Treatment of Lower Leg Anterolateral Chronic Exertional Compartment Syndrome With Intra-muscular Botulinum Injections.

Sponsor

University of Calgary (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05765071

Collaborator

Canadian Academy of Sport and Exercise Medicine (CASEM) (Other), Kinesis Medical Centre Inc. (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The goal of this pilot triple-blind randomized clinical trial is to determine the effectiveness of intra-muscular botulism injection for treatment of lower leg anterolateral chronic exertional compartment syndrome (CECS).

Primary Research Question: What is the effectiveness of intra-muscular botulinum injection, compared to normal saline placebo, for reducing pain related to painful sport activity in patients with lower leg anterolateral chronic exertional compartment syndrome (CECS), over a 24-week period?

Secondary outcomes will measure the time to initial onset and duration of pain during the painful sport activity, characterize the type of pain, foot paraesthesias, self-reported ankle instability, and ankle dorsiflexion and eversion muscle power. The Single Assessment Numeric Evaluation (SANE) score will provide a measure of overall leg function.

Adult patients with a confirmed diagnosis of anterolateral CECS, as determined by post-exertional compartment pressure measurements, will be invited to participate in the study. Using concealed, consecutively-numbered randomization envelopes, participants will be randomly assigned to receive either the botulinum (treatment) or the normal saline (control) injection. Participants will answer a web-based outcome questionnaire at Baseline (prior to receiving the injection) and at 2, 4, 6, 8, 12, 16, 24-weeks follow-up. Participants will be asked to do their painful sport activity the day before completing the questionnaire. Ankle dorsiflexion and eversion muscle power will be manually measured by a physiatrist in clinic at 6, 16 and 24-week follow-up visits.

Condition or Disease	Intervention/Treatment	Phase
Chronic Exertional Compartment Syndrome	Biological: Botulinum toxin A Biological: Normal saline	N/A

Detailed Description

Chronic exertional compartment syndrome (CECS) of the lower leg muscle compartments is a common problem in the active population. The condition often significantly restricts patients from participating in their desired activity to the best of their ability. The pathology of CECS is related to increased intra-muscular pressure related to a restrictive fascia (envelope around the muscle or muscle group). The current standard of care for definitive treatment of CECS is a surgical fasciotomy. However, there have been a number of case reports reporting successful reduction of the symptoms of CECS with intra-muscular botulinum injections. Intra-muscular botulinum injections may reduce the symptoms of CECS by potentially decreasing muscle activation, therefore diminishing blood flow, which may reduce intra-compartmental muscle expansion and pressure of the compartment during exercise. Thus botulinum injections might provide a non-operative method of treating CECS.

This study will determine the effectiveness of intra-muscular botulinum injection, compared to a normal saline placebo, for treatment of lower leg anterolateral CECS, over a 24-week period. Participants will answer a web-based questionnaire before receiving the injection (Baseline) and at regular follow-up intervals at 2, 4, 6, 8, 12, 16, 24-weeks post-injection. The questionnaires will ask the participant to provide detailed information about their painful sport activity, and the maximum level of pain that they experience during that activity. They will also characterize the type of pain experienced, record the time to initial onset and duration of pain during the painful sport activity, and provide an overall measure of their leg function using a Single Assessment Numeric Evaluation (SANE) score. Participants will also attend an in-person appointment in clinic at Baseline, and at 6, 16 and 24-weeks post-injection for assessment of numbness and/or tingling in the foot, ankle instability, and manual ankle muscle power.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants receiving botulinum toxin will be compared to those receiving normal saline.Participants receiving botulinum toxin will be compared to those receiving normal saline.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Participants will be blinded to the treatment they received until after the 24-week visit is completed. The physiatrist administering the injection and the physiatrist performing the manual muscle power assessments will be blinded to treatment allocation.

Primary Purpose:

Treatment

Official Title:

Treatment of Lower Leg Anterolateral Chronic Exertional Compartment Syndrome With Intra-muscular Botulinum Injections.

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment Botulinum toxin (Botox) injection	Biological: Botulinum toxin A Botulinum injections will be prepared by diluting 100 units of botulinum toxin A with 5.0mL of saline (20.0U/mL). A total of 100 units (5.0mL) of botulinum toxin A will be injected into the tibialis anterior, peroneus longus and peroneus brevis muscles of the affected leg. Under ultrasound guidance, the injectant will be deposited at two sites in each muscle near the motor points. Other Names: Botox
Placebo Comparator: Control Normal saline injection	Biological: Normal saline A total of 5.0mL of normal saline will be injected into the tibialis anterior, peroneus longus and peroneus brevis muscles of the affected leg. Under ultrasound guidance, the injectant will be deposited at two sites in each muscle near the motor points. Other Names: Placebo

Arm

Intervention/Treatment

Active Comparator: Treatment

Botulinum toxin (Botox) injection

Biological: Botulinum toxin A

Botulinum injections will be prepared by diluting 100 units of botulinum toxin A with 5.0mL of saline (20.0U/mL). A total of 100 units (5.0mL) of botulinum toxin A will be injected into the tibialis anterior, peroneus longus and peroneus brevis muscles of the affected leg. Under ultrasound guidance, the injectant will be deposited at two sites in each muscle near the motor points.

Other Names:

Botox

Placebo Comparator: Control

Normal saline injection

Biological: Normal saline

A total of 5.0mL of normal saline will be injected into the tibialis anterior, peroneus longus and peroneus brevis muscles of the affected leg. Under ultrasound guidance, the injectant will be deposited at two sites in each muscle near the motor points.

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures

Change in maximum level of pain at time of painful sport activity from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection [Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection]
Pain measured on a visual analog scale from 0 to 100, where 0 represents no pain and 100 represents pain as bad as it can be

Secondary Outcome Measures

Change in time to onset of pain during sport activity (minutes) [Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection]
Comparison of time to onset of pain during sport activity (minutes) at Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Change in duration of exercise before having to stop due to pain (minutes) [Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection]
Comparison of duration of exercise before having to stop due to pain (minutes) at Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Change in duration of pain after stopping painful exercises (minutes) [Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection]
Comparison of duration of pain after stopping painful exercises (minutes) at Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Change in the numbness and/or tingling in foot during painful exercises from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection [Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection]
Presence or absence of numbness and/or tingling in foot during painful exercises
Change in ankle dorsiflexion muscle power from Baseline to 6, 16 and 24-weeks post-injection [Baseline, and 6, 16 and 24-weeks post-injection]
Manual ankle dorsiflexion muscle power test, graded on the following scale: 0 No muscle activation Flicker of contraction, but no movement of the ankle joint Dorsiflexion of the foot with the effect of gravity eliminated Dorsiflexion of the foot against gravity but no added resistance Dorsiflexion of the foot against gravity and moderate resistance Dorsiflexion of the foot against gravity and full resistance
Ankle eversion muscle power [Baseline, and 6, 16 and 24-weeks post-injection]
Manual ankle eversion muscle power test, graded on the following scale: 0 No muscle activation Flicker of contraction, but no movement of the ankle joint Eversion of the foot with the effect of gravity eliminated Eversion of the foot against gravity but no added resistance Eversion of the foot against gravity and moderate resistance Eversion of the foot against gravity and full resistance
Change in Single Assessment Numeric Evaluation (SANE) from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection [Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection]
Comparison from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection for self-assessed rating of overall leg function using a Visual Analog Scale response, where 0 is severely abnormal and 100 is completely normal.
Change in ankle instability from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection [Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection]
Change in patient-reported assessment of presence or absence of ankle instability from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed diagnosis of lower leg anterolateral chronic exertional compartment syndrome (CECS), as measured post-exertional compartment pressure measurements of greater than 30 mmHg for immediate post-exertional compartment pressure, and greater than 12 mmHg at 5 minutes after stopping exercise.

Exclusion Criteria:

Female patients who are pregnant, trying to get pregnant or lactating
History of keloidal scarring
History of any significant neurologic disease (ie: amyotrophic lateral sclerosis, motor neuropathy, myasthenia gravis, Lambert-Eaton syndrome)