Phase I Deep Brain Stimulation (DBS) vs. Best Medical Therapy (BMT) Trial

NCT00056563 | Completed Phase 3 Results DMC

• 1 other identifier: 468 Phase I
• Study Type: interventional
• Target: 255
• Locations: 1 country
• Sites: 14

Brief Summary

The goals of this study are to determine if simultaneous bilateral subthalamic nucleus stimulation or simultaneous bilateral globus pallidus stimulation is more effective in reducing symptoms of Parkinson's disease, and if deep brain stimulation or best medical therapy is more effective in improving Parkinson's disease symptoms

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; levo-dopa; tremor; dyskinesia; subthalamic nucleus; globus pallidus

Outcome Measures

Primary Outcomes (1)

• The Difference of Time Spent in the 'on' State Without Troublesome Dyskinesia Based on Patient Motor Diaries as Compared to the Baseline.

  at six months

Secondary Outcomes (1)

• The Change of Scores on the UPDRS for Blinded Assessed Motor Function 'Off' Medication and 'on' Stimulation

  at six months

Study Arms (2)

1

ACTIVE COMPARATOR

Deep Brain Stimulation

Device: Bilateral Deep Brain Stimulation

2

ACTIVE COMPARATOR

Best Medical Therapy

Other: best medical therapy

Interventions

Bilateral Deep Brain Stimulation DEVICE

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

1

best medical therapy OTHER

Participants will initially be randomized to DBS or to 6 months of "best medical therapy." BMT participants will then proceed into the surgical phase of the trial. Effective 08/05/05, 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.

2

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• idiopathic Parkinson's disease,
• Hoehn and Yahr stage 2 or worse "off" medications,
• L-dopa responsive but with persistent disabling symptoms (i.e., refractory to "best medical treatment" with motor fluctuations, dyskinesias),
• on stable medical therapy for at least one month prior to enrollment,
• age \> 21,
• available and willing to be followed-up according to study protocol, and
• no intracranial abnormalities that would contraindicate surgery (based on pre-operative magnetic resonance imaging of the brain).

You may not qualify if:

• "Parkinson's plus" syndromes,
• medical contraindications to surgery or stimulation,
• active alcohol or drug abuse,
• score on minimental status exam 24 or lower, or other neuropsychological dysfunction (e.g., dementia) that would contraindicate surgery,
• concurrent participation in another research protocol.

Sponsors & Collaborators

• US Department of Veterans Affairs: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (14)

University of California at Los Angeles

Los Angeles, California, 90095, United States

Location

VA Medical Center, San Francisco

San Francisco, California, 94121, United States

Location

University of California at San Francisco

San Francisco, California, 94143, United States

Location

VA Greater Los Angeles Healthcare System, West LA

West Los Angeles, California, 90073, United States

Location

VA Medical Center, Iowa City

Iowa City, Iowa, 52246-2208, United States

Location

VA Medical Center, Portland

Portland, Oregon, 97201, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

VA Medical Center, Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, 77030, United States

Location

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Medical College of Virginia

Richmond, Virginia, 23298, United States

Location

VA Puget Sound Health Care System, Seattle

Seattle, Washington, 98108, United States

Location

Related Publications (11)

• Follett K, Weaver F, Stern M, Marks W, Hogarth P, Holloway K, Bronstein J, Duda J, Horn S, Lai E, Samii A. Multisite randomized trial of deep brain stimulation. Arch Neurol. 2005 Oct;62(10):1643-4; author reply 1644-5. doi: 10.1001/archneur.62.10.1643-b. No abstract available.

  PMID: 16216957 RESULT

• Weaver F, Follett K, Hur K, Ippolito D, Stern M. Deep brain stimulation in Parkinson disease: a metaanalysis of patient outcomes. J Neurosurg. 2005 Dec;103(6):956-67. doi: 10.3171/jns.2005.103.6.0956.

  PMID: 16381181 RESULT

• Weaver FM, Stern MB, Follett K. Deep-brain stimulation in Parkinson's disease. Lancet Neurol. 2006 Nov;5(11):900-1. doi: 10.1016/S1474-4422(06)70586-5. No abstract available.

  PMID: 17052655 RESULT

• 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.

  PMID: 19126811 RESULT

• Genever RW. Deep brain stimulation for patients with advanced Parkinson disease. JAMA. 2009 May 20;301(19):1985; author reply 1985-6. doi: 10.1001/jama.2009.647. No abstract available.

  PMID: 19454631 RESULT

• 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.

  PMID: 20519680 RESULT

• Hou B, Jiang T, Liu R. Deep-brain stimulation for Parkinson's disease. N Engl J Med. 2010 Sep 2;363(10):987-8; author reply 988. doi: 10.1056/NEJMc1007650. No abstract available.

  PMID: 20830819 RESULT

• Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, Horak FB, Okun MS, Foote KD, Krack P, Pahwa R, Henderson JM, Hariz MI, Bakay RA, Rezai A, Marks WJ Jr, Moro E, Vitek JL, Weaver FM, Gross RE, DeLong MR. Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Arch Neurol. 2011 Feb;68(2):165. doi: 10.1001/archneurol.2010.260. Epub 2010 Oct 11.

  PMID: 20937936 RESULT

• Ostrem JL, Luo P, Weaver FM, Follett K, Rothlind J, Galifianakis NB, Lai EC, Bronstein J, Duda J, Holloway K, Sarwar A, Brodsky M, Chung K, Spindler M, Reda D, Snodgrass A, Moy C, Huang G, Wei Y, Marks WJ Jr; CSP 468F Study Group. 10-year clinical outcomes of subthalamic nucleus versus pallidal deep brain stimulation for Parkinson's disease: VA/NINDS CSP #468F. Front Neurol. 2026 Jan 16;16:1728999. doi: 10.3389/fneur.2025.1728999. eCollection 2025.

  PMID: 41626017 DERIVED

• 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.

  PMID: 25185211 DERIVED

• 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.

  PMID: 23667214 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Tremor; Dyskinesias

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

A limitation of this study is that the STN and GPi cases are pooled into a single DBS group. When the study was planned, it was thought that differences between STN and GPi at six months would be small, which was tested during the study analysis.

Results Point of Contact

• Title: Frances M. Weaver, Ph.D, Study Investigator
• Organization: Center for Management of Complex Chronic Care

Frances.Weaver@va.gov

(708) 202-2414

Study Officials

• Kenneth Follett

  VA Medical Center, Iowa City

  STUDY CHAIR

• Frances M. Weaver, PhD MA BA

  Edward Hines Jr. VA Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2003
• First Posted: March 19, 2003
• Study Start: April 1, 2002
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: May 9, 2014
• Results First Posted: July 30, 2013

Record last verified: 2014-04

Locations

US (14)