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Deep Brain Stimulation (DBS) for Early Stage Parkinson's Disease (PD)

Primary Purpose

Parkinson's Disease

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
B-STN DBS
Optimal drug therapy
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Parkinson's Disease focused on measuring Early Stage Parkinson's Disease, Parkinson's Disease, Deep Brain Stimulation, PD, DBS

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have a clinical diagnosis of probable idiopathic PD. Demonstrated response to dopaminergic therapy, defined as demonstrating at least 30% improvement in parkinsonian motor signs, based upon the UPDRS motor examination subscore, following the administration of their dopamine agonist (DA) drug(s) during the screening neurological examination. Hoehn and Yahr (H&Y) stage II when OFF medication. No contraindications to surgery. Age between 50 and 75 years old. Available for follow-up for four years. Informed Consent: The subject understands the risks, benefits, and alternatives to the study procedures and participation in the study. MRI within normal range for age. Levodopa or dopamine agonist therapy for greater than six months but less than or equal to four years. Exclusion Criteria: Evidence of an alternative diagnosis or secondary parkinsonism, as suggested by features unusual early in the clinical course: Prominent postural instability, freezing phenomena, or hallucinations unrelated to medications in the first 3 years after symptom onset; dementia preceding motor symptoms; supranuclear gaze palsy (other than restriction of upward gaze) or slowing of vertical saccades in the first year; severe, symptomatic dysautonomia unrelated to medications; documentation of a condition known to produce parkinsonism and plausibly connected to the subject's symptoms (such as suitably located focal brain lesions or neuroleptic use within the past 6 months) Uncontrolled medical condition or clinically significant medical disease that would increase the risk of developing pre- or postoperative complications (e.g., significant cardiac or pulmonary disease, uncontrolled hypertension). Evidence of dementia Major psychiatric disorder Previous brain operation or injury. Active participation in another clinical trial for the treatment of PD. Patients who have demand cardiac pacemakers or implantable cardioverter defibrillators (ICD's). Patients who have medical conditions that require repeat MRI scans or diathermy treatments. Evidence of existing dyskinesias or motor fluctuations.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    ODT

    DBS+ODT

    Arm Description

    Optimal drug therapy: The drugs used on this study are not investigational. They are drugs for Parkinson's disease that are standard of care. The drug form, dosage, frequency and duration will vary.

    Subjects receive bilateral subthalamic nucleus (B-STN) DBS and continue to take optimal drug therapy as prescribed by their treating neurologist. B-STN DBS: Deep brain stimulation (DBS) of both the right and left sub-thalamic nucleus (STN) is an FDA approved treatment for mid- and advanced PD. DBS is not approved for early stage PD. In mid- and advanced stage Parkinson's disease, using DBS in this area of the brain lessens symptoms and allows patients to take less drug to control the disease. Dosage and frequency are not applicable to the DBS. Once the DBS is placed, unless deemed necessary, it will not be removed. Optimal drug therapy: The drugs used on this study are not investigational. They are drugs for Parkinson's disease that are standard of care. The drug form, dosage, frequency and duration will vary.

    Outcomes

    Primary Outcome Measures

    Safety: Time to Reach a 4 Point Increase (Worsening) in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score
    The primary hypothesis of this feasibility trial was focused on safety and tolerability and that the DBS+ODT group would not worsen more quickly than the ODT group.
    Levodopa Equivalents, Change From Baseline
    100 mg of levodopa with a dopa-decarboxylase inhibitor = 133 mg of controlled-release levodopa preparations = total levodopa dose + (total levodopa dose x 0.33) of levodopa with dopa-decarboxylase and entacapone = 1 mg of pergolide, pramipexole, or lisuride = 5 mg of ropinirole = 3.3 mg of rotigotine

    Secondary Outcome Measures

    Change in UPDRS Part I, Mentation Behavior and Mood
    Score: 0-16 0 =normal, 16 = most disability
    Change in UPDRS Part II, Activities of Daily Living
    Score: 0-52 0 =normal, 52 = most limited
    Change in UPDRS Part III, Motor Examination, Excluding Rigidity
    Score: 0-56 0 = full movement, 56 = most limited
    Change in UPDRS Part IV, Complications of Therapy
    Score: 0-23 0 =no complications, 23 = most complications
    Change in Total UPDRS
    The Total Unified Parkinson's Disease Rating Scale (UPDRS) is a composite scale, consisting of four sections that evaluate mood and behavior, activities of daily living, motor symptoms, and complications of medical therapy. Range is 0 to 16, with 16 being maximal disability

    Full Information

    First Posted
    January 23, 2006
    Last Updated
    April 19, 2017
    Sponsor
    Vanderbilt University Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00282152
    Brief Title
    Deep Brain Stimulation (DBS) for Early Stage Parkinson's Disease (PD)
    Official Title
    Safety and Tolerability of Neurostimulation in Early Stage Parkinson's Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    March 2006 (undefined)
    Primary Completion Date
    January 2012 (Actual)
    Study Completion Date
    October 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Vanderbilt University Medical Center

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Bilateral subthalamic nucleus deep brain stimulation (B-STN DBS) is one of the most effective surgical treatments for PD patients suffering from levodopa-induced motor complications. The relatively low incidence of permanent adverse effects and the potential for neuroprotection and alteration of the natural course of PD suggest a highly favorable benefit-to-risk ratio of this procedure. Since neuroprotection is best applied early in the disease course when there are more surviving neurons, we believe that further investigation of this procedure is warranted. The proposed pilot study will provide the necessary data to substantiate the safety and tolerability of the procedure as well as provide data for the design of a full-scale, multicenter trial to investigate the hypothesis that B-STN DBS is a safe and effective treatment to slow the progression of PD.
    Detailed Description
    This pilot trial is designed specifically to collect the preliminary safety and tolerability data necessary to conduct a future phase III clinical trial to investigate the hypothesis that deep brain stimulation of the subthalamic nucleus in subjects with early Parkinson's will slow the progression of the disease. The study design is a prospective, randomized, blinded, single-center trial comparing the safety and tolerability of B-STN DBS + Optimal Drug Therapy (ODT) vs. (ODT) alone (control, standard of care) in 30 subjects (15 per group) with early PD (Hoehn and Yahr stage II when off medication).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Parkinson's Disease
    Keywords
    Early Stage Parkinson's Disease, Parkinson's Disease, Deep Brain Stimulation, PD, DBS

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    37 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    ODT
    Arm Type
    Active Comparator
    Arm Description
    Optimal drug therapy: The drugs used on this study are not investigational. They are drugs for Parkinson's disease that are standard of care. The drug form, dosage, frequency and duration will vary.
    Arm Title
    DBS+ODT
    Arm Type
    Experimental
    Arm Description
    Subjects receive bilateral subthalamic nucleus (B-STN) DBS and continue to take optimal drug therapy as prescribed by their treating neurologist. B-STN DBS: Deep brain stimulation (DBS) of both the right and left sub-thalamic nucleus (STN) is an FDA approved treatment for mid- and advanced PD. DBS is not approved for early stage PD. In mid- and advanced stage Parkinson's disease, using DBS in this area of the brain lessens symptoms and allows patients to take less drug to control the disease. Dosage and frequency are not applicable to the DBS. Once the DBS is placed, unless deemed necessary, it will not be removed. Optimal drug therapy: The drugs used on this study are not investigational. They are drugs for Parkinson's disease that are standard of care. The drug form, dosage, frequency and duration will vary.
    Intervention Type
    Device
    Intervention Name(s)
    B-STN DBS
    Intervention Description
    Deep brain stimulation (DBS) of both the right and left sub-thalamic nucleus (STN) is an FDA approved treatment for advanced PD. In mid- and advanced stage Parkinson's disease, using DBS in this area of the brain lessens symptoms and allows patients to take less drug to control the disease. Dosage and frequency are not applicable to the DBS. Once the DBS is placed, unless deemed necessary, it will not be removed.
    Intervention Type
    Drug
    Intervention Name(s)
    Optimal drug therapy
    Intervention Description
    The drugs used on this study are not investigational. They are drugs for Parkinson's disease that are standard of care. The drug form, dosage, frequency and duration will vary. Examples of drugs used include carbidopa/levodopa, pramipexole, ropinirole, and selegiline.
    Primary Outcome Measure Information:
    Title
    Safety: Time to Reach a 4 Point Increase (Worsening) in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score
    Description
    The primary hypothesis of this feasibility trial was focused on safety and tolerability and that the DBS+ODT group would not worsen more quickly than the ODT group.
    Time Frame
    baseline to 24 months
    Title
    Levodopa Equivalents, Change From Baseline
    Description
    100 mg of levodopa with a dopa-decarboxylase inhibitor = 133 mg of controlled-release levodopa preparations = total levodopa dose + (total levodopa dose x 0.33) of levodopa with dopa-decarboxylase and entacapone = 1 mg of pergolide, pramipexole, or lisuride = 5 mg of ropinirole = 3.3 mg of rotigotine
    Time Frame
    baseline to 24 months
    Secondary Outcome Measure Information:
    Title
    Change in UPDRS Part I, Mentation Behavior and Mood
    Description
    Score: 0-16 0 =normal, 16 = most disability
    Time Frame
    baseline to 24 months
    Title
    Change in UPDRS Part II, Activities of Daily Living
    Description
    Score: 0-52 0 =normal, 52 = most limited
    Time Frame
    baseline to 24 months
    Title
    Change in UPDRS Part III, Motor Examination, Excluding Rigidity
    Description
    Score: 0-56 0 = full movement, 56 = most limited
    Time Frame
    baseline to 24 months
    Title
    Change in UPDRS Part IV, Complications of Therapy
    Description
    Score: 0-23 0 =no complications, 23 = most complications
    Time Frame
    baseline to 24 months
    Title
    Change in Total UPDRS
    Description
    The Total Unified Parkinson's Disease Rating Scale (UPDRS) is a composite scale, consisting of four sections that evaluate mood and behavior, activities of daily living, motor symptoms, and complications of medical therapy. Range is 0 to 16, with 16 being maximal disability
    Time Frame
    baseline to 24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    50 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients must have a clinical diagnosis of probable idiopathic PD. Demonstrated response to dopaminergic therapy, defined as demonstrating at least 30% improvement in parkinsonian motor signs, based upon the UPDRS motor examination subscore, following the administration of their dopamine agonist (DA) drug(s) during the screening neurological examination. Hoehn and Yahr (H&Y) stage II when OFF medication. No contraindications to surgery. Age between 50 and 75 years old. Available for follow-up for four years. Informed Consent: The subject understands the risks, benefits, and alternatives to the study procedures and participation in the study. MRI within normal range for age. Levodopa or dopamine agonist therapy for greater than six months but less than or equal to four years. Exclusion Criteria: Evidence of an alternative diagnosis or secondary parkinsonism, as suggested by features unusual early in the clinical course: Prominent postural instability, freezing phenomena, or hallucinations unrelated to medications in the first 3 years after symptom onset; dementia preceding motor symptoms; supranuclear gaze palsy (other than restriction of upward gaze) or slowing of vertical saccades in the first year; severe, symptomatic dysautonomia unrelated to medications; documentation of a condition known to produce parkinsonism and plausibly connected to the subject's symptoms (such as suitably located focal brain lesions or neuroleptic use within the past 6 months) Uncontrolled medical condition or clinically significant medical disease that would increase the risk of developing pre- or postoperative complications (e.g., significant cardiac or pulmonary disease, uncontrolled hypertension). Evidence of dementia Major psychiatric disorder Previous brain operation or injury. Active participation in another clinical trial for the treatment of PD. Patients who have demand cardiac pacemakers or implantable cardioverter defibrillators (ICD's). Patients who have medical conditions that require repeat MRI scans or diathermy treatments. Evidence of existing dyskinesias or motor fluctuations.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    P. David Charles, MD
    Organizational Affiliation
    Vanderbilt University Department of Neurology
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    32601120
    Citation
    Hacker ML, Turchan M, Heusinkveld LE, Currie AD, Millan SH, Molinari AL, Konrad PE, Davis TL, Phibbs FT, Hedera P, Cannard KR, Wang L, Charles D. Deep brain stimulation in early-stage Parkinson disease: Five-year outcomes. Neurology. 2020 Jul 28;95(4):e393-e401. doi: 10.1212/WNL.0000000000009946. Epub 2020 Jun 29.
    Results Reference
    derived
    PubMed Identifier
    28676842
    Citation
    Millan SH, Hacker ML, Turchan M, Molinari AL, Currie AD, Charles D. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index. Parkinsons Dis. 2017;2017:7163801. doi: 10.1155/2017/7163801. Epub 2017 Jun 6.
    Results Reference
    derived
    PubMed Identifier
    22104012
    Citation
    Charles PD, Dolhun RM, Gill CE, Davis TL, Bliton MJ, Tramontana MG, Salomon RM, Wang L, Hedera P, Phibbs FT, Neimat JS, Konrad PE. Deep brain stimulation in early Parkinson's disease: enrollment experience from a pilot trial. Parkinsonism Relat Disord. 2012 Mar;18(3):268-73. doi: 10.1016/j.parkreldis.2011.11.001. Epub 2011 Nov 21.
    Results Reference
    derived

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    Deep Brain Stimulation (DBS) for Early Stage Parkinson's Disease (PD)

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