Clinical trial NCT03339921
Conditions: Chronic Exertional Compartment Syndrome
Sponsor: 375th Medical Group, Scott Air Force Base
Start date: 2018-12-07; Completion date: 2020-05-01
Enrollment: 3 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
We will investigate the feasibility of a simple outpatient one time injection regimen for the treatment of Chronic Exertional Compartment Syndrome (CECS). We think botulinum toxin injections will be a potentially cost-effective, low-risk alternative to surgery in reducing pain and returning patients to full activity.

Detailed description:
The study will be a prospective cohort pilot study designed to compare Active Duty patients, 18 years of age or older, with Chronic Exertional Compartment Syndrome (CECS) undergoing two different treatment interventions. The first arm will be patients receiving investigational botulinum toxin injections. The second arm will be patients who undergo the standard of care surgical fasciotomy. Both arms will be evaluated for pain relief with the universal pain scale and lower extremity functional index (LEFI) surveys at pre-treatment and again at one, three, and six months post-treatment. Clinical data that will be analyzed for research purposes in both groups include age, sex, height, weight, body mass index, time to diagnosis, minutes of exercise prior to onset of symptoms, minutes of rest before relief of symptoms, LEFI and pain on the Universal Pain Assessment Tool.

Arms: arm 1: Botulinum toxin injections for chronic compartment syndrome arm 2: surgical fasciotomy for chronic compartment syndrome
Interventions: intervention 1: Botulinum toxin injections for chronic compartment syndrome intervention 2: surgical fasciotomy for chronic compartment syndrome
Intervention descriptions: intervention 1: Botulinum toxin will be injected in the upper and lower portion of the affected area with a syringe intervention 2: linear incisions will be made into the affected compartment releasing the underlying fascial layer, reducing the pressure of the compartment

Protocol documents:
Prot_SAP_000.pdf: 
Document Date: 4/27/2020
NCT03339921
Botulinum for Chronic Exertional Compartment Syndrome 


59th Medical Wing Institutional Review Board
Version: 29 September 2016
Revised by PR 2020
1
PROTOCOL FOR NON-EXEMPT RESEARCH INVOLVING HUMAN SUBJECTS
Comparison of Botulinum Toxin to Fasciotomy in Treatment of Chronic Exertional Compartment Syndrome
Title:
IRB #:
FWH20170037H
Principal 
Investigator (PI)
Rank / 
Civ 
Rating
Branc
h
AD/DoD 
Civ/ 
Ctr/Civilian
Dept/Bas
e
Phone #
E-mail
Trevor Brue, DO
Capt
USAF
AD
375MDOS
/
Scott AFB
(512) 508-
4094
trevor.t.brue.mil@mail.mi
l
The research relevance of this protocol focuses on: 
Diagnosis
Treatment
Medical Utilization/Managed Care
Prevention
Medical 
Readiness
Other: 
FOR 59 MDW PERSONNEL ONLY
CONFLICTS OF 
INTEREST:
Do you or any of your research staff have a potential conflict of 
interest to disclose? If unsure, read the below statement before 
proceeding.
 
Yes
 No
If you answer YES above, you must complete the 59 MDW Form 14 – Financial Conflict of Interest Disclosure for 
each individual reporting a conflict and send it via encrypted email to the COI Manager for an official determination 
BEFORE PROCEEDING with this protocol application. The 59th Medical Wing Conflict of Interest Office can assist 
you with any questions you may have regarding conflicts of interest and the COI disclosure process. Contact the COI 
Manager with questions or for additional guidance at: 210-292-5885 or 59mdw.st.hrpp@us.af.mil.
Does the research fall under the purview of any other departments or 
committees?
Yes
No
Radiation Safety Committee 
Institutional Biosafety Committee or Biosafety Officer 
AFMSA Officer of Research and Technology Applications (ORTA) 
59 MDW/SGARB Resource Management Office
1.
LOCATION AND SPONSOR
Collaborating Facilities: N/A
AF Sites Seeking Regional IRB:
Scott AFB Family Medicine Clinic, at 3 St. Elizabeth’s Blvd, Suite 4000, O’Fallon IL 62269/ Trevor Brue, DO (512) 
508-4094
Study Sponsors: N/A
2.
RESEARCH PLAN
Purpose of Study: 
Chronic exertional compartment syndrome (CECS) is a debilitating condition that causes elevation in compartment 
pressure, which can restrict patients from work and exercise. Typical treatment is to relieve compartment pressure 
though surgery. While surgery is effective for 66% of patients, it comes with increased risk and typically takes at least 
8-13 weeks for full return to activity. One unproven alternative for pain relief is the use of botulinum toxin, a paralyzing 
agent. Botulinum toxin injections into the affected area in the lower extremities have been shown in limited trials to be a 
potentially cost effective way to relieve pain and return patients to full activity faster. Therefore, we will investigate the 
feasibility of a simple outpatient one time injection regimen for the treatment of CECS.  We think botulinum toxin 
injections will be a potentially cost-effective, low-risk alternative to surgery in reducing pain and returning patients to full 
activity. 
Hypotheses, Research Questions, or Objectives:


59th Medical Wing Institutional Review Board
Version: 29 September 2016
Revised by PR 2020
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In adult military patients with confirmed CECS by intramuscular pressure (IMP) needle measurements, botulinum toxin 
injections may be a non-inferior effective alternative to surgical fasciotomy in reduction of pain and ability to return to 
full activity.  Therefore, the goals of this project are 1) To determine the long term efficacy of botulinum toxin injections 
in CECS. 2) Compared with current data and previous studies, is botulinum toxin injections non-inferior to current 
treatment regimens for overall pain control and return to full activity.
Significance: 
Currently, the only definitive treatment option for CECS is surgical fasciotomy. A simple outpatient procedure would 
save time, money, and potentially decrease recovery time and improve quality of life. An injection in place of surgery 
would also limit the chances of surgical complications and need for repeat surgical interventions. 
Military Relevance: 
CECS comes at significant cost to the military in terms of medical rehabilitation, surgery, and time lost. Additionally, 
those suffering from CECS are often non-deployable and unable to fully participate in all necessary activities, thus 
requiring waivers to be retained in the military. By finding a cost effective alternative to fasciotomy, with limited side 
effects, we hope to bring treatment costs of CECS down and to also allow soldiers to return to full activity faster and 
without restriction.
Background and Review of Literature: 
The long term objective of this project is to validate botulinum toxin injections as a non-inferior treatment option for pain 
control and ability to return to full activity for adult military members suffering from lower extremity Chronic Exertional 
Compartment Syndrome (CECS), when compared to surgical fasciotomy.1,2 CECS is a debilitating disorder in which 
pressure in muscle compartments increases with exercise and resolves with rest. This causes pain, paresthesia, and 
inability to tolerate exercise.  CECS mainly afflicts the lower extremities, below the knee, but upper extremity CECS has 
also been reported. CECS mainly affects young active adults. At risk groups include males, active duty military 
members, and athletes, both professional and recreational.1,3,4,5
The current standard for definitive management and treatment of CECS is surgical fasciotomy. According to a 2016 
systematic review, surgical intervention for CECS is successful in only 66% of those affected, with 13% of patients 
reporting complications from surgery, and 6% needing a repeat procedure. Definition of success varied across studies, 
but included patient satisfaction, lack of surgical revision, and full return to activity.4 Besides risks and complications, 
surgery also required a mean of 13 weeks to return to full activity when effective.5,6,,7  A 2011 Cohort showed 81% 
overall patient satisfaction with the procedure, but noted best results from fasciotomy were young participants <23 
years old, who underwent isolated anterior compartment release. Satisfaction was defined as being pain free or 
significantly improved on a 5 point pain scale, varying from pain free to worse.8 A smaller 2014 retrospective chart 
review of elite athletes with CECS showed fasciotomy was initially successful in 85% with a mean return to elite activity 
of 10.4 weeks. However, 30.8 % had a return of symptoms within the follow-up period.9
Likewise, conservative treatment options yield mixed results. A systematic review in May of 2016 showed massage, 
gait changes, chemodenervation, and ultrasound-guided (USG) fascial fenestration had few adverse effects, but long 
term results and efficacy were unknown and unverified.10 Another newer therapy, minimal incision fasciotomy was 
effective for returning patients to previous level activity in 94% of patients after 36 months follow up in a prospective 
trial.  Though improved final outcome from regular surgical intervention, average return to activity and return to sport 
was 8 and 13 weeks respectively. 11 
Military personnel comprise a specific patient population for whom outcomes and return to full duty is important for 
continued service and deployment. A 2014 military cohort found women, junior enlisted service members, and the 
Army soldier experienced the highest incidence of CECS. There was also an association between increasing age and 
CECS incidence. The study also found 78% of patients were free from medical discharge or revision after surgery at 
short-term to mid-term follow-up. However, 28% of service members were unable to return to full duty and 45% 
experienced incomplete relief of symptoms. In a similar United Kingdom military study, only 47% of subjects’ symptoms 
improved after surgery.3 Additionally, a 2014 retrospective review of one United States tertiary military facility showed a 
return to full military duty in only 41% of patients who underwent elective fasciotomy for CECS. In that study, 78% of 
patients remained in the military and 71% reported satisfaction with the operative outcome.12
Treatment of CECS with botulinum toxin injections has shown effective and long term relief in initial studies. An initial 
case series; from November 2013; showed that a single series of injections at the proximal and distal end of the 
affected muscle was effective in relieving pain and decreasing intramuscular pressure up to the 9 months of follow up 
in 94% of patients. Sixty-nine percent of those participants did have a decrease in strength, which did not affect overall 
motor function with treatment, but no other adverse effects.1 An additional 2016 case report showed effective pain and 


59th Medical Wing Institutional Review Board
Version: 29 September 2016
Revised by PR 2020
3
paresthesia relief from CECS after 1 set of injections for a recreational female athlete. In this report, the patient’s 
symptoms resolved within 1 week. More importantly, she was able to return to full recreational activity within 4 weeks, 
with no return of symptoms throughout the 14 months of follow up without any weakness or adverse effect.2 However; 
current studies regarding dosage and long term recovery are limited. This study aims to further investigate 
effectiveness of dose dependent botulinum toxin injections to relieve pain and discomfort of CECS, time to return to full 
activity, long term effects of this intervention, and prevention of surgical fasciotomy.  
Bibliography: 
1.
Isner-Horobeti, M.-E., S. P. Dufour, C. Blaes, and J. Lecocq. "Intramuscular Pressure Before and After Botulinum 
Toxin in Chronic Exertional Compartment Syndrome of the Leg: A Preliminary Study." The American Journal of 
Sports Medicine 41.11 (2013): 2558-566. 
2.
Baria, M. R., and J. L. Sellon. "Botulinum Toxin for Chronic Exertional Compartment Syndrome." Clinical Journal of 
Sport Medicine (2016): 1. 
3.
Dunn, J. C., and B. R. Waterman. "Chronic Exertional Compartment Syndrome of the Leg in the Military." Clinics in 
Sports Medicine 33.4 (2014): 693-705. 
4.
Campano, D., J. A. Robaina, N. Kusnezov, J. C. Dunn, and B. R. Waterman. "Surgical Management for Chronic 
Exertional Compartment Syndrome of the Leg: A Systematic Review of the Literature." Arthroscopy: The Journal 
of Arthroscopic & Related Surgery 32.7 (2016): 1478-486. 
5.
Schepsis, A. A., D. Martini, and M. Corbett. "Surgical Management of Exertional Compartment Syndrome of the 
Lower Leg: Long-term Followup." The American Journal of Sports Medicine 21.6 (1993): 811-17. 
6.
Slimmon, D., K. Bennell, P. Brukner, K. Crossley, and S. N. Bell. "Long-Term Outcome of Fasciotomy with Partial 
Fasciectomy for Chronic Exertional Compartment Syndrome of the Lower Leg." American Journal of Sports 
Medicine 30.4 (2002): 581-88. 
7.
Willits, K., N. Pasic, and D. Bryant. "Assessing Long-Term Outcomes in Individuals Undergoing Fasciotomy for 
Chronic Exertional Compartment Syndrome of the Lower Leg (SS-44)." Arthroscopy: The Journal of Arthroscopic 
& Related Surgery 29.6 (2013): n. pag. 
8.
Packer, J. D., M. S. Day, J. T. Nguyen, S. J. Hobart, J. A. Hannafin, and J. D. Metzl. "Functional Outcomes and 
Patient Satisfaction After Fasciotomy for Chronic Exertional Compartment Syndrome." The American Journal of 
Sports Medicine 41.2 (2013): 430-36. 
9.
Rajasekaran, S., and M. M. Hall. "Nonoperative Management of Chronic Exertional Compartment Syndrome." 
Current Sports Medicine Reports 15.3 (2016): 191-98. 
10. Irion, Val, R. A. Magnussen, T. L. Miller, and C. C. Kaeding. "Return to Activity following Fasciotomy for Chronic 
Exertional Compartment Syndrome." Eur J Orthop Surg Traumatol European Journal of Orthopaedic Surgery & 
Traumatology 24.7 (2014): 1223-228.
11. Maffulli, N., M. Loppini, F. Spiezia, A. D’Addona, and G. D. Maffulli. "Single Minimal Incision Fasciotomy for 
Chronic Exertional Compartment Syndrome of the Lower Leg." Journal of Orthopaedic Surgery and Research J 
Orthop Surg Res 11.1 (2016): n. pag. 
12. Mccallum, J. R., J. B. Cook, A. C. Hines, J. S. Shaha, J. W. Jex, and J. R. Orchowski. "Return to Duty After 
Elective Fasciotomy for Chronic Exertional Compartment Syndrome." Foot & Ankle International 35.9 (2014): 871-
75. 
13. Pedowitz, R. A., A. R. Hargens, S. J. Mubarak, and D. H. Gershuni. "Modified Criteria for the Objective 
Diagnosis of Chronic Compartment Syndrome of the Leg." The American Journal of Sports Medicine 
18.1 (1990): 35-40. 
14. Aweid, O., A. Del Buono, P. Malliaras, H. Iqbal, D. Morrissey, N. Maffulli, and N. Padhiar. "Systematic 
Review and Recommendations for Intracompartmental Pressure Monitoring in Diagnosing Chronic 
Exertional Compartment Syndrome of the Leg." Clinical Journal of Sport Medicine 22.4 (2012): 356-70. 
3.
RESEARCH DESIGN AND METHODS
Research Design and Methods: 
The study will be a prospective cohort pilot study designed to compare Active Duty patients, 18 years of age or older, 
with CECS undergoing two different treatment interventions. The first arm will be patients receiving investigational 
botulinum toxin injections. The second arm will be patients who undergo the standard of care surgical fasciotomy. 
Both arms will be evaluated for pain relief with the universal pain scale and lower extremity functional index (LEFI) 
surveys at pre-treatment and again at one, three, and six months post-treatment. At the six month follow up, subjects 
will be asked the Satisfaction Survey (in-person, via Survey Monkey or Google Forms). Clinical data that will be 
analyzed for research purposes in both groups include age, sex, height, weight, body mass index, time to diagnosis, 
minutes of exercise prior to onset of symptoms, minutes of rest before relief of symptoms, LEFI and pain on the 
Universal Pain Assessment Tool.


59th Medical Wing Institutional Review Board
Version: 29 September 2016
Revised by PR 2020
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In addition, we will be conducting a retrospective review from July 1, 2016 through June 30, 2017 of patients who 
have been diagnosed with CECS and have undergone surgical fasciotomy.  They will be asked to recall their 
symptoms both before and six months after their surgery, in order to complete the LEFI and Universal Pain 
Assessment Tool (in-person, via Survey Monkey or Google Forms). They will also be asked if they were satisfied 
with their treatment.  A HIPAA Waiver Request will be used to access medical records and contact these individuals, 
followed by each subject being verbally consented to participate in the study prior to completing the LEFI and 
universal pain scale surveys (in-person, via Survey Monkey or Google Forms).  If the subjects refuse to be 
consented, then no data will be gathered from the subjects or their medical records.
a.
Interventions and Observations: 
If CECS is diagnosed by intramuscular pressure (IMP) elevation, patients will be offered Botulinum toxin injection 
regimen into the affected compartment or referral to orthopedic surgeon for a possible surgical fasciotomy. Patients 
will be provided information regarding both Botulinum toxin injections and fasciotomy. Patients will be allowed to 
discuss fasciotomy with a surgeon prior to making a decision to participate in the study, if desired.  Potential side 
effects of Botulinum toxin injection include possible bleeding, pain, infection, general muscle weakness, muscular 
atrophy, flu-like symptoms, breathing and swallowing difficulties and death. Potential side effects of fasciotomy 
include surgical site pain, bleeding, recurrence of symptoms, scarring, muscle weakness, nerve damage, hematoma, 
need for repeat operation, infection, reactions to anesthesia (e.g. anaphylaxis), blood clot, muscle wasting (atrophy), and 
death. These will be explained to participants during the consent discussion.
For those diagnosed with CECS and desire Botulinum toxin injections, they will receive 2 injections per affected 
compartment. Up to 50 units of Botulinum toxin will be injected into the proximal and distal portions of the 
compartment for a maximum total dose of 100 units.1,2 A solution of 100 units of Botulinum toxin per 2 mL of normal 
saline will be used for all injections. Standard sterile technique will be followed. Insertion in to the correct 
compartment will be accomplished using general landmarks. The compartment will be separated into thirds 
measuring from the tibial plateau to the head of the calcaneus. Injections will be given at approximately 1/3 the 
distance from the tibial plateau for the proximal injection and 2/3 the distance from the tibial plateau for the distal 
injection. If the lateral or deep posterior compartment is affected, a total of 50 units Botulinum toxin will be given, 25 
units per injection. If the anterior or superficial posterior compartment is affected, a total of 100 units Botulinum toxin 
will be given, 50 units per injection.  Of note, CECS mainly affects the anterior and lateral compartments and is rarely 
seen in the superficial posterior or deep posterior areas.
For those diagnosed with CECS and desire surgical fasciotomy, the team will discuss the fasciotomy procedure and 
risks as mentioned above. For the procedure, the patient will be placed under general anesthesia and then linear 
incisions will be made into the affected compartment releasing the underlying fascial layer, reducing the pressure of 
the compartment. The entire procedure will be accomplished in a sterile fashion.  Further details and scheduling will 
be per the orthopedic surgeon’s recommendations. 
After the initial Botulinum toxin injection regimen or fasciotomy, patients will be assessed at 1 month, 3 months, and 
6 months with the LEFI and universal pain scale. Primary outcome will be pain reduction. Adequate pain reduction 
will be rated as less than 3 on the universal pain scale. Secondary outcomes will include return to full activity and 
patient satisfaction. Full activity is defined as able to run 1.5 miles and complete work duties with either no pain or 
pain that can be ignored.  To assess patient satisfaction, patients will be asked if they were or were not satisfied with 
the Botulinum toxin injections at the 6 month visit.
b.
Setting: 
The study will be carried out in the 375 MDOS outpatient O’Fallon Family Medicine Residency Clinic located at 3 St. 
Elizabeth’s Blvd, Suite 4000, O’Fallon, ILThe clinic is also part of a family medicine residency program. All 
counseling, injections, and follow-up will be done in the family medicine clinic. All standard of care tests for pre-
screening of subjects will be performed at the Scott Air Force Base medical group radiology and laboratory facilities.  
These tests include blood tests, X-rays, physical exam and intramuscular compartment pressure readings.
c.
Date(s): 
For the prospective portion of the study for patients receiving Botulinum toxin injections, expected timeframe for data 
collection is April 2017 through April 2020.
For the retrospective portion of the study, we will review medical results and pain assessments from patients who 
had a surgical fasciotomy during the time period of July 1, 2016 through June 30, 2017.
d.
Subjects:


59th Medical Wing Institutional Review Board
Version: 29 September 2016
Revised by PR 2020
5
Patients will be active duty military adults, 18 years of age or older, who have clinical signs and symptoms of chronic 
exertional compartment syndrome in any muscular compartment of the lower leg.  All patients referred to the sports 
medicine clinic for leg pain will be screened for possible inclusion into the study, following standard of care clinical 
tests. After an initial standard of care evaluation, if CECS is suspected, each subject will be asked to participate in 
the study and will be formally consented by a member of the research team.
Other exertional causes of leg pain will be ruled out by a standard of care clinical examination (general, orthopedic, 
neurologic, and functional) and supporting workup. This will include plain radiographs of the knee, tibia, fibula, and 
ankle on the affected side of the lower extremity. Any patient with an abnormal finding not consistent with CECS, 
such as a stress fracture, will be ruled out from participating in the research study. Patients will have tried 
conservative treatment for at least 2 months prior to compartment testing to include rest, stretching, ice, and 
NSAIDs. All patients reporting lower extremity pain will be examined by a physician on the study team to confirm 
CECS under the direct supervision of Dr. Brue. 
Intramuscular pressure in lower leg compartments will be obtained by IMP needle insertion (standard of care) into all 
four compartments of both lower legs before and after exercise. Infection risk will be decreased by sterilizing the 
puncture site with chlorhexidine swabs. Pain will be decreased by injecting 0.5 mL of 1% lidocaine with epinephrine 
superficially to anesthetize the skin. Pressure will be transmitted to a pressure transducer for measurement in mm 
Hg. The exercise portion will be standardized by having patients run on the same treadmill with enough speed until 
their symptoms begin.  After symptoms begin, the patient will be asked to continue running until he or she cannot 
tolerate, at which time the exercise will be stopped and the patient will lie supine for repeat intramuscular pressure 
measurements. Definitive diagnosis of CECS will be based on intramuscular pressure elevations according to 
Pedowitz et al. This includes 1) a pre-exercise pressure greater than or equal to 15 mm Hg and 2) a 1-5 minute post-
exercise pressure of greater than or equal to 30 mm HG.13, 14
e.
Inclusion/Exclusion Criteria: 
Inclusion Criteria
• Adult ages 18-65
• Active duty military
• Unable to run 1.5 miles without producing symptoms, including aching, burning, numbness, 
tingling, or weakness in the affected limb
• Failed conservative treatment over a period of 2 months, including trial of rest, 
NSAIDs, icing, and stretching routine
• Meets standard of care clinical diagnostic intramuscular compartment pressure criteria for 
CECS, based on standardized IMP needle testing. See below for testing protocol and 
criteria.
Exclusion Criteria
• Prior Botulinum toxin injections into the affected limb
• Prior compartment release of the affected limb
• Pregnant or becomes pregnant during the study
• Standard of care clinical exams indicating other more likely causes of leg pain
f.
Source of Research Material: 
Will you be using private information in this 
study?
 No – Only using publically available information
Yes – 
 protected health information (PHI) held by a covered entity
 other types of private information 
Describe: 
If Yes, 
 research information (non-PHI) 
that is not publically available (i.e., 
student records)
Describe: 
Use of identifiers with private 
information
Identifiers to be Used?
Column A
Looked at 
by research 
team
Column B
Recorded 
on 
enrollment 
log, subject 
list, or key 
list
Column C
Recorded on 
data collection 
tool (survey, 
spreadsheet, 
etc.)
Column D
Recorded 
on 
specimen 
containers
Column E
Shared w/ 
others not 
on research 
team
Column F
Stored 
after 
study 
ended


59th Medical Wing Institutional Review Board
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Revised by PR 2020
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NONE
Names
Study codes linked to 
individuals’ identities 
using a key only 
accessible by the 
researcher
Addresses
Dates (except year)
Ages over 89
Phone/Fax Numbers
E-mails
- SSNs
- Scrambled SSNs
- last four of SSN
Specify:
Last 4 SSN
Specify:
Last 4 SSN
Specify:
Last 4 SSN
Specify:
Specify:
Specify:
Numbers:
- Medical record #
- Account #
- Certificate/license #
- Health plan beneficiary 
#
- Vehicle identifier/serial 
#
- License plate #
- Device identifier/serial #
Specify:
Medical 
record #
Specify:
Medical 
record #
Specify:
Medical 
Record #
Specify:
Specify:
Specify:
Web URLs or IP 
addresses
- Biometric Identifiers, 
including finger/voice 
prints
- Full-face photo images 
and comparable images
Specify:
Specify:
Specify:
Specify:
Specify:
Specify:
Any other pre-existing 
unique identifying 
number, characteristic, or 
code
Coding Plan?
Not applicable, no identifiable information will be collected
Describe the method that will 
be used to create and assign 
unique study codes to data.
Patients will be identified using their initials and last four of their SSN. 
Describe the method that will 
be used to create and assign 
unique study codes to 
specimens.
 N/A, not collecting specimens
Describe: 
What is the format of the key?
 Paper
  Electronic
Who will have access to the 
key?
Only principal investigators
Where will the key be stored 
and how will it be protected?
Location(s): The key will be stored in principal investigator’s locked office in a locked 
drawer.
Confidentiality measures: All electronic information will be stored on a secure 
network with a double password protected document
Complete the table. 


59th Medical Wing Institutional Review Board
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Source of Research Material per Participant 
(Procedures)
# Routine 
Care
# Research 
Driven
# Total 
Procedures
X-rays, blood samples
1
0
1
Intramuscular compartment pressure readings
1
0
1
Lower extremity functional index
1
3
4
Universal Pain Scale
1
3
4
Satisfaction survey
0
1
1
Urine Pregnancy Test
0
1
1
g. Instrumentation:
The Stryker Intra-compartmental pressure monitor will be used for the standard of care diagnosis of compartment 
syndrome. 
4.
HUMAN SUBJECT PROTECTION
Recruitment and Consent Processes: 
All patients referred to the sports medicine clinic for leg pain will be screened for possible inclusion into the study, 
following standard of care clinical tests. After an initial standard of care evaluation, if CECS is suspected, each 
subject will be tested for compartment syndrome using standard of care clinical tests. If they are diagnosed with 
CECS, they will be asked to participate in the study and will be formally consented by a member of the research 
team.
Other exertional causes of leg pain will be ruled out by a standard of care clinical examination (general, orthopedic, 
neurologic, and functional) and supporting workup. These tests will include plain radiographs of the knee, tibia, 
fibula, and ankle on the affected side of the lower extremity.  Any patient with an abnormal finding not consistent with 
CECS, such as stress fracture, will be ruled out from participating in the research study. Patients will have tried 
conservative treatment for at least 2 months prior to compartment testing to include rest, stretching, ice, and 
NSAIDs. All patients reporting lower extremity pain will be examined by one of the study physicians to confirm 
CECS, under direct supervision of Dr. Brue.
Consent Processes:
 Telephone
Submit Form F – HIPAA and Consent 
Waiver and Alteration Form.
X
Will obtain consent 
without a signature
Is the information collected 
for the study health 
information?
 Yes, submit Form F – HIPAA and 
Consent Waiver and Alteration Form.
How will 
you 
consent 
subjects 
to 
participat
e in the 
research?
X
Will exclude some of the required elements of 
consent in the consent form, information sheet, or 
consent process
Submit Form F – HIPAA and Consent 
Waiver and Alteration Form.
Prospective Subjects: Informed Consent and HIPAA Authorization will be sought in advance from each prospective 
subject and appropriately documented in accordance with 32 CFR 219.117. Potential subjects will be notified about 
the study either through posted advertisements or by their primary care provider. Investigators will provide a written 
copy of the Informed Consent (ICD) and HIPAA Authorization (HIPAA) to the subject. The subject may decline to 
participate without prejudice. At the subject’s discretion, they may take the ICD and HIPAA home to discuss further 
prior to making a decision. If the subject consents, a copy of the ICD and HIPAA will be given to them. No vulnerable 
populations are included in this research study. Subjects who cannot provide ICD and HIPAA will not be allowed to 
patriciate. No Legally Authorized Representatives will be utilized. Some patients may be patients of the PI or AI, 
however, they will have the study staff recruit their patients to prevent any misconception of coercion or undue 
influence.
Retrospective Subjects: Each subject will be verbally consented over the phone using the Telephone Consent prior 
to being asked any questions. The subject may decline to participate without prejudice. An approved HIPAA waiver 
is being utilized.
Recruiting Service 
Members
Will you be recruiting service members in a group setting? 
 
Yes
  
No
Participation Compensation: 


59th Medical Wing Institutional Review Board
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Subjects will not be paid for participation in this study.
Assent Process: N/A
Benefits: 
Potential benefits will be a relief of symptoms, avoidance of surgery, and return to full activity in the military setting.
Risks: 
Procedural risks for an IMP needle insertion for intramuscular pressure testing may include pain, bleeding, and 
infection. There is a potential for no relief of CECS symptoms with either treatment intervention. Potential side effects 
of Botulinum toxin injections include possible pain, bleeding, infection, general muscle weakness, muscular atrophy, 
flu-like symptoms, breathing and swallowing difficulties and death. Potential side effects of fasciotomy include 
surgical site pain, bleeding, recurrence of symptoms, scarring, muscle weakness, nerve damage, hematoma, need for 
repeat operation, infection, reactions to anesthesia (e.g. anaphylaxis), blood clot, muscle wasting (atrophy), and death.
Costs: N/A
Safeguards for Protecting Information: 
The research consents will be stored in a locked cabinet in a locked room.  Medical records will be annotated with 
ICD-10 code Z00.6 to reflect the subject’s participation in a research study. All research data including patient 
demographics will be kept in an electronic database, which will be encrypted, double password protected and the 
access will be restricted.  The research data will be coded and any links to identifiable data will be destroyed as soon 
as the Final Report Approval has been obtained from the IRB.
Data and Specimen Storage Plan
How will coded or identifiable data/specimens be 
stored?
X
Paper data, including completed consent forms
The research data will be coded to mask the identity of the 
individual. They will be kept in a locked cabinet in a locked 
office.
X
Electronic data
X
SSNs, Scrambled SSNs, or last four of SSNs
All research data will be kept in an electronic database, 
which will be encrypted, double password protected and 
the access will be restricted.
X
Long-term storage (following completion of the 
study and inactivation of IRB approval)
Once a Final Report has been approved by the IRB, all 
patient identifiers will be removed. The anonymized 
research data will not be utilized for further research 
activity beyond the protocol stipulations without additional 
IRB approval. The de-identified subject data, signed ICD 
and HIPAA documents, and the Regulatory Binder will be 
housed 3 years after the final report has been approved by 
the IRB.
Safeguards for Protecting Subjects Relative to Reasonably Expected Risks: 
The subjects are not expected to experience any physical discomfort, psychological distress, or long term significant 
behavioral effects from their PHI being included in this study.  The risk of invasion of private information is minimal as 
few identifiers will be used and will be protected, and any PHI will only be viewed by the investigators.  Additionally, 
the data would not embarrass or disadvantage the participants if confidentiality were violated.
Categories of subjects: None
Clinical Care: 
All subjects will receive standard care for any illness or disease found during the course of this study. At no time will 
this study preclude them from receiving any treatment for diseases related or unrelated to the study. 
Injury Compensation: N/A


59th Medical Wing Institutional Review Board
Version: 29 September 2016
Revised by PR 2020
9
Data Safety 
Monitoring
 N/A – none of the situations listed above apply
5.
ALTERNATIVES
Alternatives: 
Alternatives to participation in the study are continued conservative management to include rest, stretching, icing, and 
anti-inflammatory medications. Other options are to proceed with standard of care surgical fasciotomy or to do nothing. 
6.
DATA ANALYSIS
Data Analysis: 
Head-to-head comparison of patients undergoing or who have undergone standard of care surgical fasciotomy and 
investigational Botulinum toxin injections will be analyzed. Measures addressed will be pain severity, return to full 
activity, Lower Extremity Function index, and patient satisfaction over the course of pre-treatment, post-treatment, 
and 1, 3, 6 month follow-up visits. 
A power analysis, shown below, was completed for this pilot study. Assuming equal sample sizes of groups, 2-tail 
alpha of .05, power=.8, and 67% of fasciotomy group will have no pain (i.e. pain < 3).4
1. 75% of injection group, no pain - n=1008 total
2. 80% of injection group, no pain - n=360 total
3. 85% of injection group, no pain - n=176 total
4. 90% of injection group, no pain - n=98 total
5. 95% of injection group, no pain - n=60 total
As CECS is an infrequent diagnosis, this pilot study will have difficulty over the course of the year to obtain enough 
sample size for statistical significance. However, the hope is to obtain a promising trend and eventually expand the 
study to obtain significance pending initial results.
Outcome Measures: 
For the prospective portion of the study, the primary outcome will be pain reduction from either a standard of care 
surgical fasciotomy or an investigational Botulinum toxin treatment regimen. Adequate pain reduction will be rated as 
less than 3 on the universal pain scale. Secondary outcomes will include return to full activity and patient satisfaction. 
Full activity is defined as being able to run 1.5 miles and complete work duties with either no pain or pain that can be 
ignored.  To assess patient satisfaction, patients will be asked if they were or were not satisfied with their surgical 
fasciotomy or their Botulinum toxin injections during their 6 month follow-up visit.
For the retrospective portion of the study, the same measures will be addressed for subjects who have undergone a 
standard of care surgical fasciotomy, but only on a pre- and post-treatment basis.
Sample Size Estimation/Power Analysis:
The expected sample size for the prospective portion of the study is 15. The expected sample size for the 
retrospective review is 10. 
Statistical Analysis: 
The primary measure to be analyzed will be comparing pre- and post-treatment pain for each of the two treatment 
regimens using the universal pain scale. Additionally, participants will be evaluated for return to duty, overall patient 
satisfaction, and the Lower Extremity Functional Index will be compared pre- and post-treatment. The study team will 
complete the statistical analysis. 
Number of Subjects: 
# Planned to Enroll
# Enrolled
# Planned to Complete 
Study
TOTAL


59th Medical Wing Institutional Review Board
Version: 29 September 2016
Revised by PR 2020
10
Number of Subjects at Scott 
AFB
15
0
15
15
Number of Data Records Entered into the Study: 
# Planned to Enroll
# Enrolled
# Planned to Complete 
Study
TOTAL
Number of Subjects at Scott 
AFB
10
0
10
10
7.
STUDY DURATION
Duration of Study: 
Approximate duration of the study: 2 years
8.
LOCAL AND EXTERNAL SUPPORT SERVICES
Describe the plan for training personnel who are not 
part of the research team and will be administering 
intervention(s).
 Not applicable – no training of non-study personnel 
required
9.
INTRAMURAL (GME) AND EXTRAMURAL FUNDING SUPPORT
Intramural (GME) and Extramural Funding Support: None
10. DRUGS, BIOLOGICS, DIETARY SUPPLEMENTS, AND MEDICAL DEVICES
Does the study plan dictate the use of any of the following?
A drug
 
Yes 
 No
A biologic
 
Yes 
 No
A compound intended to affect structure or any function of the body
 
Yes 
 No
A dietary supplement or substance generally recognized as safe that will be used to diagnose, 
cure, mitigate, treat, or prevent disease
 
Yes
 No
A medical device
 
Yes 
 No
10A. List all drugs covered by an Investigational New Drug (IND) from the FDA (approved or submitted) 
Name of Drug
Dose(s) directed by 
protocol
Route(s) of 
administration
IND Number or 
Date Submitted
IND Holder 
(Sponsor)
Botulinum Toxin
50-100u
IM
134278/Exempted 
10B. List all FDA approved drugs being used in accordance with FDA approved labeling
Name of Drug
Dose(s) directed by protocol
Route(s) of administration
 N/A, no FDA approved drugs being used according to the labeling
10C. List all FDA approved drugs used for an unapproved use (“off-label”) 
Name of Drug
Dose(s) directed by protocol
Route(s) of administration
Botulinum Toxin
50u per injection
IM to treat CECS
10D. List all biologics, compounds and dietary supplements 
 N/A, no biologics, compounds and dietary supplements
10E. List all devices covered by an Investigational Device Exemption (IDE) from the FDA (approved or submitted)
 N/A, an IDE has not been submitted to or approved by the FDA
10F. List all FDA approved devices used for an unapproved use (“off-label”) 
 N/A, no FDA approved devices being used “off-label”
10G. List all unapproved devices. 


59th Medical Wing Institutional Review Board
Version: 29 September 2016
Revised by PR 2020
11
 N/A, no unapproved devices
10H. Device Storage 
Location(s):
Is this research an “applicable clinical trial” which must be registered on ClinicalTrials.gov?
x Yes, Local Investigator registered the trial NCT03339921
Use of a placebo in place of standard therapy:
Is a placebo being used in place of standard 
therapy?
 No
 Yes
11. MEDICAL RESEARCH AREA
Analytical Chemistry
Anatomy
Anesthesiology
Biochemistry
Cardiovascular Surgery
Cardiology
Cell Biology
Dentistry
Dermatology
Dietetics
Electrophysiology
Endocrinology
Emergency medicine
Gastroenterology
General Surgery
Hematology
Histology
Immunology/Allergy
Infectious Disease
Microbiology
Molecular Biology
Neonatology
Neurology
Neurosurgery
Nursing
OB/GYN
Occupational Medicine
Occupational Therapy
Oncology
Ophthalmology
Oral/Maxillofacial 
Surgery
Orthopedics
Pathology
Pediatrics
Pharmacology
Physical Therapy
Mental Health
Radiology/Imaging
Urology
Wellness
Other:
Sports Medicine, Musculoskeletal
12. ATTACHMENTS
1.
Form A, Signature Sheet
2.
Form A-2, Study Personnel Listing
3.
Form D, Informed Consent Document
4.
HIPAA and Consent Waiver and Alteration Form
5.
Form O, Use of a an Investigational Drug in Research
6.
Universal Pain Scale
7.
Lower Extremity Functional Index (LEFI)
8.
Form E, HIPAA Authorization Document
9.
FDA Acknowledge/Exempt IND Determination Letter
10. Telephone Consent
11. Satisfaction Survey
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