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

NCT00282152 | Completed Results DMC

• 3 other identifiers: 0407971363G050016
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Parkinson's Disease

Keywords

Early Stage Parkinson's Disease; Parkinson's Disease; Deep Brain Stimulation; PD; DBS

Outcome Measures

Primary Outcomes (2)

• 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.

  baseline to 24 months

• 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

  baseline to 24 months

Secondary Outcomes (5)

• Change in UPDRS Part I, Mentation Behavior and Mood

  baseline to 24 months

• Change in UPDRS Part II, Activities of Daily Living

  baseline to 24 months

• Change in UPDRS Part III, Motor Examination, Excluding Rigidity

  baseline to 24 months

• Change in UPDRS Part IV, Complications of Therapy

  baseline to 24 months

• Change in Total UPDRS

  baseline to 24 months

Study Arms (2)

ODT

ACTIVE COMPARATOR

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.

Drug: Optimal drug therapy

DBS+ODT

EXPERIMENTAL

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.

Device: B-STN DBS; Drug: Optimal drug therapy

Interventions

B-STN DBS DEVICE

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.

DBS+ODT

Optimal drug therapy DRUG

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.

DBS+ODT; ODT

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Related Publications (4)

• Hacker ML, Meystedt JC, Turchan M, Cannard KR, Harper K, Fan R, Ye F, Davis TL, Konrad PE, Charles D. Eleven-Year Outcomes of Deep Brain Stimulation in Early-Stage Parkinson Disease. Neuromodulation. 2023 Feb;26(2):451-458. doi: 10.1016/j.neurom.2022.10.051. Epub 2022 Dec 24.

  PMID: 36567243 DERIVED

• 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.

  PMID: 32601120 DERIVED

• 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.

  PMID: 28676842 DERIVED

• 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.

  PMID: 22104012 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: David Charles, MD
• Organization: Vanderbilt University Medical Center

david.charles@Vanderbilt.Edu

Study Officials

• P. David Charles, MD

  Vanderbilt University Department of Neurology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: January 23, 2006
• First Posted: January 25, 2006
• Study Start: March 1, 2006
• Primary Completion: January 1, 2012
• Study Completion: October 1, 2015
• Last Updated: May 30, 2017
• Results First Posted: May 30, 2017

Record last verified: 2017-03