Early Pharmacological Treatment of Acute Spasticity After Spinal Cord Injury to Promote Long-term Neurofunctional Recovery: a Randomized Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Spinal Cord Independence Measure (SCIM)
研究概览
简要总结
The objective of this clinical trial is to evaluate if early detection of spasticity and immediate treatment with oral baclofen during acute care prevents problematic spasticity and improves neurofunctional recovery after tSCI.
The main questions it aims to answer are :
- Assess the safety of early baclofen treatment during acute care after SCI.
- Compare the neurofunctional outcomes between the early baclofen group and the control group up to 6 months after tSCI, in terms of mobility, global functional independence, neurological recovery, pain and spasticity.
The early baclofen group will receive oral administration of baclofen as soon as any sign of acute spasticity is observed. The dose is started initially at 5 mg three times a day and is increased every 7 days by 5 mg per intake (up to a maximum 80 mg total per day) until achieving an optimal response, i.e. when spasticity is no longer problematic. The control group however will receive the "usual routine care" at our institution as per which baclofen is initiated by the attending physician (i.e. physiatrist or spine surgeon) only when acute spasticity becomes severe and problematic.
详细描述
Spasticity is a condition in which muscles are abnormally stiff or tight, and interfere with normal movement. Following spinal cord injury (SCI), spasticity is common, affecting up to 70% of patients in the chronic stage 6 months or more after the injury. (1-4). After SCI, spasticity is due to a stretch reflex disorder of sensorimotor control following an upper motor neuron lesion, i.e. a lesion involving the neurons carrying the information within the spinal cord. Clinically, spasticity manifests as a complex syndrome of velocity-dependent hypertonia, clonus (rhythmic oscillating stretch reflex) and spasms (involuntary muscle contractions) that can have profound consequences on function and quality of life.
Traditionally, the clinical impact of spasticity has been mostly recognized during the subacute and chronic phases after SCI. Based upon the current management paradigm, the great majority of individuals with spasticity will receive pharmaceutical treatment for spasticity only during the rehabilitation period weeks or months after the injury when the clinical manifestations become severe and problematic. The investigators have challenged this long-held belief by proposing their paradigm shift towards early recognition and treatment of spasticity during the acute within the first month after SCI, after showing that about half of individuals will develop clinical signs of early spasticity during the acute hospitalization, and that acute spasticity is associated with poor long-term outcomes.
In particular, the investigators found that long-term mobility is significantly decreased in individuals presenting acute spasticity within the first month after the SCI. Our preliminary data suggest that prompt pharmacological treatment with baclofen - an anti-spasmodic medication - during the acute hospitalization improves neurological recovery in the presence of acute spasticity. Based on these preliminary findings, the overarching hypothesis of this study is that long-term neurofunctional outcomes are improved by early detection of acute spasticity and immediate treatment with oral baclofen.
Our team of experienced clinician-scientists specialized in SCI care therefore propose a single-site pilot randomized clinical trial including 55 patients admitted for a traumatic SCI (tSCI), in order to evaluate the safety and neurofunctional benefits of early baclofen treatment (i.e. as soon as any signs of spasticity are observed within the first month after the injury) during the acute hospitalization.
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
- None
盲法说明
Both investigators and trial participants will be fully aware of which treatment group the participants are in and what treatments are assigned to them.
Participants will be randomized into the early baclofen treatment or control group using computer-generated random treatment assignment.
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
- •Male or female aged 18 years or older
- •Blunt (non-penetrating) traumatic SCI
- •AIS grade A to D
- •NLI between C0 and L1
- •Patient willing and able to provide informed consent
排除标准
- •Non-traumatic SCI (e.g. tumor, infection, transverse myelitis, etc.)
- •AIS grade E upon admission
- •Penetrating tSCI (from stab wound, gunshot injury, etc.)
- •Cauda equina syndrome or NLI below L1
- •Moderate or severe brain injury (mild traumatic brain injury not an exclusion criteria)
- •Contraindication to oral baclofen use (needs clearance from attending physician and pharmacological consultant)
- •Pre-existing neurological disorders (cerebrovascular disease, Parkinson's disease, multiple sclerosis, etc.)
- •Major cognitive deficits precluding informed consent and/or assessments
- •Unlikely to comply with scheduled visits (e.g. living in another country)
- •Renal insufficiency
研究组 & 干预措施
Early Baclofen treatment group
Oral baclofen will be started as soon as any sign of acute spasticity consisting of spasms, velocity-dependent hypertonia and/or clonus is observed. Oral baclofen will be initiated the same day as when signs of spasticity are first observed.
Dosage : oral administration of baclofen is started initially at 5 mg three times a day. The dose is increased every 7 days by 5 mg per intake (up to a maximum 80 mg total per day) until achieving an optimal response,
干预措施: Early baclofen Intervention (Drug)
Control group
The control group will receive the "usual routine care" as per which baclofen is prescribed only when acute spasticity becomes severe and problematic.
In the presence of problematic spasticity, oral administration of baclofen is started initially at 5 mg three times a day. The dose is increased every 7 days by 5 mg per intake (up to a maximum 80 mg total per day) until achieving an optimal response.
干预措施: Usual routine care (Drug)
结局指标
主要结局
Spinal Cord Independence Measure (SCIM)
时间窗: 6 months after the injury
The primary outcome consists of the mobility subscore from the SCIM 6 months after the SCI with early baclofen treatment when compared to the control group. The SCIM will measure the ability of the 55 SCI patients to perform basic activities of daily living independently. There are 19 items divided into 3 subscales. A total score out of 100 is achieved, with the subscales weighted as follows: 1. self-care: scored 0-20; 2. respiration and sphincter management: scored 0-40; and 3. mobility: scored 0-40 Scores are higher in patients that require less assistance or fewer aids to complete basic activities of daily living and life support activities.
Adverse Events
时间窗: From acute care to 6 months after the injury,
Adverse events will be collected for both early baclofen treatment and control groups during acute care after SCI.
次要结局
- Muscle Spasticity assessment(All treatment and data on spasticity will be collected from acute care to 6 months after the injury.)
- Spasticity impact(All data on the impact of spasticity will be collected from acute care to 6 months after the injury)
- Neurological Assessment(From acute care to 6 months after the injury,)
- Spasticity frequency(All data on the frequency of spasticity will be collected from acute care to 6 months after the injury)
- Spastic reflexe assessment(All data on spastic reflexes will be collected from acute care to 6 months after the injury)
- Functional Assessment and Independent Walking(From acute care to 6 months after the injury,)
- Pain Assessment(From acute care to 6 months after the injury)
研究者
Andréane Richard-Denis
Principal investigator
Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal