A Multidisciplinary Approach to Manage Gait Difficulty in Parkinson Patients
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Freezing of Gait
研究概览
简要总结
The study team proposes to treat Parkinson's patients with gait difficulty with multidisciplinary approach of medications. Single medication treatment, such as the use of cholinergic-boosting anti-dementia medication targeting cholinergic deficiency to improve executive dysfunction and attention deficit, or the use of medication boosting the norepinephrine system, have not proven effective so far in treating the gait difficulty. Anti-anxiety medications, particularly the SNRI (serotonin and norepinephrine reuptake inhibitor) medications, which also ameliorate the norepinephrinergic deficiency, have not been studied except for one successful case report using duloxetine to treat primary progressive freezing of gait.
Targeting multiple mechanisms at same time, such as the combination of a SNRI antianxiety medication (also boosting the norepinephrine system, such as duloxetine) with an anti-dementia medication correcting the cholinergic deficiency (such as donepezil), or targeting a new mechanism, such as the use of anti-GABAergic medication targeting the area responsible for gait and sleep cycle (pedunculopontine nucleus area, PPNa) should be tried.
Therefore, a collaboration of multidisciplinary teams among the neurology movement disorder team and cognition and sleep team, and psychiatry team is essential, which has not been tried before in studying and treating the challenging gait difficulty in Parkinson patients.
详细描述
The study team proposes to treat parkinsonian patients with gait difficulty of FOG with the SNRI anti-anxiety medication duloxetine for 4 weeks, followed by an additional anti-dementia medication donepezil for 2 weeks to determine whether antianxiety treatment alone or in combination with the anti-dementia medication can improve gait. Another medication with GABA antagonist property targeting the gait controlling area PPNa (and improving anxiety and cognition as well), modafinil, will be tried for 2 weeks after a 4-week washout period of the previous medications.
Specifically, the investigators will propose an open label prospective pilot study using duloxetine to treat 22 parkinsonian patients with FOG, aiming for estimated 80% power of detecting 50%. Each patient will take duloxetine 30mg for 1 week, followed by 60mg qam for 1 week, 90mg qam for 1 week, and 120mg qam for 1 week, if tolerated. The patient will be taking duloxetine for a total of 4 weeks, as described above. The dose of duloxetine will be reduced if the patient cannot tolerate a higher rank dose as designated. This principle will apply to the other two medications used in the study as well. Donepezil will then be added to duloxetine 120mg qam (or the highest dose the patient can tolerate if it is lower than 120mg) by 5mg qd for 1 week, followed by 10mg qd for 1 week. Each patient will visit us 3 times (baseline and at the end of each medication, namely 4 weeks after the duloxetine and 2 weeks after the donepezil), checking UPDRS-III (and PSP scale as well for PSP patients), stand-walk-sit, freezing of gait questionnaire, Montreal cognitive scale (MoCA) for patients before and after Donepezil treatment, and anxiety scale for patients before and after duloxetine treatment (if the patient is on dopaminergic medication). Daily falls, freezing of gait (by the questionnaire) and quality of life (by PDQ-39 scale) over the past week prior to the clinical visit will also be checked.
After a 4-week washout period, each patient will take modafinil 100mg qam for 1 week, followed by 200mg qam for 1 week. Each patient will visit us twice (baseline at the end of the 4-week washout period, and at the end of the 2-week modafinil treatment), checking UPDRS (and PSP scale as well if for PSP patient), stand-walk-sit, freezing of gait questionnaire, MoCA, anxiety scale and Epworth sleep scale at each visit before and 1 hour after the dopaminergic medication(s) (if the patient is on dopaminergic medication). Daily falls, freezing of gait and quality of life (by PDQ-39) over the past week prior to the clinical visit will also be checked.
A paired t-test will be used to compare the changes under each regimen with that at baseline, with primary outcome on gait difficulty of FOG frequency and severity, and secondary outcome on anxiety, cognition, UPDRS-III (plus PSP scale for PSP patients), and Epworth sleep scale (for modafinil trial) at dopaminergic medication off (after staying off the dopaminergic medication for over night) and on (1 hour after taking dopaminergic medication) state and quality of life assessment. The investigators want to see if the medications of different working mechanism, along or in combination, could improve the FOG and other motor symptoms, through the improvement of anxiety, cognitive dysfunction and wakening state at dopaminergic medications (for parkinsonism) off state and on state.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parkinsonian patient with Parkinson's disease per UK brain bank criteria 15,
- •or PSP per SPSP-NINDS criteria 16,
- •FOG at off or on dopaminergic medication or both.
排除标准
- •Patients with psychosis,
- •unable to walk without assistance,
- •seizures,
- •or allergy to any of these three medications on trial.
研究组 & 干预措施
Open-Label Treatment Arm
Each patient will take Duloxetine 30mg for 1 week, followed by 60mg qam for 1 week, 90mg qam for 1 week, and 120mg qam for 1 week, if tolerated. The patient will be taking Duloxetine for a total of 4 weeks. The dose of Duloxetine will be reduced if the patient cannot tolerate. Donepezil will then be added to Duloxetine 120mg qam (or the highest dose the patient can tolerate) by 5mg qd for 1 week, followed by 10mg qd for 1 week.
After a 4-week washout period, each patient will take Modafinil 100mg qam for one week, followed by 200mg qam for 1 week.
Patients will come into the medical center on 5 occasions, 1 for screening/baseline, 1 after completion of duloxetine, 1 after completion of duloxetine+donepezil, 1 after four-week washout, 1 after completion of modafinil.
干预措施: Duloxetine (Drug)
Open-Label Treatment Arm
Each patient will take Duloxetine 30mg for 1 week, followed by 60mg qam for 1 week, 90mg qam for 1 week, and 120mg qam for 1 week, if tolerated. The patient will be taking Duloxetine for a total of 4 weeks. The dose of Duloxetine will be reduced if the patient cannot tolerate. Donepezil will then be added to Duloxetine 120mg qam (or the highest dose the patient can tolerate) by 5mg qd for 1 week, followed by 10mg qd for 1 week.
After a 4-week washout period, each patient will take Modafinil 100mg qam for one week, followed by 200mg qam for 1 week.
Patients will come into the medical center on 5 occasions, 1 for screening/baseline, 1 after completion of duloxetine, 1 after completion of duloxetine+donepezil, 1 after four-week washout, 1 after completion of modafinil.
干预措施: Donepezil (Drug)
Open-Label Treatment Arm
Each patient will take Duloxetine 30mg for 1 week, followed by 60mg qam for 1 week, 90mg qam for 1 week, and 120mg qam for 1 week, if tolerated. The patient will be taking Duloxetine for a total of 4 weeks. The dose of Duloxetine will be reduced if the patient cannot tolerate. Donepezil will then be added to Duloxetine 120mg qam (or the highest dose the patient can tolerate) by 5mg qd for 1 week, followed by 10mg qd for 1 week.
After a 4-week washout period, each patient will take Modafinil 100mg qam for one week, followed by 200mg qam for 1 week.
Patients will come into the medical center on 5 occasions, 1 for screening/baseline, 1 after completion of duloxetine, 1 after completion of duloxetine+donepezil, 1 after four-week washout, 1 after completion of modafinil.
干预措施: Modafinil (Drug)
结局指标
主要结局
Freezing of Gait
时间窗: From baseline to completion of drug regimen (4 weeks of duloxetine, 2 weeks of duloxetine & donepezil, 2 weeks & 3 days modafinil)
Changes in the score of the FOG questionnaire compared to the baseline, at on and off PD medications status.
次要结局
- Change in quality of life(From baseline to completion of drug regiment (4 weeks of duloxetine, 2 weeks of duloxetine & donepezil, 2 weeks & 3 days modafinil))
- Change in anxiety(From baseline to completion of drug regiment (4 weeks of duloxetine, 2 weeks of duloxetine & donepezil, 2 weeks & 3 days modafinil))
- Change in symptom score/severity(From baseline to completion of drug regiment (4 weeks of duloxetine, 2 weeks of duloxetine & donepezil, 2 weeks & 3 days modafinil))
- Change in sleep quality(From baseline to completion of drug regiment (4 weeks of duloxetine, 2 weeks of duloxetine & donepezil, 2 weeks & 3 days modafinil))
- Change in cognition(From baseline to completion of drug regiment (4 weeks of duloxetine, 2 weeks of duloxetine & donepezil, 2 weeks & 3 days modafinil))