Botox for the Treatment of Recurrent Chronic Exertional Compartment Syndrome

Phase 4

Terminated

Conditions: Compartment Syndrome of Leg

Interventions: Drug: Botox

Registration Number: NCT05006417

Lead Sponsor: University of Wisconsin, Madison

Brief Summary: 10 participants with Recurrent Chronic Exertional Compartment Syndrome (R-CECS) will be enrolled in a 6 month study at the University of Wisconsin Hospitals and Clinics to test the hypothesis that injection of Botox into the affected muscle group will alleviate pain associated with R-CECS.

Detailed Description: Participants will be enrolled in study at initial clinic visit by study staff at which time diagnosis of R-CECS will be established based on elevated pressure measurements in patients who have had surgical release of the affected compartments. Pressure testing will be performed outside of the clinical study and will be required to establish the diagnosis of R-CECS.

Initial clinic visit with study staff will consist of baseline measurements of ankle plantarflexion, dorsiflexion, inversion, and eversion strength using Kiio Force Sensor. The clinic visit with study staff will establish time point 0 and will consist of written consent for participation, Botox injection, and baseline University of Wisconsin Running Index (UWRI). Two months following this visit, the participant will have follow up with study staff. Study staff will again measure ankle strength (ankle inversion, eversion, plantarflexion, and dorsiflexion) using the Kiio Force Sensor utilizing the same strength assessment protocol. Study staff will monitor for side effects and administer the UWRI. Telephone follow up assessment of the UWRI will be made by study staff at 4 and 6 months.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

Willing to provide written informed consent
Willing to comply with all study procedures and be available for the duration of the study
Documented diagnosis of R-CECS determined with elevated compartmental pressure testing following lower extremity fascia release (fasciotomy or fasciectomy)
Females of childbearing potential must have a negative urine pregnancy test prior to enrollment and agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to randomization, for the duration of study participation, and for 7 days following completion of therapy.
- A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  - Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

Exclusion Criteria

History of hypersensitivity or allergy to any of the study drugs or drugs of similar chemical classes
Known neuromuscular disease
Known pulmonary disease including but not limited to asthma, pneumonia, or upper respiratory tract infection
Dysphagia
Known cardiac disease including but not limited to congestive heart failure, arrhythmia, or history of myocardial infarction
Enrolled in another clinical trial or has used of any investigational drugs, biologics, or devices within 30 days prior to enrollment
Currently or have taken in the past medications that affect neuromuscular function, aminoglycosides, muscle relaxants, or other botulinum neurotoxin agents. Currently taking any blood-thinning medications including, but not limited to Plavix, Coumadin, Eliquis, Xarelto
Women who are pregnant or breast-feeding
Vulnerable populations
Not suitable for study participation due to other reasons at the discretion of the investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants with R-CECS	Botox	Botox to be injected under standard palpatory technique into the affected lower leg compartment.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Lower Extremity Weakness	up to 6 months	A primary safety endpoint is incidence of lower extremity weakness, measured by
Incidence of Adverse Events	one study visit (within 2 hours)	A primary safety endpoint is the incidence of adverse events, such as bruising, bleeding, pain, redness, or swelling where the injection was given.
Change in Pain Score	2 months, 4 months, 6 months	Change in pain score (0-10, where 10 is increased pain) will be assessed at each time point will be assessed at each time point (2, 4, 6 months) using Friedman's ANOVA.

Secondary Outcome Measures

Name	Time	Method
Participant Frustration With Injury	baseline, 2 months, 4 months, 6 months	A question on the UWRI asks the participant to indicate how frustrated they are by their running injury. The scoring is on a 5 point likert scale from 0 = extremely frustrated, 1 = significantly frustrated, 2 = moderately frustrated, 3 = mildly frustrated, to 4 = not frustrated.
Change in Running Duration: Longest Run	baseline, 2 months, 4 months, 6 months	A question on the UWRI asks the participant to indicate if the distance of their longest weekly run has changed as a result of their injury. The scoring is on a 5 point likert scale from 0 = unable to run, 1 = significantly reduced, 2 = moderately reduced, 3 = minimally reduced, to 4 = same or longer than before my injury.
Change in Running Speed	baseline, 2 months, 4 months, 6 months	A question on the UWRI asks the participant to indicate if the distance of their longest weekly run has changed as a result of their injury. The scoring is on a 5 point likert scale from 0 = unable to run, 1 = significantly reduced, 2 = moderately reduced, 3 = minimally reduced, to 4 = same or longer than before my injury.
Participant Confidence in Increasing the Duration and Intensity of Running	baseline, 2 months, 4 months, 6 months	A question on the UWRI asks the participant to indicate how their injury affects their confidence to increase the duration or intensity of their running. The scoring is on a 5 point likert scale from 0 = I cannot increase my running, 1 = if I increase, I might get worse, 2 = neutral, 3 = if I increase I might be fine, to 4 = confident to increase my running.
Change in Ability to Perform Activities of Daily Living	baseline, 2 months, 4 months, 6 months	A question on the University of Wisconsin Running Index (UWRI) asks the participant to indicate how their running injury impacts their ability to perform daily activities. The scoring is on a 5 point likert scale from 0 = unable to perform, 1 = significantly impact, 2 = moderately impact, 3 = slightly impact, to 4 = no impact.
Participant Perception of Recovery From Injury	baseline, 2 months, 4 months, 6 months	A question on the UWRI asks the participant to indicate how much recovery have they made from their running injury. The scoring is on a 5 point likert scale from 0 = no recovery, 1 = minimal recovery, 2 = moderate recovery, 3 = significant recovery, to 4 = complete recovery.
Change in Ankle Dorsiflexion Strength Using Kiio Force Sensor	baseline and month 2	A Kiio Force Sensor will be used to measure the change in ankle strength. Change in strength outcomes at baseline and 2 months will be assessed using Wilcoxon signed rank tests or, if necessary, linear mixed effects models for repeated measures, to account for intra-subject correlation (left and right legs).
Change in Ankle Inversion Strength Using Kiio Force Sensor	baseline and month 2	A Kiio Force Sensor will be used to measure the change in ankle strength. Change in strength outcomes at baseline and 2 months will be assessed using Wilcoxon signed rank tests or, if necessary, linear mixed effects models for repeated measures, to account for intra-subject correlation (left and right legs).
Pain in the 24 Hours Following Running	baseline, 2 months, 4 months, 6 months	A question on the UWRI asks the participant to indicate how much pain they experience during the 24 hours following a run. The scoring is on a 5 point likert scale from 0 = unable to run, 1 = significant pain, 2 = moderate pain, 3 = minimal pain, to 4 = no pain.
Change in Running Duration: Weekly	baseline, 2 months, 4 months, 6 months	A question on the UWRI asks the participant to indicate if their weekly mileage or weekly running time changed as a result of their injury. The scoring is on a 5 point likert scale from 0 = unable to run, 1 = significantly reduced, 2 = moderately reduced, 3 = minimally reduced, to 4 = same or greater than before my injury.
Change in Ankle Plantarflexion Strength Using Kiio Force Sensor	baseline and month 2	A Kiio Force Sensor will be used to measure the change in ankle strength. Change in strength outcomes at baseline and 2 months will be assessed using Wilcoxon signed rank tests or, if necessary, linear mixed effects models for repeated measures, to account for intra-subject correlation (left and right legs).
Change in Ankle Eversion Strength Using Kiio Force Sensor	baseline and month 2	A Kiio Force Sensor will be used to measure the change in ankle strength. Change in strength outcomes at baseline and 2 months will be assessed using Wilcoxon signed rank tests or, if necessary, linear mixed effects models for repeated measures, to account for intra-subject correlation (left and right legs).