Clinical trial NCT00056563: Phase I Deep Brain Stimulation (DBS) vs. Best Medical Therapy (BMT) Trial
Official title: CSP #468 Phase I - A Comparison of Best Medical Therapy and Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus for the Treatment of Parkinson's Disease
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)
First posted: 2003-03-19
Enrollment: 255
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The Difference of Time Spent in the 'on' State Without Troublesome Dyskinesia Based on Patient Motor Diaries as Compared to the Baseline.
timeFrame: at six months
Secondary outcomes:
measure: The Change of Scores on the UPDRS for Blinded Assessed Motor Function 'Off' Medication and 'on' Stimulation
timeFrame: at six 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: VA Medical Center, San Francisco
state: California
city: San Francisco
country: United States
facility: University of California at 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: VA Medical Center, Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
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
affiliation: Edward Hines Jr. VA Hospital
name: Frances M. Weaver, PhD MA BA
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
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: 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.
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: 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.
citation: 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.
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.
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.