NCT01076452

Brief Summary

The goal of the second phase of the study is to determine if simultaneous bilateral subthalamic nucleus stimulation or simultaneous bilateral globus pallidus stimulation is more effective in reducing symptoms of Parkinson's Disease.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
299

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Apr 2002

Longer than P75 for phase_3

Geographic Reach
1 country

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2002

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2008

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2009

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

February 24, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 26, 2010

Completed
3.9 years until next milestone

Results Posted

Study results publicly available

January 15, 2014

Completed
Last Updated

July 14, 2014

Status Verified

June 1, 2014

Enrollment Period

6.5 years

First QC Date

February 24, 2010

Results QC Date

September 11, 2013

Last Update Submit

June 27, 2014

Conditions

Parkinson's Disease

Keywords

Parkinson's Diseaselevo-dopatremordyskinesiasubthalamic nucleusglobus pallidus

Outcome Measures

Primary Outcomes (1)

  • The Change From Baseline in the UPDRS-III Score at 24 Months With Deep-brain Stimulation and Without Medication.

    The primary outcome measure for the comparison of GPi deep brain stimulation (DBS) to STN DBS is the motor function score of the 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. 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. A summary score ranging from 0 to 108 is generated by adding the 14 specific motor function responses. The higher score indicates the worse motor function.

    Baseline and 24 months

Secondary Outcomes (3)

  • The Change From Baseline in the UPDRS Scores Part I (Mentation) at 24 Months.

    Baseline and 24 months

  • The Change From Baseline in the UPDRS Scores Part II (Activity of Daily Living) at 24 Months.

    Baseline and 24 months

  • The Change From Baseline in the UPDRS Scores Part IV (Complication of Therapy) at 24 Months.

    Baseline and 24 months

Study Arms (2)

STN

ACTIVE COMPARATOR

Participants were randomized to receive deep brain stimulation on STN (Subthalamic Nucleus) target.

Device: Bilateral Deep Brain Stimulation

GPi

ACTIVE COMPARATOR

Participants were randomized to receive deep brain stimulation on GPi (Globus Pallidus) target.

Device: Bilateral Deep Brain Stimulation

Interventions

Bilateral Deep Brain StimulationDEVICE

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

GPiSTN

Eligibility Criteria

Age22 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • idiopathic Parkinson's Disease
  • Hoehn and Yahr stage 2 or worse when off medications
  • L-dopa responsive with clearly defined "on" periods (i.e. symptoms improve at least partially with L-dopa administration, a characteristic that helps distinguish idiopathic PD from "Parkinson's Plus" and atypical Parkinson's syndromes-see below)
  • persistent disabling symptoms (e.g. on troubling dyskinesias, or disabling "off" periods at least 3 hours/day) despite medication therapy. Patients will have been treated with variable doses of levodopa and dopamine agonists (at a minimum) and will have had an adequate trial of other adjunctive medications)
  • stable on medical therapy for at least one month prior to study enrollment
  • age \>21
  • available and willing to be followed-up according to study protocol

You may not qualify if:

  • "Parkinson's plus" syndromes, secondary, or atypical Parkinson's syndromes (e.g. progressive supranuclear palsy, striato-nigral degeneration, multiple system atrophy, post-stroke, post-traumatic, or post-encephalitic Parkinson's. These patients have cardinal symptoms characteristic of PD but with additional symptoms indicating other organic brain dysfunction, such as gaze palsies, autonomic dysfunction, lack of response to L-dopa, these individuals tend not to improve with standard treatments for PD)
  • previous Parkinson's Disease surgery
  • medical contraindications to surgery or stimulation (e.g. uncontrolled hypertension, advanced coronary artery disease, other implanted stimulation or electronically-controlled devices including cardiac demand pacemaker, aneurysm clips, cochlear implants, or a spinal cord stimulator) (Note: for the subject who receives either a pacemaker and/or defibrillator after this study enrollment, he/she will be allowed to continue the study if the neurostimulator system can be adequately programmed to permit system compatibility)
  • contraindication to magnetic resonance imaging (e.g. indwelling metal fragments or implants that might be affected by MRI)
  • active alcohol or drug abuse
  • score on Mini-Mental Status examination of 24 or lower, or other neuropsychological dysfunction 9e.g. dementia) that would contraindicate surgery
  • intracranial abnormalities that would contraindicate surgery (e.g. stroke, tumor, vascular abnormality affecting the target area)
  • pregnancy
  • concurrent participation in another research protocol

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

University of California at Los Angeles

Los Angeles, California, 90073, United States

Location

University of California at San Francisco

San Francisco, California, 94121, United States

Location

VA Medical Center, San Francisco

San Francisco, California, 94121, 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, 97207, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia, OPC

Philadelphia, Pennsylvania, 19106, 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, 23249, United States

Location

VA Puget Sound Health Care System, Seattle

Seattle, Washington, 98108, United States

Location

Related Publications (6)

  • 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: 19126811RESULT

  • 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: 20519680RESULT

  • Weaver FM, Follett KA, Stern M, Luo P, Harris CL, Hur K, 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. Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes. Neurology. 2012 Jul 3;79(1):55-65. doi: 10.1212/WNL.0b013e31825dcdc1. Epub 2012 Jun 20.

    PMID: 22722632RESULT

  • 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: 23667214RESULT

  • 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: 41626017DERIVED

  • 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: 25185211DERIVED

MeSH Terms

Conditions

Parkinson DiseaseTremorDyskinesias

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative DiseasesNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Limitations and Caveats

We observed differences between STN and GPi DBS groups on several secondary measures but these findings should be interpreted cautiously. We did not adjust for repeated significance tests and the differences may have limited clinical significance.

Results Point of Contact

Title
Frances M. Weaver, Ph.D
Organization
Hines Veterans Affairs Hospital Center for Management of Complex Chronic Care
frances.weaver@va.gov
708-202-8387

Study Officials

  • Kenneth Follett

    VA Medical Center, Iowa City

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
FED
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 24, 2010

First Posted

February 26, 2010

Study Start

April 1, 2002

Primary Completion

October 1, 2008

Study Completion

April 1, 2009

Last Updated

July 14, 2014

Results First Posted

January 15, 2014

Record last verified: 2014-06

Locations

US(14)