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

NCT ID: NCT01076452

Last Updated: 2014-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 299 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-04-30
• Study Completion Date: 2009-04-30

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

STN

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

Group Type: ACTIVE_COMPARATOR

Bilateral Deep Brain Stimulation

Intervention Type: DEVICE

The DBS site (STN or GPi) was assigned on a random basis at the time the patient enters the surgical phase of the trial.

GPi

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

Group Type: ACTIVE_COMPARATOR

Bilateral Deep Brain Stimulation

Intervention Type: DEVICE

The DBS site (STN or GPi) was assigned on a random basis at the time the patient enters the surgical phase of the trial.

Interventions

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.

Intervention Type: DEVICE

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

• Minimum Eligible Age: 22 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Medtronic

INDUSTRY

Sponsor Role: collaborator

US Department of Veterans Affairs

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kenneth Follett

Role: STUDY_CHAIR

VA Medical Center, Iowa City

Locations

University of California at Los Angeles

Los Angeles, California, United States

University of California at San Francisco

San Francisco, California, United States

VA Medical Center, San Francisco

San Francisco, California, United States

VA Greater Los Angeles Healthcare System, West LA

West Los Angeles, California, United States

VA Medical Center, Iowa City

Iowa City, Iowa, United States

VA Medical Center, Portland

Portland, Oregon, United States

Oregon Health Sciences University

Portland, Oregon, United States

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Philadelphia, OPC

Philadelphia, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, United States

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, United States

Medical College of Virginia

Richmond, Virginia, United States

VA Puget Sound Health Care System, Seattle

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 19126811 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20519680 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22722632 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23667214 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25185211 (View on PubMed)

Other Identifiers

VA-NINDS-01

Identifier Type: OTHER

Identifier Source: secondary_id

468 Phase II

Identifier Type: -

Identifier Source: org_study_id