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

Parkinson's Disease Clinical 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00056563
• Other study ID #: 468 Phase I
• Status: Completed
• Phase: Phase 3
• First received: March 18, 2003
• Last updated: April 24, 2014
• Start date: April 2002
• Est. completion date: October 2008

Study information

• Verified date: April 2014
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Other known NCT identifiers

• NCT00101556

Recruitment information / eligibility

• Status: Completed
• Enrollment: 255
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 22 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• 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.

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	Michael E. DeBakey VA Medical Center (152)	Houston	Texas
United States	VA Medical Center, Iowa City	Iowa City	Iowa
United States	University of California at Los Angeles	Los Angeles	California
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	VA Medical Center, Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	VA Medical Center, Portland	Portland	Oregon
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	Medical College of Virginia	Richmond	Virginia
United States	University of California at San Francisco	San Francisco	California
United States	VA Medical Center, San Francisco	San Francisco	California
United States	VA Puget Sound Health Care System, Seattle	Seattle	Washington
United States	VA Greater Los Angeles Healthcare System, West LA	West Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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 Pa — View 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. — View Citation

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.

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, — View 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. — View 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 d — View Citation

Weaver FM, Rothlind J, Stern M. Deep Brain Stimulation for Patients with Advanced Parkinson Disease Reply. [Letter to the Editor]. JAMA : the journal of the American Medical Association. 2009 May 20; 301(19):1985.

Weaver FM, Stern MB, Follett K. Deep-brain stimulation in Parkinson's disease. Lancet Neurol. 2006 Nov;5(11):900-1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	The Change of Scores on the UPDRS for Blinded Assessed Motor Function 'Off' Medication and 'on' Stimulation	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.	at six months	No