Early Pharmacological Treatment of Acute Spasticity After Spinal Cord Injury

NCT ID: NCT06564714

Last Updated: 2024-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-31

Study Completion Date

2029-06-30

Brief Summary

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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

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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.

Conditions

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Traumatic Spinal Cord Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

55 recruited participants will be randomized into the early baclofen treatment group or the control group.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

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.

Study Groups

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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,

Group Type EXPERIMENTAL

Early baclofen Intervention

Intervention Type DRUG

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.

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.

Group Type OTHER

Usual routine care

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

OTHER

Sponsor Role lead

Responsible Party

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Andréane Richard-Denis

Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Andréane Richard-Denis, M.D., MSC

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Montreal, Quebec, Canada

Site Status

Countries

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Canada

Central Contacts

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Lara Chawa

Role: CONTACT

514-338-2222 ext. 5833276

Pascal Mputu

Role: CONTACT

514-338-2222 ext. 5833270

References

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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.

Reference Type BACKGROUND
PMID: 30725362 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15799140 (View on PubMed)

Adams MM, Hicks AL. Spasticity after spinal cord injury. Spinal Cord. 2005 Oct;43(10):577-86. doi: 10.1038/sj.sc.3101757.

Reference Type BACKGROUND
PMID: 15838527 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27780743 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28447605 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32223455 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32103278 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24860447 (View on PubMed)

Bhimani RH, Anderson LC, Henly SJ, Stoddard SA. Clinical measurement of limb spasticity in adults: state of the science. J Neurosci Nurs. 2011 Apr;43(2):104-15. doi: 10.1097/jnn.0b013e31820b5f9f.

Reference Type BACKGROUND
PMID: 21488584 (View on PubMed)

Adams MM, Ginis KA, Hicks AL. The spinal cord injury spasticity evaluation tool: development and evaluation. Arch Phys Med Rehabil. 2007 Sep;88(9):1185-92. doi: 10.1016/j.apmr.2007.06.012.

Reference Type BACKGROUND
PMID: 17826466 (View on PubMed)

Lechner HE, Frotzler A, Eser P. Relationship between self- and clinically rated spasticity in spinal cord injury. Arch Phys Med Rehabil. 2006 Jan;87(1):15-9. doi: 10.1016/j.apmr.2005.07.312.

Reference Type BACKGROUND
PMID: 16401432 (View on PubMed)

Levasseur A, Mac-Thiong JM, Richard-Denis A. Are early clinical manifestations of spasticity associated with long-term functional outcome following spinal cord injury? A retrospective study. Spinal Cord. 2021 Aug;59(8):910-916. doi: 10.1038/s41393-021-00661-1. Epub 2021 Jul 6.

Reference Type BACKGROUND
PMID: 34230603 (View on PubMed)

Hiersemenzel LP, Curt A, Dietz V. From spinal shock to spasticity: neuronal adaptations to a spinal cord injury. Neurology. 2000 Apr 25;54(8):1574-82. doi: 10.1212/wnl.54.8.1574.

Reference Type BACKGROUND
PMID: 10762496 (View on PubMed)

Dietz V, Sinkjaer T. Spastic movement disorder: impaired reflex function and altered muscle mechanics. Lancet Neurol. 2007 Aug;6(8):725-33. doi: 10.1016/S1474-4422(07)70193-X.

Reference Type BACKGROUND
PMID: 17638613 (View on PubMed)

Li S, Francisco GE, Rymer WZ. A New Definition of Poststroke Spasticity and the Interference of Spasticity With Motor Recovery From Acute to Chronic Stages. Neurorehabil Neural Repair. 2021 Jul;35(7):601-610. doi: 10.1177/15459683211011214. Epub 2021 May 12.

Reference Type BACKGROUND
PMID: 33978513 (View on PubMed)

Other Identifiers

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MP-32-2023-2550

Identifier Type: -

Identifier Source: org_study_id

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