Phase II Subthalamic Nucleus (STN) vs. Globus Pallidus (GPi) Trial

This study has been completed.
Sponsor:
Collaborators:
Medtronic
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01076452
First received: February 24, 2010
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

The goal of the second phase of the study is to determine if simultaneous bilateral subthalamic nucleus stimulation or simultaneous bilateral globus pallidus stimulation is more effective in reducing symptoms of Parkinson's Disease.


Condition Intervention Phase
Parkinson's Disease
Device: Bilateral Deep Brain Stimulation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: CSP #468 Phase II - A Comparison of Best Medical Therapy and Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus for the Treatment of Parkinson's Disease, Phase II

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • The Change From Baseline in the UPDRS-III Score at 24 Months With Deep-brain Stimulation and Without Medication. [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    The primary outcome measure for the comparison of GPi deep brain stimulation (DBS) to STN DBS is the motor function score of the 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. 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. A summary score ranging from 0 to 108 is generated by adding the 14 specific motor function responses. The higher score indicates the worse motor function.


Secondary Outcome Measures:
  • The Change From Baseline in the UPDRS Scores Part I (Mentation) at 24 Months. [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    The UPDRS has four parts (Parts I-IV) in which a total of 42 disease characteristics are assessed. Most characteristics are assessed according to their severity on a 0-4 scale (0 = normal, 4 = most substantial impairment), and some are assessed only for absence (score = 0) or presence (score = 1). Part I has four items assessing intellectual impairment, thought disorder, depression and motivation. A summary score ranging from 0 to16 is generated by adding the four items. The higher score indicates worse condition.

  • The Change From Baseline in the UPDRS Scores Part II (Activity of Daily Living) at 24 Months. [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    The UPDRS has four parts (Parts I-IV) in which a total of 42 disease characteristics are assessed. Most characteristics are assessed according to their severity on a 0-4 scale (0 = normal, 4 = most substantial impairment), and some are assessed only for absence (score = 0) or presence (score = 1). Part II has 13 items focusing on activities of daily living including walking, writing, dressing and speech. A summary score ranging from 0 to 52 is generated by adding the 13 items. The higher score indicates worse condition.

  • The Change From Baseline in the UPDRS Scores Part IV (Complication of Therapy) at 24 Months. [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    The UPDRS has four parts (Parts I-IV) in which a total of 42 disease characteristics are assessed. Most characteristics are assessed according to their severity on a 0-4 scale (0 = normal, 4 = most substantial impairment), and some are assessed only for absence (score = 0) or presence (score = 1). Part IV includes four categories (11 items) related to dyskinesias, clinical fluctuations of symptoms, and other complications. A summary score ranging from 0 to 23 is generated by adding the four items. The higher score indicates worse condition.


Enrollment: 299
Study Start Date: April 2002
Study Completion Date: April 2009
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: STN
Participants were randomized to receive deep brain stimulation on STN (Subthalamic Nucleus) target.
Device: Bilateral Deep Brain Stimulation
The DBS site (STN or GPi) was assigned on a random basis at the time the patient enters the surgical phase of the trial.
Active Comparator: GPi
Participants were randomized to receive deep brain stimulation on GPi (Globus Pallidus) target.
Device: Bilateral Deep Brain Stimulation
The DBS site (STN or GPi) was assigned on a random basis at the time the patient enters the surgical phase of the trial.

Detailed Description:

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 (Phase I) 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 (Phase II) 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 arm patients will then be randomized to proceed into the DBS surgical phase of the trial. The DBS site (STN pr 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 months for DBS only patients and 30 months for BMT-DBS patients) Effective 8/5/05 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.

  Eligibility

Ages Eligible for Study:   22 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • idiopathic Parkinson's Disease
  • Hoehn and Yahr stage 2 or worse when off medications
  • L-dopa responsive with clearly defined "on" periods (i.e. symptoms improve at least partially with L-dopa administration, a characteristic that helps distinguish idiopathic PD from "Parkinson's Plus" and atypical Parkinson's syndromes-see below)
  • persistent disabling symptoms (e.g. on troubling dyskinesias, or disabling "off" periods at least 3 hours/day) despite medication therapy. Patients will have been treated with variable doses of levodopa and dopamine agonists (at a minimum) and will have had an adequate trial of other adjunctive medications)
  • stable on medical therapy for at least one month prior to study enrollment
  • age >21
  • available and willing to be followed-up according to study protocol

Exclusion Criteria:

  • "Parkinson's plus" syndromes, secondary, or atypical Parkinson's syndromes (e.g. progressive supranuclear palsy, striato-nigral degeneration, multiple system atrophy, post-stroke, post-traumatic, or post-encephalitic Parkinson's. These patients have cardinal symptoms characteristic of PD but with additional symptoms indicating other organic brain dysfunction, such as gaze palsies, autonomic dysfunction, lack of response to L-dopa, these individuals tend not to improve with standard treatments for PD)
  • previous Parkinson's Disease surgery
  • medical contraindications to surgery or stimulation (e.g. uncontrolled hypertension, advanced coronary artery disease, other implanted stimulation or electronically-controlled devices including cardiac demand pacemaker, aneurysm clips, cochlear implants, or a spinal cord stimulator) (Note: for the subject who receives either a pacemaker and/or defibrillator after this study enrollment, he/she will be allowed to continue the study if the neurostimulator system can be adequately programmed to permit system compatibility)
  • contraindication to magnetic resonance imaging (e.g. indwelling metal fragments or implants that might be affected by MRI)
  • active alcohol or drug abuse
  • score on Mini-Mental Status examination of 24 or lower, or other neuropsychological dysfunction 9e.g. dementia) that would contraindicate surgery
  • intracranial abnormalities that would contraindicate surgery (e.g. stroke, tumor, vascular abnormality affecting the target area)
  • pregnancy
  • concurrent participation in another research protocol
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01076452

Locations
United States, California
University of California at Los Angeles
Los Angeles, California, United States, 90073
VA Medical Center, San Francisco
San Francisco, California, United States, 94121
University of California at San Francisco
San Francisco, California, United States, 94121
VA Greater Los Angeles Healthcare System, West LA
West Los Angeles, California, United States, 90073
United States, Iowa
VA Medical Center, Iowa City
Iowa City, Iowa, United States, 52246-2208
United States, Oregon
VA Medical Center, Portland
Portland, Oregon, United States, 97201
Oregon Health Sciences University
Portland, Oregon, United States, 97207
United States, Pennsylvania
Philadelphia, OPC
Philadelphia, Pennsylvania, United States, 19106
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Michael E. DeBakey VA Medical Center (152)
Houston, Texas, United States, 77030
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Virginia
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, United States, 23249
Medical College of Virginia
Richmond, Virginia, United States, 23249
United States, Washington
VA Puget Sound Health Care System, Seattle
Seattle, Washington, United States, 98108
Sponsors and Collaborators
Medtronic
Investigators
Study Chair: Kenneth Follett VA Medical Center, Iowa City
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01076452     History of Changes
Other Study ID Numbers: 468 Phase II, VA-NINDS-01
Study First Received: February 24, 2010
Results First Received: September 11, 2013
Last Updated: November 26, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Parkinson's Disease
levo-dopa
tremor
dyskinesia
subthalamic nucleus
globus pallidus

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on April 23, 2014