Early Pharmacological Treatment of Acute Spasticity After Spinal Cord Injury

August 19, 2024 updated by: Andréane Richard-Denis, Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

Early Pharmacological Treatment of Acute Spasticity After Spinal Cord Injury to Promote Long-term Neurofunctional Recovery: a Randomized Clinical Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

55

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Quebec
      • Montréal, Quebec, Canada, H4J 1C5
        • CIUSSS du Nord-de-l'île-de-Montréal-Hôpital du Sacré-Cœur de Montréal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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,
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.
Other: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Spinal Cord Independence Measure (SCIM)
Time Frame: 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.
6 months after the injury
Adverse Events
Time Frame: 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.
From acute care to 6 months after the injury,

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Spastic reflexe assessment
Time Frame: All data on spastic reflexes will be collected from acute care to 6 months after the injury

The Spinal Cord Assessment Tool for Spastic Reflexes (SCATS) will be used to measure spastic reflexes. This will be measured weekly, after hospital discharge and during outpatient follow-up visits 6 weeks and 6 months after the injury.

The SCATS is split into 3 subscales, each addressing a seperate spasm.

1) Clonus 2) Flexor spasms 3) Extensor spasms.

For each subscale, the spasm is triggered and then rated. The degree of spasm is rated between 0 (no spasm) to 3 (severe spasm lasting longer than 10 seconds)
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.

The Modified Ashworth Scale (MAS) will be used to measure spasticity for each muscle assessed.

The MAS is a 6-point scale. Scores range from 0 (no increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension). This scale also adds a +1 scoring category to indicate resistance through less than half of the movement.

Lower scores represent normal muscle tone and higher scores represent spasticity.
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

The Modified Penn Spasm Frequency Scale (mPSFS) will be used to quantify spasticity.

It is a 2 component self-report measure in which the patients will report their perception of spasticity in regards to frequency and severity.

The first component is a 5 point scale assessing the frequency with which spasms occur ranging from 0 (No spasms) to 4 (Spontaneous spasms occurring more than ten times per hour)

The second component is a 3 point scale assessing the severity of spasms ranging from 1 (Mild) to 3 (Severe).

The second component is not answered if the person indicates they have no spasms in part 1.
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

The Patient Reported Impact of Spasticity Measure (PRISM) measures the impact of SCI-related spasticity on quality of life from the patient's perspective.

The PRISM consists of 41 items, divided into 7 subscales namely anxiety, psychological agitation, daily activities, assistance, positive impact, need for intervention, social embarrassment.

It uses 5 point Likert Scale for scoring, 0 = Never true for me, 1 = Rarely true for me, 3 = Often true for me, 4 = Very often true for me. A higher score is considered unhealthy.
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,

The neurological status assessed from repeated neurological examinations between baseline and 6 months post-SCI will be measured using the International Standards for Neurological Classification of SCI (ISNCSCI)

This impairment scale involves both a motor and sensory examination to determine the sensory and motor levels for the right and left side, the overall neurological level of the injury and completeness of the injury (i.e. whether the injury is complete or incomplete).

Sensory evaluation is completed using a three-point scale for scoring. 0 = absent, 1 = altered (impaired or partial appreciation, including hyperesthesia), 2 = normal or intact (similar as on the cheek), NT = not testable.

Motor evaluation is completed using a six-point scale for scoring ranging from 0 (total paralysis) to 5 (normal) active movement, full range of motion against gravity and full resistance in a muscle specific position expected from an otherwise unimpaired person)
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,

The 3rd version of the Spinal Cord Independence Measure (SCIM) will be used to report the ability of SCI patients to perform daily living activities independently,

This questionnaire will measure Functional outcome of SCI partients before acute care and inpatient rehabilitation discharge, and at each follow-up visit.
From acute care to 6 months after the injury,
Pain Assessment
Time Frame: From acute care to 6 months after the injury

Pain assessment will be measured using the International Spinal Cord Injury Pain Basic Data Set (version 2.0).

Information concerning pain's interference with physical and emotional function and sleep, probable pain diagnosis, pain location, pain intensity, and duration will be collected.
From acute care to 6 months after the injury

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Investigators

  • Principal Investigator: Andréane Richard-Denis, M.D., MSC, CIUSSS du Nord-de-l'île-de-Montréal-Hôpital du Sacré-Cœur de Montréal

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2024

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

June 1, 2029

Study Registration Dates

First Submitted

January 30, 2024

First Submitted That Met QC Criteria

August 19, 2024

First Posted (Actual)

August 21, 2024

Study Record Updates

Last Update Posted (Actual)

August 21, 2024

Last Update Submitted That Met QC Criteria

August 19, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MP-32-2023-2550

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Traumatic Spinal Cord Injury

Clinical Trials on Early baclofen Intervention

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Oman

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe