Clinical trial NCT01076452: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
levo-dopa
tremor
dyskinesia
subthalamic nucleus
globus pallidus
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Medtronic
First posted: 2010-02-26
Enrollment: 299
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The Change From Baseline in the UPDRS-III Score at 24 Months With Deep-brain Stimulation and Without Medication.
timeFrame: Baseline and 24 months
Secondary outcomes:
measure: The Change From Baseline in the UPDRS Scores Part I (Mentation) at 24 Months.
timeFrame: Baseline and 24 months
measure: The Change From Baseline in the UPDRS Scores Part II (Activity of Daily Living) at 24 Months.
timeFrame: Baseline and 24 months
measure: The Change From Baseline in the UPDRS Scores Part IV (Complication of Therapy) at 24 Months.
timeFrame: Baseline and 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: San Francisco
country: United States
facility: VA Medical Center, San Francisco
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West LA
state: California
city: Iowa City
country: United States
facility: VA Medical Center, Iowa City
state: Iowa
city: Portland
country: United States
facility: VA Medical Center, Portland
state: Oregon
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia, OPC
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center (152)
state: Texas
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
city: Richmond
country: United States
facility: Medical College of Virginia
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound Health Care System, Seattle
state: Washington
Study officials:
affiliation: VA Medical Center, Iowa City
name: Kenneth Follett
role: STUDY_CHAIR
References:
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.
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.
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.
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.
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.