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

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ClinicalTrials.gov Identifier: NCT01076452
Recruitment Status : Completed
First Posted : February 26, 2010
Results First Posted : January 15, 2014
Last Update Posted : July 14, 2014
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Medtronic
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Tracking Information
First Submitted Date  ICMJE February 24, 2010
First Posted Date  ICMJE February 26, 2010
Results First Submitted Date  ICMJE September 11, 2013
Results First Posted Date  ICMJE January 15, 2014
Last Update Posted Date July 14, 2014
Study Start Date  ICMJE April 2002
Actual Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2013)
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 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 25, 2010)
Blinded assessment of motor function (Unified Parkinson's Disease Rating Scale (UPDRS) Part III) scores in the on stimulation/off medication condition [ Time Frame: at two years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2013)
  • The Change From Baseline in the UPDRS Scores Part I (Mentation) at 24 Months. [ Time Frame: Baseline and 24 months ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2010)
  • Self-reported function [ Time Frame: at two years ]
  • UPDRS scores [ Time Frame: at two years ]
  • Quality of life [ Time Frame: at two years ]
  • Neurocognitive function [ Time Frame: at two years ]
  • Adverse events [ Time Frame: at two years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Subthalamic Nucleus (STN) vs. Globus Pallidus (GPi) Trial
Official Title  ICMJE 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
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Parkinson's Disease
Intervention  ICMJE 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.
Study Arms  ICMJE
  • Active Comparator: STN
    Participants were randomized to receive deep brain stimulation on STN (Subthalamic Nucleus) target.
    Intervention: Device: Bilateral Deep Brain Stimulation
  • Active Comparator: GPi
    Participants were randomized to receive deep brain stimulation on GPi (Globus Pallidus) target.
    Intervention: Device: Bilateral Deep Brain Stimulation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 7, 2013)
299
Original Actual Enrollment  ICMJE
 (submitted: February 25, 2010)
316
Actual Study Completion Date  ICMJE April 2009
Actual Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 22 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01076452
Other Study ID Numbers  ICMJE 468 Phase II
VA-NINDS-01 ( Other Identifier: NIH-NINDS )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party VA Office of Research and Development ( US Department of Veterans Affairs )
Study Sponsor  ICMJE US Department of Veterans Affairs
Collaborators  ICMJE
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Medtronic
Investigators  ICMJE
Study Chair: Kenneth Follett VA Medical Center, Iowa City
PRS Account VA Office of Research and Development
Verification Date June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP