Clinical trial NCT00282152: 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
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Keywords: Early Stage Parkinson's Disease
Parkinson's Disease
Deep Brain Stimulation
PD
DBS
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2006-01-25
Enrollment: 37
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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).

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.

Primary outcomes:
measure: Safety: Time to Reach a 4 Point Increase (Worsening) in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score
timeFrame: baseline to 24 months
measure: Levodopa Equivalents, Change From Baseline
timeFrame: baseline to 24 months
Secondary outcomes:
measure: Change in UPDRS Part I, Mentation Behavior and Mood
timeFrame: baseline to 24 months
measure: Change in UPDRS Part II, Activities of Daily Living
timeFrame: baseline to 24 months
measure: Change in UPDRS Part III, Motor Examination, Excluding Rigidity
timeFrame: baseline to 24 months
measure: Change in UPDRS Part IV, Complications of Therapy
timeFrame: baseline to 24 months
measure: Change in Total UPDRS
timeFrame: baseline to 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Vanderbilt University Department of Neurology
name: P. David Charles, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.