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

NCT ID: NCT00056563

Last Updated: 2014-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 255 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-04-30
• Study Completion Date: 2008-10-31

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

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, 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 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 patients will then proceed into the surgical phase of the trial. 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. Patients will be followed for two years post surgery (24-30 months). 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. 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: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Deep Brain Stimulation

Group Type: ACTIVE_COMPARATOR

Bilateral Deep Brain Stimulation

Intervention Type: 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.

2

Best Medical Therapy

Group Type: ACTIVE_COMPARATOR

best medical therapy

Intervention Type: 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.

Interventions

Bilateral Deep Brain Stimulation

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.

Intervention Type: DEVICE

best medical therapy

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• "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.

• 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

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

Frances M. Weaver, PhD MA BA

Role: STUDY_CHAIR

Edward Hines Jr. VA Hospital

Locations

University of California at Los Angeles

Los Angeles, California, United States

VA Medical Center, San Francisco

San Francisco, California, United States

University of California at 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

VA Medical Center, Philadelphia

Philadelphia, Pennsylvania, United States

Pennsylvania Hospital

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

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.

Reference Type: RESULT

PMID: 16216957 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16381181 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17052655 (View on PubMed)

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)

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.

Reference Type: RESULT

PMID: 19454631 (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)

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.

Reference Type: RESULT

PMID: 20830819 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20937936 (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)

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: DERIVED

PMID: 23667214 (View on PubMed)

Other Identifiers

468 Phase I

Identifier Type: -

Identifier Source: org_study_id

NCT00101556

Identifier Type: -

Identifier Source: nct_alias