The CAMAROS Trial: The Canadian Maraviroc Randomized Controlled Trial To Augment Rehabilitation Outcomes After Stroke
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 6
- 主要终点
- Change in Fugl-Meyer Upper Extremity Assessment Score
研究概览
简要总结
The CAMAROS trial is a randomized controlled phase II trial analyzing the effect of coupling a C-C chemokine receptor 5 (CCR5) antagonist, Maraviroc (Celsentri), and exercise to improve both upper and lower extremity recovery after a stroke.
详细描述
After stroke, the combination of progressive skills practice in an adequate dose plus exercise for fitness augments motor and cognitive outcomes. However, sensorimotor and cognitive improvements often plateau after 12 weeks. There is an urgent need to find novel methods to drive recovery and lessen limb paralysis. Drugs that might enhance learning or neural repair, as well as other molecular and synaptic adaptations that occur during skills training and fitness exercise, might extend that recovery curve, although to date only fluoxetine has given any hint of this. Most trials have tested agents that modulate neurotransmitters. Several very recent preclinical experiments and observational studies in patients after stroke suggest that the commercially available medication, Maraviroc, may augment skills learning during rehabilitation training especially during the first three months after onset, by acting on unique molecular components for novel learning.
The CAMAROS trial is a randomized, placebo-controlled, blinded phase II trial evaluating the efficacy of coupling Maraviroc (Celsentri) with exercise rehabilitation across multiple Canadian sites in 120 stroke participants. Patients will begin their participation within 8 weeks of stroke onset. Both groups will receive an exercise program in addition to standard of care rehabilitation, but only one group (the intervention group) will receive the active drug Maraviroc.
Study participants will be evaluated using physical assessments, cognitive assessments, and using wrist and ankle activity sensors at baseline, after 4 weeks of taking the drug/placebo, after 8 weeks of taking the drug/placebo, and at 6-months post-stroke. While enrolled in the study, participants will be required to take part in an 8 week, daily exercise program. Participants will also perform a short motor learning assessment at each formal assessment and again within 72 hours of each formal assessment (initial test and retention test).
Evaluators and participants will be blind to the treatment administered. The trial is constructed with randomization to remove selection and allocation biases and to ensure greater validity in observed differences in the outcome measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary ischemic anterior circulation stroke
- •Age ≥18 years
- •At least 5 days after stroke but within 8 weeks of stroke on the date of medication (maraviroc or placebo) start
- •Hemiparesis requiring inpatient rehabilitation
- •Assistance available for daily rehabilitation training practice and for transportation when needed
- •Adequate language skills to understand the Informed Consent and retain information during daily therapies
- •At least one of the following:
- •some shoulder abduction with gravity eliminated and visible extension in two or more digits OR
- •visible hip flexion or extension
- •Subgroup Stratification Criteria
- •For Upper Extremity Group:
- •Minimum Ability: Medical Research Council (MRC) grade >1 for shoulder abduction AND MRC grade >1 for finger extensor on at least two digits
- •Maximum Ability: Upper Extremity Fugl-Meyer Assessment Score >56
- •For Lower Extremity Group:
- •Minimum Ability: requiring a 2-person assist
- •Maximum Ability: walking speed <0.8m/s
排除标准
- •Pre-stroke modified Rankin score ≥ 2
- •Limited resources or illness that will not enable a return to living outside of a facility
- •History of dementia
- •History of hepatitis or elevated hepatic transaminases or bilirubin
- •History of renal insufficiency or creatinine clearance (eGFR) < 60mL / min / 1.73m2
- •Cancer or other chronic illness that makes 1-year survival unlikely or will detract from the ability to carry out exercise and skills practice
- •Existing pre-stroke serious disabling disease (e.g., Parkinson's disease, severe traumatic brain injury, amputation)
- •Seizure related to stroke
- •Acute or chronic epilepsy
- •Currently taking any of the following anticonvulsant medications:
- •Carbamazepine
- •Phenobarbital
- •Phenytoin
- •Pregnant, breastfeeding, or positive test for pregnancy at baseline
- •Women of childbearing potential who are not using one highly effective form of contraception or two forms of effective contraception
- •Known HIV positivity
- •Currently taking any of the following antifungal and/or antibacterial medications:
- •Ketoconazole
- •Itraconazole
- •Voriconazole
- •Clarithromycin
- •Rifabutin + Protease Inhibitor
- •Currently taking St. John's Wort
- •Currently taking Paxlovid
研究组 & 干预措施
Maraviroc (Celsentri)
Maraviroc (Celsentri) will be administered to this group. Participants will be administered a dose of 300mg to be taken twice per day for the duration of the exercise intervention (8 weeks).
干预措施: Maraviroc (Drug)
Placebo
An over-encapsulated placebo, or "sugar pill" (so it appears identical to the trial drug) will be administered to this group. Participants will be administered the placebo identical to the 300mg maraviroc tablet for the duration of the exercise intervention (8 weeks).
干预措施: Placebo (Other)
Maraviroc (Celsentri)
Maraviroc (Celsentri) will be administered to this group. Participants will be administered a dose of 300mg to be taken twice per day for the duration of the exercise intervention (8 weeks).
干预措施: Exercise Program (Behavioral)
Maraviroc (Celsentri)
Maraviroc (Celsentri) will be administered to this group. Participants will be administered a dose of 300mg to be taken twice per day for the duration of the exercise intervention (8 weeks).
干预措施: Activity Sensor (Device)
Maraviroc (Celsentri)
Maraviroc (Celsentri) will be administered to this group. Participants will be administered a dose of 300mg to be taken twice per day for the duration of the exercise intervention (8 weeks).
干预措施: Motor Learning (Behavioral)
Placebo
An over-encapsulated placebo, or "sugar pill" (so it appears identical to the trial drug) will be administered to this group. Participants will be administered the placebo identical to the 300mg maraviroc tablet for the duration of the exercise intervention (8 weeks).
干预措施: Exercise Program (Behavioral)
Placebo
An over-encapsulated placebo, or "sugar pill" (so it appears identical to the trial drug) will be administered to this group. Participants will be administered the placebo identical to the 300mg maraviroc tablet for the duration of the exercise intervention (8 weeks).
干预措施: Activity Sensor (Device)
Placebo
An over-encapsulated placebo, or "sugar pill" (so it appears identical to the trial drug) will be administered to this group. Participants will be administered the placebo identical to the 300mg maraviroc tablet for the duration of the exercise intervention (8 weeks).
干预措施: Motor Learning (Behavioral)
结局指标
主要结局
Change in Fugl-Meyer Upper Extremity Assessment Score
时间窗: Baseline (between 5 days and 8 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke
Difference in subscale scores on the Upper-Extremity Fugl-Meyer Assessment - both motor (max 66) and sensory (max 12) components. Higher scores indicate better outcome.
Change in 10-Meter Walk Test Score
时间窗: Baseline (between 5 days and 8 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke
A performance measure used to assess walking speed in meters per second over a short distance. It can be used to determine functional mobility, gait, and vestibular function. Faster speed indicates better function.
次要结局
- Action Research Arm Test (ARAT)(Baseline (between 5 days and 8 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke)
- 6 Minute Walk Test(Baseline (between 5 days and 8 weeks after stroke), after 4 weeks on drug/placebo, after 8 weeks on drug/placebo, and 6-months post-stroke)