Effectiveness of Onabotulinumtoxin A on Reduction of Rest Tremor in Parkinson's Disease: a Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Change in the MDS-UPDRS Tremor Subscore
研究概览
简要总结
Purpose: Rest tremor in Parkinson's disease is notoriously difficult to treat through pharmacological measures, currently only predictably attenuated by the invasive deep brain stimulation surgery. The investigators hope to find some predictable and clinically meaningful attenuation of tremor with targeted use of onabotulinum toxin on muscles involved in creating the tremor.
Participants: 16 subjects who meet United Kingdom (UK) brain bank criteria for Parkinson's disease with medically refractory rest tremor of at least 3 cm amplitude.
Procedures (methods): Subjects will be blinded to receive either sham saline injection versus onabotulinum toxin injections directed to muscle groups felt to be clinically involved in causing the oscillatory movement of the tremor. Assessment of tremor severity and functional improvement from baseline after injection will occur within group (i.e. each subject will serve as their own control).
Hypotheses:
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(A) Onabotulinumtoxin A significantly attenuates the amplitude of medically-refractory rest tremor of the upper limb in Parkinson's patients as compared to sham injections; as measured by reduction in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) tremor subscore.
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(B) Onabotulinumtoxin A significantly improves the limb function of Parkinson's patients with medically-refractory rest tremor of the upper limb as compared to sham injections; as measured by an increase in Action Research Arm Test (ARAT) scores.
详细描述
For purposes of properly identifying muscles intended for injection, a portable electromyography will be attached to an appropriate gauge electromyography-guided botulinum toxin needle, which in turn will be used to hear/see motor evoked potentials (MEPs). Subjects will be asked to activate the muscle while needle is inserted to ensure proper placement of the needle in the desired muscle prior to injection of study solution.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blinded study whereby the subject, the movement disorder specialist injecting neurotoxin, and the movement disorder specialist rating the patient will be unaware of the solution injected and/or planned for injection same day. To ensure that the injecting specialist is blinded to the solution, syringes will be premixed by a separate member of the research team and de-identified of any possible labels that would indicate the properties of the solution being administered to the subject.
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 45 years of age, and no more than 80 years of age.
- •Meet UK Parkinson's disease brain bank diagnostic criteria
- •Have clinical evidence of rest tremor of one or both upper extremities defined as involuntary, rhythmic oscillations about any joint within the upper extremities
- •Rest tremor amplitude must be at minimum 3 cm as determined by expert opinion by a movement disorders specialist. Confirmation of amplitude measurement will be obtained from the Px1 prior to active participation in the study but will not be used for inclusion/exclusion in study participation.
- •Rest tremor must be historically refractory to at least 2 categories of medications typically used as anti-parkinsonian agents including levodopa formulations, dopamine agonists, amantadine, and anticholinergics.
- •Participants must be able to make no changes to their anti-parkinsonian medications for 150 days (study duration). Ability and safety to do so must also be determined by the participant's treating physician and confirmed in writing prior to participating.
- •Able to provide informed consent
排除标准
- •History of having undergone botulinum toxin injections for any other condition previously
- •Allergy to carbidopa or levodopa.
- •Prescreening Montreal Cognitive Assessment (MoCA) score less than 22
- •Prescreening muscle weakness as determined by Medical Research Council grade less than 5/5 on direct testing in the upper limb afflicted with rest tremor.
- •Pregnancy: documentation of non-pregnancy by urine pregnancy test will be obtained from all women of child-bearing potential prior to participation
- •Infection at the proposed injection site
- •Those with a pre-existing, concomitant neuromuscular disorder
- •Compromised respiratory function
- •History of having undergone deep brain stimulation surgery for any condition
研究组 & 干预措施
Onabotulinumtoxin A Injection, then Placebo
Participants first receive Onabotulinumtoxin A Injection and following a 3-month washout, they receive Placebo
干预措施: Onabotulinumtoxin A Injection (Drug)
Onabotulinumtoxin A Injection, then Placebo
Participants first receive Onabotulinumtoxin A Injection and following a 3-month washout, they receive Placebo
干预措施: Placebo (Other)
Placebo, then Onabotulinumtoxin A Injection
Participants first receive placebo injection and following a 3-month washout, they receive Onabotulinumtoxin A Injection.
干预措施: Onabotulinumtoxin A Injection (Drug)
Placebo, then Onabotulinumtoxin A Injection
Participants first receive placebo injection and following a 3-month washout, they receive Onabotulinumtoxin A Injection.
干预措施: Placebo (Other)
结局指标
主要结局
Change in the MDS-UPDRS Tremor Subscore
时间窗: Prior to onabotulinumtoxinA injection and at 30 days after injection
The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III's tremor subscore (3.17). The subscale has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Higher MDS-UPDRS scores reflect worse tremor/motor function. Larger differences will infer greater effect size for the intervention. Score drops over time imply improvement in tremor/motor function.
次要结局
- Change in Tremor Amplitude in Centimeters (cm) as Measured by Px1(Prior to onabotulinumtoxinA injection and at 30 days after injection)
- Change in the ARAT Score(Prior to onabotulinumtoxinA injection and at 30 days after injection)
- Correlation Between MDS-UPDRS Tremor Subscore and Px1 Tremor Amplitude(At Visit 1, prior to 1st injection through Visit 4, 30 days after last injection)
- Change in Tremor Frequency in Hertz (Hz) as Measured by Px1(Prior to onabotulinumtoxinA injection and at 30 days after injection)