unilateral pallidotomy is generally safe but bilateral pallidotomy, which would be required to treat the bilateral symptoms of PD, is considered by many movement disorders specialists to have an unacceptably high risk of complication. This limitation of pallidotomy has driven intense interest in finding a non-ablative surgical alternative. Deep brain stimulation (DBS), a non-destructive treatment that could be used bilaterally, has emerged as the preferred surgical treatment for PD. A growing number of studies indicate that DBS of the globus pallidus or subthalamic nucleus ameliorates many symptoms of PD but it is not known whether the clinical benefit is superior to that achieved with comprehensive medical therapy, whether the clinical benefit is maintained, or which brain structure (i.e., globus pallidus or subthalamic nucleus) is the best site for stimulation. This study will evaluate the efficacy of DBS compared to best medical therapy and will compare the effectiveness of bilateral DBS of the globus pallidus to bilateral DBS of the subthalamic nuclei in attenuating symptoms of PD.

This will be a prospective, randomized, multi-center trial. Three hundred sixteen patients will be enrolled at 13 centers over two years. Patients will be followed for two years post surgery (24-30 months). All treatments related to the study will be provided at the 6 VA PADRECC centers and their affiliated academic medical centers (approximately 26 patients/center). Upon enrollment in the study, patients will be randomized to either "best medical therapy" (BMT) or surgery (STN or GPi DBS). Those patients randomized to BMT will be treated for 6 months, at which time they will be randomly assigned to one of the surgical interventions. All patients (immediate or delayed surgery) will be randomized to either STN or GPi DBS.

Key study inclusion criteria include: idiopathic Parkinson’s disease, L-dopa responsive with clearly defined 'on' periods, persistent disabling symptoms (e.g., motor fluctuations with disabling "off" periods) despite medical therapy, stable on 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. Exclusions include "Parkinson’s plus" syndromes, medical contraindications to surgery, stimulation, or magnetic resonance imaging, and active alcohol or drug abuse. The primary study endpoint at six months will be time spent in the "on" state without troubling dyskinesias. At two years, the primary study endpoint will be scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) for motor function "off" medication and "on" stimulation. Secondary outcomes will include UPDRS scores for activities of daily living and dyskinesias, the Schwab and England score, Hoehn and Yahr score, the Parkinson’s Disease Questionnaire-39 (a disease-specific health-related quality of life measure), the SF-36 generic quality of life instrument, the quality of well being scale, health resource use, therapy complications, neuropsychological assessment, and medication use. Subjects will be stratified based on age and study site.

DBS is a promising therapy for PD. Whether DBS is superior to comprehensive (best) medical therapy, whether the effectiveness of DBS differs by site or whether some patients or symptoms respond better to stimulation in one site or the other is not known. The goals of this project are to study the efficacy of DBS and to compare two sites of bilateral DBS to determine the most effective site for surgical intervention. The findings will be critically important in establishing the optimal surgical treatment of the disabling symptoms of Parkinson’s Disease.

Ages Eligible for Study:  22 Years and above,  Genders Eligible for Study:  Both

Criteria

• Patients with Parkinson's disease who have persistent disabling symptoms despite optimal medical therapy are suitable for this study.
• Patients who are qualified will receive the most advanced deep brain stimulator device (Kinetra by Medtronic,Inc.).

California
      San Francisco VA Medical Center, San Francisco,  California,  94121,  United States; Recruiting
      West LA VA Medical Center, West Los Angeles,  California,  90073,  United States; Recruiting
      University of California at San Francisco/UCSF, San Francisco,  California,  94143,  United States; Recruiting
      Univ. of California at Los Angeles, Los Angeles,  California,  90095,  United States; Recruiting
Florida
      University of South Florida, Tampa,  Florida,  33606,  United States; Not yet recruiting
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160,  United States; Terminated
Oregon
      Portland VA Medical Center, Portland,  Oregon,  97201,  United States; Recruiting
      Oregon Health and Science University/OHSU, Portland,  Oregon,  97201,  United States; Recruiting
Pennsylvania
      Philadelphia VA Medical Center, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
      Univ. of Pennsylvania Health System/UPHS, Philadelphia,  Pennsylvania,  19107,  United States; Recruiting
Texas
      Houston VA Medical Center, Houston,  Texas,  77030-2498,  United States; Recruiting
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
Virginia
      Richmond VA Medical Center, Richmond,  Virginia,  23249,  United States; Recruiting
      Medical College of Virginia, Richmond,  Virginia,  23298,  United States; Recruiting
Washington
      Puget Sound Health Care System/PADRECC, Seattle,  Washington,  98108,  United States; Recruiting

Study ID Numbers:  468
Record last reviewed:  January 2005
Last Updated:  January 13, 2005
Record first received:  January 10, 2005
ClinicalTrials.gov Identifier:  NCT00101556
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08