Safety and Tolerability of Neurostimulation in Early Stage Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 37
- 主要终点
- Safety: Time to Reach a 4 Point Increase (Worsening) in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
ODT
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.
干预措施: Optimal drug therapy (Drug)
DBS+ODT
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.
干预措施: B-STN DBS (Device)
DBS+ODT
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.
干预措施: Optimal drug therapy (Drug)
结局指标
主要结局
Safety: Time to Reach a 4 Point Increase (Worsening) in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score
时间窗: baseline to 24 months
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
时间窗: baseline to 24 months
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
次要结局
- 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)
研究者
David Charles
Associate Professor of Neurology
Vanderbilt University Medical Center