Efficacy of Deep Brain Stimulation and Levodopa on Freezing of Gait in Advanced Parkinson's Disease: a Comparative Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Time spent with FOG during protocol
研究概览
简要总结
Freezing of gait (FoG) is a complex symptom of Parkinson's disease (PD) that cause falls and disability in PD patients, heavily affect patients' autonomy and quality of life. Gait disturbances and FoG are difficult to manage as they usually do not complete respond to both dopaminergic treatment and subthalamic nucleus deep brain stimulation (STN-DBS). One therapeutic strategy suggested in literature for improving gait disturbances is to increase the dose of dopaminergic drugs according to the hypothesis of pseudo-ON-freezing. The pseudo-ON-FoG in patients treated with STN-DBS can easily occur as the result of a suboptimal stimulation or the consequence of a post-operative reduction of the dopaminergic therapy. Therefore, it is reasonable hypothesize both the increase of stimulation and levodopa as good therapeutic strategies to improve pseudo-ON-FoG. At present there are no evidence for suppose that one option is better than the other, even though two recent studies on gait analysis reported a positive additive effect of levodopa therapy on gait parameters in patients treated with STN-DBS.
In this study, the investigators aim to objectively evaluating the improvement of FoG in PD patients treated with STN-DBS at different treatment conditions consisting of increased intensity of stimulation or higher dosage of levodopa.
详细描述
This is a cross-over, blind, randomized study to evaluate the improvement of FoG in a group of PD patients treated with bilateral STN-DBS by increasing the intensity of stimulation (STIM plus) or administering a higher dose of levodopa (MED plus).
Patient will be videorecorded for evaluation of freezing episodes and gait cinematic parameters by means of 3 wearable inertial sensors on the feet and at lumbar level during a standardized walking protocol including: Timed Up and Go, Turn 360°, Gait 18 m and a Complex task in single task and dual task (serial-3 subtractions) conditions. In each condition, Tinetti scale, Trail Making Test, alternate fluency test, Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) and MDS Unified Dyskinesia Rating Scale (UDysRS) will be also perform.
In addition, other demographic and clinical information such as age, sex, MMSE, MoCA, New Freezing of Gait Questionnaire, Falls Efficacy Scale will be collected.
The primary endpoint of this study is to investigate the efficacy of increasing intensity of stimulation (STIM plus) or levodopa (MED plus) on freezing of gait (FOG).
Secondary outcome measures include cinematic gait parameters, global motor outcomes and cognitive functions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The count and duration of FoG episodes during the standardize walking protocol is measured on video-assessment by two blind raters.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with Parkinson's disease treated with STN-DBS who achieved a good control of motor fluctuations and cardinal motor symptoms (bradykinesia, rigidity, tremor)
- •History of FoG in daily-ON condition after optimal DBS programming, defined by a score of 1 on Question 1 and score ≥ 2 on Question 2 of the New Freezing of Gait Questionnaire.
排除标准
- •inability to walk independently for 10 meters.
- •limited therapeutic windows of stimulation without the possibility of increase the intensity of stimulation of 0,5 mA for the appearance of side effects
- •previous evidence of severe adverse effects with high levodopa dose ore increased STN-DBS intensity, such as psychosis, hallucinations, painful dyskinesias, severe hypotension, digestive symptoms.
- •dementia (MMSE score ≤ 18)
研究组 & 干预措施
STIM ON plus/MED ON plus
Patients were evaluated in two following morning sessions under different treatment conditions:
- STIM ON plus (intervention 1)
- MED ON plus (intervention 2)
干预措施: STIM ON plus (Device)
STIM ON plus/MED ON plus
Patients were evaluated in two following morning sessions under different treatment conditions:
- STIM ON plus (intervention 1)
- MED ON plus (intervention 2)
干预措施: MED ON plus (Drug)
MED ON plus/STIM ON plus
Patients were evaluated in two following morning sessions under different treatment conditions:
- MED ON plus (intervention 2)
- STIM ON plus (intervention 1)
干预措施: STIM ON plus (Device)
MED ON plus/STIM ON plus
Patients were evaluated in two following morning sessions under different treatment conditions:
- MED ON plus (intervention 2)
- STIM ON plus (intervention 1)
干预措施: MED ON plus (Drug)
结局指标
主要结局
Time spent with FOG during protocol
时间窗: immediate post monitoring
Video-assessed reduction in the total time of FoG during the standardize walking protocol in MED ON plus or STIM ON plus condition compared to baseline.
次要结局
- Trail Making test A and B(immediate post monitoring)
- Gait performance(immediate post monitoring)
- MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III(immediate post monitoring)
- Patient global impression of change (PGI-C)(immediate post monitoring)
- Phonemic/Semantic alternate Fluency test(immediate post monitoring)
研究者
Ilaria Cani
Principal Investigator
IRCCS Istituto delle Scienze Neurologiche di Bologna