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

• ClinicalTrials.gov Identifier: NCT00056563
• Recruitment Status: Completed
• First Posted: March 19, 2003
• Results First Posted: July 30, 2013
• Last Update Posted: May 9, 2014
• Sponsor: US Department of Veterans Affairs
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): VA Office of Research and Development ( US Department of Veterans Affairs )

Tracking Information

• First Submitted Date: March 18, 2003
• First Posted Date: March 19, 2003
• Results First Submitted Date: May 20, 2013
• Results First Posted Date: July 30, 2013
• Last Update Posted Date: May 9, 2014
• Study Start Date: April 2002
• Actual Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 24, 2013): The Difference of Time Spent in the 'on' State Without Troublesome Dyskinesia Based on Patient Motor Diaries as Compared to the Baseline. [ Time Frame: at six months ]
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: July 24, 2013)

The Change of Scores on the UPDRS for Blinded Assessed Motor Function 'Off' Medication and 'on' Stimulation [ Time Frame: at six months ]

Unified Parkinson's Disease Rating Scale (UPDRS Part III) measured while the patient is off medications and on stimulation at follow-up visits post surgery. UPDRS Part III has 14 items assessing motor skills including facial expression and speech, tremors, rigidity, posture, gait, and bradykinesia. Left and right sides (arms, legs, and hands) are assessed separately for seven of the functions. A summary score ranging from 0 to 108 is generated by adding the 14 specific motor function responses. The motor function (UPDRS part III) assessments are done by turning on the stimulation with and without taking PD medications (on/off) at each in-person visit. The higher score indicates that the condition is worse.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Parkinson's Disease

Intervention

• Device: 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.
• Other: 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.

Study Arms

• Active Comparator: 1
  Deep Brain Stimulation
  Intervention: Device: Bilateral Deep Brain Stimulation
• Active Comparator: 2
  Best Medical Therapy
  Intervention: Other: best medical therapy

Publications *

• 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.
• 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.
• Weaver FM, Stern MB, Follett K. Deep-brain stimulation in Parkinson's disease. Lancet Neurol. 2006 Nov;5(11):900-1.
• 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.
• 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.
• 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.
• Follett K, Weaver FM, Stern M. Comment: Deep-brain stimulation for Parkinson's Disease. The New England journal of medicine. 2010 Sep 3; 363(10):988.
• 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. Review.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 24, 2013): 255
• Original Enrollment (submitted: June 23, 2005): 316
• Actual Study Completion Date: October 2008
• Actual Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 22 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00056563
• Other Study ID Numbers: 468 Phase I
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: VA Office of Research and Development ( US Department of Veterans Affairs )
• Study Sponsor: US Department of Veterans Affairs
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Study Chair: Kenneth Follett; VA Medical Center, Iowa City
• Study Chair: Frances M. Weaver, PhD MA BA; Edward Hines Jr. VA Hospital

• PRS Account: VA Office of Research and Development
• Verification Date: April 2014