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

Overview

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.

Interventions

• Drug Early baclofen Intervention
  Baclofen is initiated as soon as any sign of acute spasticity. 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.
• Drug Usual routine care
  Baclofen is initiated only when acute spasticity is deemed problematic. 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.

Primary outcome measures

• Spinal Cord Independence Measure (SCIM) [Time frame: 6 months after the injury]
• Adverse Events [Time frame: From acute care to 6 months after the injury,]

Secondary outcome measures (7)

• Spastic reflexe assessment [Time frame: All data on spastic reflexes will be collected from acute care to 6 months after the injury]
• Muscle Spasticity assessment [Time frame: All treatment and data on spasticity will be collected from acute care to 6 months after the injury.]
• Spasticity frequency [Time frame: All data on the frequency of spasticity will be collected from acute care to 6 months after the injury]
• Spasticity impact [Time frame: All data on the impact of spasticity will be collected from acute care to 6 months after the injury]
• Neurological Assessment [Time frame: From acute care to 6 months after the injury,]
• Functional Assessment and Independent Walking [Time frame: From acute care to 6 months after the injury,]
• Pain Assessment [Time frame: From acute care to 6 months after the injury]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• CIUSSS du Nord-de-l'île-de-Montréal-Hôpital du Sacré-Cœur de Montréal — Montreal

Publications

• Cragg JJ, Tong B, Jutzeler CR, Warner FM, Cashman N, Geisler F, Kramer JLK. A Longitudinal Study of the Neurologic Safety of Acute Baclofen Use After Spinal Cord Injury. Neurotherapeutics. 2019 Jul;16(3):858-867. doi: 10.1007/s13311-019-00713-8. PMID 30725362
• Pandyan AD, Gregoric M, Barnes MP, Wood D, Van Wijck F, Burridge J, Hermens H, Johnson GR. Spasticity: clinical perceptions, neurological realities and meaningful measurement. Disabil Rehabil. 2005 Jan 7-21;27(1-2):2-6. doi: 10.1080/09638280400014576. No abstract available. PMID 15799140
• Adams MM, Hicks AL. Spasticity after spinal cord injury. Spinal Cord. 2005 Oct;43(10):577-86. doi: 10.1038/sj.sc.3101757. PMID 15838527
• Holtz KA, Lipson R, Noonan VK, Kwon BK, Mills PB. Prevalence and Effect of Problematic Spasticity After Traumatic Spinal Cord Injury. Arch Phys Med Rehabil. 2017 Jun;98(6):1132-1138. doi: 10.1016/j.apmr.2016.09.124. Epub 2016 Oct 22. PMID 27780743
• Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, Fehlings MG. Traumatic spinal cord injury. Nat Rev Dis Primers. 2017 Apr 27;3:17018. doi: 10.1038/nrdp.2017.18. PMID 28447605
• Ayoub S, Smith JG, Cary I, Dalton C, Pinto A, Ward C, Saverino A. The positive and the negative impacts of spasticity in patients with long-term neurological conditions: an observational study. Disabil Rehabil. 2021 Nov;43(23):3357-3364. doi: 10.1080/09638288.2020.1742803. Epub 2020 Mar 30. PMID 32223455
• Ehrmann C, Mahmoudi SM, Prodinger B, Kiekens C, Ertzgaard P. Impact of spasticity on functioning in spinal cord injury: an application of graphical modelling. J Rehabil Med. 2020 Mar 31;52(3):jrm00037. doi: 10.2340/16501977-2657. PMID 32103278
• D'Amico JM, Condliffe EG, Martins KJ, Bennett DJ, Gorassini MA. Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity. Front Integr Neurosci. 2014 May 12;8:36. doi: 10.3389/fnint.2014.00036. eCollection 2014. PMID 24860447

Identifiers

NCT: NCT06564714 · MP-32-2023-2550

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗