A Phase II, Double-Blind, Placebo-Controlled, Crossover Study to Assess Clinical Benefit and Safety of Droxidopa in the Treatment of Parkinson's Disease
试验速览
- 阶段
- 2 期
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Change from baseline in freezing of gait symptoms using Freezing of Gait Questionnaire
研究概览
简要总结
Since droxidopa has been approved in Japan for treating freezing of gait in Parkinson's disease patients, this is to confirm and further investigate the safety and efficacy using a similar dose. The possible beneficial effects on cognition in mildly cognitively impaired Parkinson's disease patients will also be tested, since this problem in Parkinson's disease may be associated with decreased brain synthesis of norepinephrine (a neurotransmitter associated with multiple brain functions).
During this 11 week study, droxidopa will be slowly titrated up to 600 mg daily. Walking and freezing of gait will be evaluated and rated. Cognitive functions will be evaluated by a computer-based program.
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)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provide written informed consent to participate in the study
- •Diagnosed with probable levodopa-responsive idiopathic PD (meeting United Kingdom PD Brain Bank diagnostic criteria), and receiving levodopa therapy for this disorder. Other PD medications can also be used.
- •Must have AT LEAST ONE of below two criteria:
- •At least 3 months incidence of typical freezing of gait symptoms, occurring while levodopa is otherwise providing an "on" mobility state (including at least one of the following Freezing of Gait patterns: start hesitancy, freezing at making turns or when passing through a doorway, spontaneous freezing during continued walking, or Freezing of Gait related to a simultaneous mental or physical activity) OR
- •Have a screening score between 22 and 26 (inclusive) on the Montreal Cognitive Assessment
排除标准
- •Taking direct acting vasoconstriction agent (i.e. ephedrine or midodrine). Subjects taking vasoconstrictor agents such as ephedrine or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit
- •Taking anti-hypertensive medication for the treatment of hypertension. Anti-hypertensive medication taken at night to prevent supine hypertension will be allowed
- •Changing dose or frequency of PD medication within 2 weeks of baseline
- •Use of cognitive-enhancing medications (donepezil, galantamine, rivastigmine, tacrine, or memantine), catechol-O-methyltransferase inhibitors (tolcapone or entacapone), anticholinergic drugs, or antipsychotic drugs (including quetiapine or clozapine).
- •Known or suspected alcohol or substance abuse within 1 year (e.g. DSM-IV definition of alcoholism)
- •Past or current history of chronic severe hypertension (with repeated findings of BP 150/90 mmHg in the supine or standing position)
- •Symptomatic coronary artery disease, severe congestive heart failure (NYHA Class 3 or 4)
- •Unable to remain off any effective Freezing of Gait medications for 12 hrs prior to Evaluation visits)
- •Women who are pregnant, lactating, or plan to become pregnant during the course of this study
- •Women of child bearing potential who are not using two methods of contraception (at least one barrier, i.e. condom) with their partner.
- •Male subjects who are sexually active with a woman of child bearing potential and not using two methods of contraception (at least one barrier, for example, condom)
- •A history of closed angle glaucoma;
- •Active (in the last 6 months) atrial fibrillation or, in the investigator's opinion, any other significant cardiac arrhythmia that should preclude the subject from this trial
- •History of myocardial infarction or unstable angina
- •Congestive heart failure (NYHA Class 3 or 4)
- •Diabetes insipidus, insulin-dependent diabetes mellitus, or diabetic neuropathy
- •In the investigator's opinion, any other significant systemic illness
- •Known or suspected malignancy (other than basal cell carcinoma)
- •Known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug
- •Any major surgical procedure within 30 days of the baseline visit
- •Currently receiving any investigational drug or have received an investigational drug within 30 days of the baseline visit
- •In the investigator's opinion, clinically significant abnormalities on clinical examination or laboratory testing that should preclude the subject from this trial.
- •Findings from suicidality screening that are compatible with risk for suicide
研究组 & 干预措施
droxidopa, then sugar pill
Droxidopa will be titrated over a 2-week period up to 300 mg twice daily (600 mg total daily dose). Subjects will be titrated to highest tolerated dose and will continue on that dose for two weeks. Then, the subject will start sugar pills.
干预措施: Droxidopa (Drug)
droxidopa, then sugar pill
Droxidopa will be titrated over a 2-week period up to 300 mg twice daily (600 mg total daily dose). Subjects will be titrated to highest tolerated dose and will continue on that dose for two weeks. Then, the subject will start sugar pills.
干预措施: sugar pill (Drug)
sugar pill, then droxidopa
Subject will be be on sugar pill for 5 weeks (4 weeks of placebo treatment and one week of wash-out or sugar pills). Then, droxidopa will be titrated over 2 week period up to 300 mg twice daily (600 mg total daily dose). Subjects will be titrated to highest tolerated dose and will continue on that dose for two weeks.
干预措施: Droxidopa (Drug)
sugar pill, then droxidopa
Subject will be be on sugar pill for 5 weeks (4 weeks of placebo treatment and one week of wash-out or sugar pills). Then, droxidopa will be titrated over 2 week period up to 300 mg twice daily (600 mg total daily dose). Subjects will be titrated to highest tolerated dose and will continue on that dose for two weeks.
干预措施: sugar pill (Drug)
结局指标
主要结局
Change from baseline in freezing of gait symptoms using Freezing of Gait Questionnaire
时间窗: 4 weeks
Evaluate the effect of droxidopa on freezing of gait symptoms using the Freezing of Gait Questionnaire completed by patients. All measures will be performed at baseline and after two and four weeks of study medication.
Change from baseline in cognitive testing
时间窗: 4 weeks
Battery of cognitive testing is performed. All measures will be performed at baseline and after two and four weeks of study medication.
次要结局
- Change in measurement of freezing of gait(4 weeks)
- Change in the incidence of falls(4 weeks)
- Change in signs and symptoms of Parkinson's disease(4 weeks)
- Number of participants with serious and non-serious adverse events(up to 11 weeks)
研究者
Peter LeWitt MD
M.D.
Henry Ford Health System