Ankle InjuriesPhase 2NCT02892500
Investigation of Corticosteroid Versus Placebo Injection in Patients With Syndesmotic Ligament Injury or High Ankle Sprain
A Phase 2 study testing bupivacaine hydrochloride and betamethasone sodium phosphate and bupivacaine hydrochloride in people with Ankle Injuries, run by Sanford Health at 1 site in United States.
Trial summary
This study evaluates the use of corticosteroids acutely as an adjuvant treatment of the high ankle sprain. Subjects will receive either a corticosteroid or a local anesthetic injection. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Ankle Injuries
- What is being tested?
- bupivacaine hydrochloride and betamethasone sodium phosphate and bupivacaine hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to 21 Sep 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16 years or older
- Musculoskeletal ultrasound performed which demonstrates injury pattern consistent with high ankle sprain.
- Must sign the informed consent form and agree to meet the needs of the study
- Clinically and ultra sound confirmed and isolated syndesmotic ligament injury or high ankle sprain without associated fracture
- Injury occurred within the previous 7 days
Who cannot join
- Surgical intervention required to stabilize the ankle
- Unable to read and understand the consent form
- Unable to meet the needs of the follow-up examinations
- Allergic to the betamethasone
- Current fungal infection
- Pregnancy or currently breast feeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Sanford Orthopedics and Sports Medicine
Fargo, North Dakota, 58103
About this study
Official title: Single-site, Double Blinded, Randomized Investigation of Corticosteroid Versus Placebo Injection Under Ultrasound Guidance in Patients With Syndesmotic Ligament Injury or High Ankle Sprain
This study evaluates the use of corticosteroids acutely as an adjuvant treatment of the high ankle sprain. Subjects will receive either a corticosteroid or a local anesthetic injection.
Read the detailed description
The term "high ankle sprain" refers to injury to the syndesmotic ligaments of the ankle. It has become a much more common injury comprising up to 24.6% of all ankle sprains , with an incidence of 2.4 per 1000 athlete exposures. These can present a significant therapeutic challenge for the sports physician and typically result in a prolonged morbidity and delayed return to activity. The literature shows a lack of information for definitive care of these athletes. Typical recovery for the high ankle sprain is almost twice as long as the more common lateral ankle inversion sprain with a mean time to return to play of 45 days. There is also a higher incidence of residual chronic pain comparing high ankle sprains to an isolated lateral ankle sprain. The current standard for treatment of this injury has been to depend on symptomatic treatment with an initial phase of rest and protected splinting. This is followed by the use of NSAID's with a graduated rehabilitation program to reduce swelling, improve range of motion, and regain strength and proprioception of the ankle. This is followed by protective taping or bracing and return to activities as tolerated. Inflammation is one of the body's first reactions to injury. Release of damaged cells and tissue debris occurs upon injury. These expelled particles act as antigens to stimulate a nonspecific immune response and to cause the proliferation of leukocytes. Local blood flow increases to transport the polymorphonuclear leukocytes, macrophages, and plasma proteins to the injured area. A redistribution of arteriolar flow produces stasis and hypoxia at the injury site. The resulting infiltration of tissues by the leukocytes, plasma proteins, and fluid causes the redness, swelling, and pain that are characteristic of inflammation. Initially, the inflammatory reaction serves several important purposes. The influx of leukocytes facilitates the process of phagocytosis and the removal of damaged cells and other particulate matter. Pain and tenderness remind the patient to protect the injured area; however, the inflammatory reaction eventually becomes counterproductive. The mechanism of corticosteroid action includes a reduction of the inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. They also inhibit the release of destructive enzymes that attack the injury debris and destroy normal tissue indiscriminately. Additionally, new research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins, which contribute to the inflammatory process. There are no previous prospective, randomized studies that look at utilization of corticosteroids in treatment of the high ankle sprain. Only anecdotal information is available in simple case reports for treatment. There was one study looking at treatment with platelet rich plasma injection which demonstrated shorter return to play times and less long term residual pain.
- Conditions
- Ankle Injuries
- Being tested
- bupivacaine hydrochloride and betamethasone sodium phosphate, bupivacaine hydrochloride
- Medical subject headings
- Ankle Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bupivacaine hydrochloride and betamethasone sodium phosphateDrug
Also called Marcaine, Celestone, Soluspan,
5ml of 0.25% bupivacaine hydrochloride and 2 ml of 3mg/ml betamethasone sodium phosphate one injection into the inferior tibiofibular ligament
bupivacaine hydrochlorideDrug
Also called Marcaine
5ml of bupivacaine hydrochloride into the tibiofibular ligament
| Study group | Role | What they receive |
|---|---|---|
| bupivacaine hydrochloride and betamethasone sodium phosphate | Experimental | When the patient has been randomized to either group, a licensed provider under the direction of the PI, will utilize the ultrasound to identify the inferior tibiofibular ligament (syndesmotic ligament). This provider that performs the injection will not be involved in any follow-up visits or return to play review. When appropriate positioning is confirmed the area will be injected with a mixture of 5 ml of 0.25 % bupivacaine hydrochloride and 2 ml of 3 mg/ml betamethasone sodium phosphate (Celestone® Soluspan®) (BTM) Receives: Drug: bupivacaine hydrochloride and betamethasone sodium phosphate |
| bupivacaine hydrochloride | Active comparator | When the patient has been randomized to either group, a licensed provider under the direction of the PI, will utilize the ultrasound to identify the inferior tibiofibular ligament (syndesmotic ligament). This provider that performs the injection will not be involved in any follow-up visits or return to play review. When appropriate positioning is confirmed, the area will be injected with 5ml of bupivacaine hydrochloride. Receives: Drug: bupivacaine hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare Between the Two Groups the Time to Return to Previous Levels of Activity
Measured: One year
Secondary outcomes (1)
Compare Patient Reported Outcomes Between the Two Groups Using the Foot and Ankle Ability Measure (FAAM) Tool.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2016 (estimated)
- Study startApr 2016
- Primary completion21 Sep 2016
- Study completion21 Sep 2016
Why it stopped: Inability to enroll subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Ankle InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanford Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bruce Piatt, MD, Principal investigator, Orthopedic Surgeon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02892500
- Sponsor's protocol ID
- SanfordHealth
- Status last verified
- Jan 2024
- First submitted
- 23 Aug 2016
- Last updated
- 13 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Hunt KJ, George E, Harris AH, Dragoo JL. Epidemiology of syndesmosis injuries in intercollegiate football: incidence and risk factors from National Collegiate Athletic Association injury surveillance system data from 2004-2005 to 2008-2009. Clin J Sport Med. 2013 Jul;23(4):278-82. doi: 10.1097/JSM.0b013e31827ee829.
PubMed 23339895Hopkinson WJ, St Pierre P, Ryan JB, Wheeler JH. Syndesmosis sprains of the ankle. Foot Ankle. 1990 Jun;10(6):325-30. doi: 10.1177/107110079001000607.
PubMed 2113510Wright RW, Barile RJ, Surprenant DA, Matava MJ. Ankle syndesmosis sprains in national hockey league players. Am J Sports Med. 2004 Dec;32(8):1941-5. doi: 10.1177/0363546504264581.
PubMed 15572325Katznelson A, Lin E, Militiano J. Ruptures of the ligaments about the tibio-fibular syndesmosis. Injury. 1983 Nov;15(3):170-2. doi: 10.1016/0020-1383(83)90007-4.
PubMed 6642626Nussbaum ED, Hosea TM, Sieler SD, Incremona BR, Kessler DE. Prospective evaluation of syndesmotic ankle sprains without diastasis. Am J Sports Med. 2001 Jan-Feb;29(1):31-5. doi: 10.1177/03635465010290011001.
PubMed 11206253Cole BJ, Schumacher HR Jr. Injectable corticosteroids in modern practice. J Am Acad Orthop Surg. 2005 Jan-Feb;13(1):37-46. doi: 10.5435/00124635-200501000-00006.
PubMed 15712981Mei-Dan O, Kots E, Barchilon V, Massarwe S, Nyska M, Mann G. A dynamic ultrasound examination for the diagnosis of ankle syndesmotic injury in professional athletes: a preliminary study. Am J Sports Med. 2009 May;37(5):1009-16. doi: 10.1177/0363546508331202. Epub 2009 Mar 31.
PubMed 19336613Laver L, Carmont MR, McConkey MO, Palmanovich E, Yaacobi E, Mann G, Nyska M, Kots E, Mei-Dan O. Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in elite athletes: a randomized control trial. Knee Surg Sports Traumatol Arthrosc. 2015 Nov;23(11):3383-92. doi: 10.1007/s00167-014-3119-x. Epub 2014 Jun 18.
PubMed 24938396
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-site, Double Blinded, Randomized Investigation of Corticosteroid Versus Placebo Injection Under Ultrasound Guidance in Patients With Syndesmotic Ligament Injury or High Ankle Sprain
- ClinicalTrials.gov ID
- NCT02892500
- Acronym / sponsor ID
- SanfordHealth
- Conditions
- Ankle Injuries
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inability to enroll subjects
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Sanford HealthUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- 21 Sep 2016 (actual)
- Study completion
- 21 Sep 2016 (actual)
- First posted
- 8 Sep 2016 (estimated)
- Results
- Posted 2 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the use of corticosteroids acutely as an adjuvant treatment of the high ankle sprain. Subjects will receive either a corticosteroid or a local anesthetic injection.
Detailed description
The term "high ankle sprain" refers to injury to the syndesmotic ligaments of the ankle. It has become a much more common injury comprising up to 24.6% of all ankle sprains , with an incidence of 2.4 per 1000 athlete exposures. These can present a significant therapeutic challenge for the sports physician and typically result in a prolonged morbidity and delayed return to activity. The literature shows a lack of information for definitive care of these athletes. Typical recovery for the high ankle sprain is almost twice as long as the more common lateral ankle inversion sprain with a mean time to return to play of 45 days. There is also a higher incidence of residual chronic pain comparing high ankle sprains to an isolated lateral ankle sprain. The current standard for treatment of this injury has been to depend on symptomatic treatment with an initial phase of rest and protected splinting. This is followed by the use of NSAID's with a graduated rehabilitation program to reduce swelling, improve range of motion, and regain strength and proprioception of the ankle. This is followed by protective taping or bracing and return to activities as tolerated. Inflammation is one of the body's first reactions to injury. Release of damaged cells and tissue debris occurs upon injury. These expelled particles act as antigens to stimulate a nonspecific immune response and to cause the proliferation of leukocytes. Local blood flow increases to transport the polymorphonuclear leukocytes, macrophages, and plasma proteins to the injured area. A redistribution of arteriolar flow produces stasis and hypoxia at the injury site. The resulting infiltration of tissues by the leukocytes, plasma proteins, and fluid causes the redness, swelling, and pain that are characteristic of inflammation. Initially, the inflammatory reaction serves several important purposes. The influx of leukocytes facilitates the process of phagocytosis and the removal of damaged cells and other particulate matter. Pain and tenderness remind the patient to protect the injured area; however, the inflammatory reaction eventually becomes counterproductive. The mechanism of corticosteroid action includes a reduction of the inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. They also inhibit the release of destructive enzymes that attack the injury debris and destroy normal tissue indiscriminately. Additionally, new research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins, which contribute to the inflammatory process. There are no previous prospective, randomized studies that look at utilization of corticosteroids in treatment of the high ankle sprain. Only anecdotal information is available in simple case reports for treatment. There was one study looking at treatment with platelet rich plasma injection which demonstrated shorter return to play times and less long term residual pain.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| bupivacaine hydrochloride and betamethasone sodium phosphate | Experimental | Drug: bupivacaine hydrochloride and betamethasone sodium phosphateWhen the patient has been randomized to either group, a licensed provider under the direction of the PI, will utilize the ultrasound to identify the inferior tibiofibular ligament (syndesmotic ligament). This provider that performs the injection will not be involved in any follow-up visits or return to play review. When appropriate positioning is confirmed the area will be injected with a mixture of 5 ml of 0.25 % bupivacaine hydrochloride and 2 ml of 3 mg/ml betamethasone sodium phosphate (Celestone® Soluspan®) (BTM) |
| bupivacaine hydrochloride | Active comparator | Drug: bupivacaine hydrochlorideWhen the patient has been randomized to either group, a licensed provider under the direction of the PI, will utilize the ultrasound to identify the inferior tibiofibular ligament (syndesmotic ligament). This provider that performs the injection will not be involved in any follow-up visits or return to play review. When appropriate positioning is confirmed, the area will be injected with 5ml of bupivacaine hydrochloride. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Age 16 years or older
- Musculoskeletal ultrasound performed which demonstrates injury pattern consistent with high ankle sprain.
- Must sign the informed consent form and agree to meet the needs of the study
- Clinically and ultra sound confirmed and isolated syndesmotic ligament injury or high ankle sprain without associated fracture
- Injury occurred within the previous 7 days
Key exclusion criteria (6 listed)
- Surgical intervention required to stabilize the ankle
- Unable to read and understand the consent form
- Unable to meet the needs of the follow-up examinations
- Allergic to the betamethasone
- Current fungal infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bupivacaine hydrochloride and betamethasone sodium phosphateAlso: Marcaine, Celestone, Soluspan,5ml of 0.25% bupivacaine hydrochloride and 2 ml of 3mg/ml betamethasone sodium phosphate one injection into the inferior tibiofibular ligament | Drug | bupivacaine hydrochloride and betamethasone sodium phosphate |
| bupivacaine hydrochlorideAlso: Marcaine5ml of bupivacaine hydrochloride into the tibiofibular ligament | Drug | bupivacaine hydrochloride |
Primary outcome
Compare Between the Two Groups the Time to Return to Previous Levels of Activity
Time frame: One year
1 secondary outcome
Compare Patient Reported Outcomes Between the Two Groups Using the Foot and Ankle Ability Measure (FAAM) Tool.
Time frame: One year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23339895Hunt KJ, George E, Harris AH, Dragoo JL. Epidemiology of syndesmosis injuries in intercollegiate football: incidence and risk factors from National Collegiate Athletic Association injury surveillance system data from 2004-2005 to 2008-2009. Clin J Sport Med. 2013 Jul;23(4):278-82. doi: 10.1097/JSM.0b013e31827ee829.
- Background: PubMed 2113510Hopkinson WJ, St Pierre P, Ryan JB, Wheeler JH. Syndesmosis sprains of the ankle. Foot Ankle. 1990 Jun;10(6):325-30. doi: 10.1177/107110079001000607.
- Background: PubMed 15572325Wright RW, Barile RJ, Surprenant DA, Matava MJ. Ankle syndesmosis sprains in national hockey league players. Am J Sports Med. 2004 Dec;32(8):1941-5. doi: 10.1177/0363546504264581.
- Background: PubMed 6642626Katznelson A, Lin E, Militiano J. Ruptures of the ligaments about the tibio-fibular syndesmosis. Injury. 1983 Nov;15(3):170-2. doi: 10.1016/0020-1383(83)90007-4.
- Background: PubMed 11206253Nussbaum ED, Hosea TM, Sieler SD, Incremona BR, Kessler DE. Prospective evaluation of syndesmotic ankle sprains without diastasis. Am J Sports Med. 2001 Jan-Feb;29(1):31-5. doi: 10.1177/03635465010290011001.
- Background: PubMed 15712981Cole BJ, Schumacher HR Jr. Injectable corticosteroids in modern practice. J Am Acad Orthop Surg. 2005 Jan-Feb;13(1):37-46. doi: 10.5435/00124635-200501000-00006.
- Background: PubMed 19336613Mei-Dan O, Kots E, Barchilon V, Massarwe S, Nyska M, Mann G. A dynamic ultrasound examination for the diagnosis of ankle syndesmotic injury in professional athletes: a preliminary study. Am J Sports Med. 2009 May;37(5):1009-16. doi: 10.1177/0363546508331202. Epub 2009 Mar 31.
- Background: PubMed 24938396Laver L, Carmont MR, McConkey MO, Palmanovich E, Yaacobi E, Mann G, Nyska M, Kots E, Mei-Dan O. Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in elite athletes: a randomized control trial. Knee Surg Sports Traumatol Arthrosc. 2015 Nov;23(11):3383-92. doi: 10.1007/s00167-014-3119-x. Epub 2014 Jun 18.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce Piatt, MD principal investigator
Orthopedic Surgeon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bupivacaine hydrochloride and betamethasone sodium phosphate and bupivacaine hydrochloride in people with Ankle Injuries, run by Sanford Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare Between the Two Groups the Time to Return to Previous Levels of Activity (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02892500, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2024.