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

Primary Purpose

Parkinson's Disease

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Bilateral Deep Brain Stimulation
Sponsored by
US Department of Veterans Affairs
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's Disease, levo-dopa, tremor, dyskinesia, subthalamic nucleus, globus pallidus

Eligibility Criteria

22 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California at Los Angeles
  • University of California at San Francisco
  • VA Medical Center, San Francisco
  • VA Greater Los Angeles Healthcare System, West LA
  • VA Medical Center, Iowa City
  • VA Medical Center, Portland
  • Oregon Health Sciences University
  • University of Pennsylvania Hospital
  • Philadelphia, OPC
  • Baylor College of Medicine
  • Michael E. DeBakey VA Medical Center (152)
  • Hunter Holmes McGuire VA Medical Center
  • Medical College of Virginia
  • VA Puget Sound Health Care System, Seattle

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

STN

GPi

Arm Description

Participants were randomized to receive deep brain stimulation on STN (Subthalamic Nucleus) target.

Participants were randomized to receive deep brain stimulation on GPi (Globus Pallidus) target.

Outcomes

Primary Outcome Measures

The Change From Baseline in the UPDRS-III Score at 24 Months With Deep-brain Stimulation and Without Medication.
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.
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.
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.
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.

Full Information

First Posted
February 24, 2010
Last Updated
June 27, 2014
Sponsor
US Department of Veterans Affairs
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Medtronic
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1. Study Identification

Unique Protocol Identification Number
NCT01076452
Brief Title
Phase II Subthalamic Nucleus (STN) vs. Globus Pallidus (GPi) Trial
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
April 2002 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
US Department of Veterans Affairs
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Medtronic

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's Disease, levo-dopa, tremor, dyskinesia, subthalamic nucleus, globus pallidus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
299 (Actual)

8. Arms, Groups, and Interventions

Arm Title
STN
Arm Type
Active Comparator
Arm Description
Participants were randomized to receive deep brain stimulation on STN (Subthalamic Nucleus) target.
Arm Title
GPi
Arm Type
Active Comparator
Arm Description
Participants were randomized to receive deep brain stimulation on GPi (Globus Pallidus) target.
Intervention Type
Device
Intervention Name(s)
Bilateral Deep Brain Stimulation
Intervention Description
The DBS site (STN or GPi) was assigned on a random basis at the time the patient enters the surgical phase of the trial.
Primary Outcome Measure Information:
Title
The Change From Baseline in the UPDRS-III Score at 24 Months With Deep-brain Stimulation and Without Medication.
Description
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.
Time Frame
Baseline and 24 months
Secondary Outcome Measure Information:
Title
The Change From Baseline in the UPDRS Scores Part I (Mentation) at 24 Months.
Description
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.
Time Frame
Baseline and 24 months
Title
The Change From Baseline in the UPDRS Scores Part II (Activity of Daily Living) at 24 Months.
Description
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.
Time Frame
Baseline and 24 months
Title
The Change From Baseline in the UPDRS Scores Part IV (Complication of Therapy) at 24 Months.
Description
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.
Time Frame
Baseline and 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenneth Follett
Organizational Affiliation
VA Medical Center, Iowa City
Official's Role
Study Chair
Facility Information:
Facility Name
University of California at Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
Facility Name
University of California at San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94121
Country
United States
Facility Name
VA Medical Center, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94121
Country
United States
Facility Name
VA Greater Los Angeles Healthcare System, West LA
City
West Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
Facility Name
VA Medical Center, Iowa City
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52246-2208
Country
United States
Facility Name
VA Medical Center, Portland
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201
Country
United States
Facility Name
Oregon Health Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97207
Country
United States
Facility Name
University of Pennsylvania Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Philadelphia, OPC
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19106
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Michael E. DeBakey VA Medical Center (152)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hunter Holmes McGuire VA Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
Medical College of Virginia
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
VA Puget Sound Health Care System, Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19126811
Citation
Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, Rothlind J, Sagher O, Reda D, Moy CS, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein J, Stoner G, Heemskerk J, Huang GD; CSP 468 Study Group. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009 Jan 7;301(1):63-73. doi: 10.1001/jama.2008.929.
Results Reference
result
PubMed Identifier
20519680
Citation
Follett KA, Weaver FM, Stern M, Hur K, Harris CL, Luo P, Marks WJ Jr, Rothlind J, Sagher O, Moy C, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein JM, Stoner G, Starr PA, Simpson R, Baltuch G, De Salles A, Huang GD, Reda DJ; CSP 468 Study Group. Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease. N Engl J Med. 2010 Jun 3;362(22):2077-91. doi: 10.1056/NEJMoa0907083.
Results Reference
result
PubMed Identifier
22722632
Citation
Weaver FM, Follett KA, Stern M, Luo P, Harris CL, Hur K, Marks WJ Jr, Rothlind J, Sagher O, Moy C, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein JM, Stoner G, Starr PA, Simpson R, Baltuch G, De Salles A, Huang GD, Reda DJ; CSP 468 Study Group. Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes. Neurology. 2012 Jul 3;79(1):55-65. doi: 10.1212/WNL.0b013e31825dcdc1. Epub 2012 Jun 20.
Results Reference
result
PubMed Identifier
23667214
Citation
Weintraub D, Duda JE, Carlson K, Luo P, Sagher O, Stern M, Follett KA, Reda D, Weaver FM; CSP 468 Study Group. Suicide ideation and behaviours after STN and GPi DBS surgery for Parkinson's disease: results from a randomised, controlled trial. J Neurol Neurosurg Psychiatry. 2013 Oct;84(10):1113-8. doi: 10.1136/jnnp-2012-304396. Epub 2013 May 10.
Results Reference
result
PubMed Identifier
25185211
Citation
Rothlind JC, York MK, Carlson K, Luo P, Marks WJ Jr, Weaver FM, Stern M, Follett K, Reda D; CSP-468 Study Group. Neuropsychological changes following deep brain stimulation surgery for Parkinson's disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy. J Neurol Neurosurg Psychiatry. 2015 Jun;86(6):622-9. doi: 10.1136/jnnp-2014-308119. Epub 2014 Sep 2.
Results Reference
derived

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

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