Clinical trial NCT06564714: Early Pharmacological Treatment of Acute Spasticity After Spinal Cord Injury
Official title: Early Pharmacological Treatment of Acute Spasticity After Spinal Cord Injury to Promote Long-term Neurofunctional Recovery: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Traumatic Spinal Cord Injury
Keywords: Trauma
Spinal Cord Injury
Baclofen
Spasticity
Lead sponsor: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
Sponsor class: OTHER
First posted: 2024-08-21
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 55 recruited participants will be randomized into the early baclofen treatment group or the control group.
Primary purpose: TREATMENT

Brief summary: 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 :

1. Assess the safety of early baclofen treatment during acute care after SCI.
2. 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Spinal Cord Independence Measure (SCIM)
timeFrame: 6 months after the injury
measure: Adverse Events
timeFrame: From acute care to 6 months after the injury,
Secondary outcomes:
measure: Spastic reflexe assessment
timeFrame: All data on spastic reflexes will be collected from acute care to 6 months after the injury
measure: Muscle Spasticity assessment
timeFrame: All treatment and data on spasticity will be collected from acute care to 6 months after the injury.
measure: Spasticity frequency
timeFrame: All data on the frequency of spasticity will be collected from acute care to 6 months after the injury
measure: Spasticity impact
timeFrame: All data on the impact of spasticity will be collected from acute care to 6 months after the injury
measure: Neurological Assessment
timeFrame: From acute care to 6 months after the injury,
measure: Functional Assessment and Independent Walking
timeFrame: From acute care to 6 months after the injury,
measure: Pain Assessment
timeFrame: From acute care to 6 months after the injury
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: CIUSSS du Nord-de-l'île-de-Montréal-Hôpital du Sacré-Cœur de Montréal
state: Quebec
Study officials:
affiliation: CIUSSS du Nord-de-l'île-de-Montréal-Hôpital du Sacré-Cœur de Montréal
name: Andréane Richard-Denis, M.D., MSC
role: PRINCIPAL_INVESTIGATOR
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