Joint ContracturesPhase 2KetotifenNCT01902017
Investigations of Mechanisms and Treatment in Post-traumatic Joint Contractures
A Phase 2 study testing Ketotifen in people with Joint Contractures, run by University of Calgary at 3 sites in Canada.
Trial summary
Injured joints, especially at the elbow, are at risk for permanent motion loss, also known as joint contractures. Joint contractures limit the function of an elbow and are a recognized complication that occurs often after a traumatic injury. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Joint Contractures
- What is being tested?
- Ketotifen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 152 participants
- Where
- 3 sitesCanada
- Study dates
- Jun 2013to Aug 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old
- Isolated distal 1/3 humerus fractures
- Proximal 1/3 ulna fractures
- Proximal 1/3 radial fractures
- Elbow dislocations
- Open fractures with or without nerve injury
- Presentation to Peter Lougheed Centre (PLC), Foothills Medical Centre (FMC) or South Health Campus (SHC).
Who cannot join
- Pre-existing elbow contracture
- Osteoarthritis of affected elbow
- Inflammatory arthritis of affected elbow
- Gout of affected elbow
- Nonspecific monoarticular arthritis of the affected elbow
- Inability to give informed consent due to irreversible cognitive disorder
Show all 14Show fewer
- Inability to comply with post-operative physiotherapy
- Injury > 7 days at the time of presentation
- Inability to mobilize elbow injury within 2 weeks of injury or surgery
- Pregnancy
- Breast feeding
- Oral hypoglycemic medications
- History of epilepsy
- Lactose intolerance
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4
Foothills Medical Centre
Calgary, Alberta, T2N 1N4
South Health Campus
Calgary, Alberta
About this study
Official title: Randomized, Double Blind, Placebo Controlled Trial of Ketotifen in Patients With Elbow Fractures or Dislocations
Injured joints, especially at the elbow, are at risk for permanent motion loss, also known as joint contractures. Joint contractures limit the function of an elbow and are a recognized complication that occurs often after a traumatic injury. The benefits of early motion after injury has helped in preventing joint contractures but there are still several patients that develop debilitating joint contractures. Current research suggests that mast cells, which are found in the joint, are key in causing joint contractures. Research has been done using a medication called Ketotifen. Ketotifen has been linked to stabilizing mast cells and preventing the joint contracture. It is hoped that short-term use of this medication after an injury will prevent the contracture from occurring.
Read the detailed description
Individuals ≥ 18 years old with isolated distal 1/3 humerus and/or proximal 1/3 ulna and/or proximal 1/3 radius fractures and/or elbow dislocations (open fractures with or without nerve injury may be included) and presented to Peter Lougheed Centre (PLC), Foothills Medical Center (FMC), or South Health Campus (SHC).
Participants were required to take Ketotifen 5mg by mouth twice a day for 6 weeks or placebo twice a day by mouth for 6 weeks. Neither the participant nor the physician knew if the participant was taking Ketotifen or placebo. Sometimes this type of injury requires surgery. This study invited both patients that do and do not require surgery to participate.
We took a sample of blood to measure tryptase (normally found in the body). We predicted people with high levels of tryptase were more likely to develop stiffening in the joint.
Participants were asked to return for follow up visits 2, 6, 12, 24, and 52 weeks after surgery or date of initial injury if surgery was not required. These visits were part of normal care for this type of injury.
At the visit participants were asked to do the following, some of which was not part of normal care.
At each visit: Range of motion of the elbow was assessed, DASH score was completed- form helping the research group understand the level of disability from this injury, X-rays until the fracture was considered healed (this was normal treatment), SF12 - questionnaire about how the patient was feeling and coping with their injury, Additional information was collected about how the injury was healing and weight was measured.
The participant was required to have physiotherapy which is normal treatment for this injury.
The participant was contacted by telephone at week 1, 3, 4 and 5 while taking the study medication. During these times:
The participant was asked about:
- any problems with the study medication
- any new conditions or concerns that have developed
The participant was reminded:
- of next visit
- to continue to take study drug as instructed
During these telephone contacts, if any problems were detected that could not be rectified or figured out during the telephone interview, then participant was asked to attend the Cast Clinic to see their doctor in person.
- Conditions
- Joint Contractures
- Being tested
- Ketotifen, Placebo
- Keywords
- Joint, Contracture, Elbow, Fracture, Dislocation
- Medical subject headings
- Contracture, Fractures, Bone, Joint Dislocations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetotifenDrug
Also called Zaditen
5 mg PO bid
PlaceboDrug
Also called Lactose Placebo
5 mg placebo PO bid
| Study group | Role | What they receive |
|---|---|---|
| Operative, Ketotifen | Experimental | Ketotifen 5mg orally twice per day for 6 weeks. Receives: Drug: Ketotifen |
| Non-operative, Ketotifen | Experimental | Ketotifen 5mg orally twice per day for 6 weeks. Receives: Drug: Ketotifen |
| Operative, Placebo | Placebo comparator | Placebo oral medication twice daily for 6 weeks. Receives: Drug: Placebo |
| Non-operative, Placebo | Placebo comparator | Placebo oral medication twice daily for 6 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Joint range of motion
Extension-flexion arc of motion
Measured: 12 months post-injury
Secondary outcomes (3)
Range of motion
Measured: 2,6,12,24 and 52 weeks post injury
Patients requiring (re)operation for elbow-related causes
Measured: 12 months
Radiographic evaluation for fracture healing/non-union
Measured: 12-52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2013 (estimated)
- Study startJun 2013
- Primary completionAug 2017
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Joint ContracturesStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), American Society for Surgery of the Hand, Workers' Compensation Board, Alberta
- Responsible party
- Principal investigator, Dr. Kevin Hildebrand, University of Calgary
- Investigators
- Kevin Hildebrand, MD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01902017
- Sponsor's protocol ID
- REB15-0081
- Other IDs
- REB15-0081
- Acronym
- Ketotifen
- Status last verified
- Mar 2018
- First submitted
- 10 Jul 2013
- Last updated
- 27 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Liu CS, Ademola A, Zhang M, Garven A, Kopka M, Salo PT, Hart DA, Befus AD, Hildebrand KA. Human serum mast cell tryptase levels in elbow fractures or dislocations and its association with injury severity. J Orthop Res. 2020 Sep;38(9):2015-2019. doi: 10.1002/jor.24642. Epub 2020 Mar 11.
PubMed 32112583Hildebrand KA, Schneider PS, Mohtadi NGH, Ademola A, White NJ, Garven A, Walker REA, Sajobi TT; PERK 1 Investigators. PrEvention of Posttraumatic contractuRes with Ketotifen 1 (PERK 1): A Randomized Clinical Trial. J Orthop Trauma. 2020 Dec 1;34(12):e442-e448. doi: 10.1097/BOT.0000000000001878.
PubMed 32639394
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double Blind, Placebo Controlled Trial of Ketotifen in Patients With Elbow Fractures or Dislocations
- ClinicalTrials.gov ID
- NCT01902017
- Acronym / sponsor ID
- Ketotifen / REB15-0081
- Conditions
- Joint Contractures
- Keywords
- Joint, Contracture, Elbow, Fracture, Dislocation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 152 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), American Society for Surgery of the Hand, Workers' Compensation Board, Alberta
- Study start
- Jun 2013
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 17 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Injured joints, especially at the elbow, are at risk for permanent motion loss, also known as joint contractures. Joint contractures limit the function of an elbow and are a recognized complication that occurs often after a traumatic injury. The benefits of early motion after injury has helped in preventing joint contractures but there are still several patients that develop debilitating joint contractures. Current research suggests that mast cells, which are found in the joint, are key in causing joint contractures. Research has been done using a medication called Ketotifen. Ketotifen has been linked to stabilizing mast cells and preventing the joint contracture. It is hoped that short-term use of this medication after an injury will prevent the contracture from occurring.
Detailed description
Individuals ≥ 18 years old with isolated distal 1/3 humerus and/or proximal 1/3 ulna and/or proximal 1/3 radius fractures and/or elbow dislocations (open fractures with or without nerve injury may be included) and presented to Peter Lougheed Centre (PLC), Foothills Medical Center (FMC), or South Health Campus (SHC).
Participants were required to take Ketotifen 5mg by mouth twice a day for 6 weeks or placebo twice a day by mouth for 6 weeks. Neither the participant nor the physician knew if the participant was taking Ketotifen or placebo. Sometimes this type of injury requires surgery. This study invited both patients that do and do not require surgery to participate.
We took a sample of blood to measure tryptase (normally found in the body). We predicted people with high levels of tryptase were more likely to develop stiffening in the joint.
Participants were asked to return for follow up visits 2, 6, 12, 24, and 52 weeks after surgery or date of initial injury if surgery was not required. These visits were part of normal care for this type of injury.
At the visit participants were asked to do the following, some of which was not part of normal care.
At each visit: Range of motion of the elbow was assessed, DASH score was completed- form helping the research group understand the level of disability from this injury, X-rays until the fracture was considered healed (this was normal treatment), SF12 - questionnaire about how the patient was feeling and coping with their injury, Additional information was collected about how the injury was healing and weight was measured.
The participant was required to have physiotherapy which is normal treatment for this injury.
The participant was contacted by telephone at week 1, 3, 4 and 5 while taking the study medication. During these times:
The participant was asked about:
- any problems with the study medication
- any new conditions or concerns that have developed
The participant was reminded:
- of next visit
- to continue to take study drug as instructed
During these telephone contacts, if any problems were detected that could not be rectified or figured out during the telephone interview, then participant was asked to attend the Cast Clinic to see their doctor in person.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Operative, Ketotifen | Experimental | Drug: KetotifenKetotifen 5mg orally twice per day for 6 weeks. |
| Non-operative, Ketotifen | Experimental | Drug: KetotifenKetotifen 5mg orally twice per day for 6 weeks. |
| Operative, Placebo | Placebo comparator | Drug: PlaceboPlacebo oral medication twice daily for 6 weeks. |
| Non-operative, Placebo | Placebo comparator | Drug: PlaceboPlacebo oral medication twice daily for 6 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 18 years old
- Isolated distal 1/3 humerus fractures
- Proximal 1/3 ulna fractures
- Proximal 1/3 radial fractures
- Elbow dislocations
Key exclusion criteria (14 listed)
- Pre-existing elbow contracture
- Osteoarthritis of affected elbow
- Inflammatory arthritis of affected elbow
- Gout of affected elbow
- Nonspecific monoarticular arthritis of the affected elbow
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 |
|---|---|---|
| KetotifenAlso: Zaditen5 mg PO bid | Drug | Non-operative, Ketotifen, Operative, Ketotifen |
| PlaceboAlso: Lactose Placebo5 mg placebo PO bid | Drug | Non-operative, Placebo, Operative, Placebo |
Primary outcome
Joint range of motion
Time frame: 12 months post-injury
Extension-flexion arc of motion
3 secondary outcomes
Range of motion
Time frame: 2,6,12,24 and 52 weeks post injury
Patients requiring (re)operation for elbow-related causes
Time frame: 12 months
Radiographic evaluation for fracture healing/non-union
Time frame: 12-52 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2018.
- Background: PubMed 32112583Liu CS, Ademola A, Zhang M, Garven A, Kopka M, Salo PT, Hart DA, Befus AD, Hildebrand KA. Human serum mast cell tryptase levels in elbow fractures or dislocations and its association with injury severity. J Orthop Res. 2020 Sep;38(9):2015-2019. doi: 10.1002/jor.24642. Epub 2020 Mar 11.
- Derived from this study: PubMed 32639394Hildebrand KA, Schneider PS, Mohtadi NGH, Ademola A, White NJ, Garven A, Walker REA, Sajobi TT; PERK 1 Investigators. PrEvention of Posttraumatic contractuRes with Ketotifen 1 (PERK 1): A Randomized Clinical Trial. J Orthop Trauma. 2020 Dec 1;34(12):e442-e448. doi: 10.1097/BOT.0000000000001878.
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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.
Kevin Hildebrand, MD principal investigator
University of Calgary
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketotifen in people with Joint Contractures, run by University of Calgary at 3 sites in Canada.
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 7 inclusion and 14 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: finished, as of the sponsor's last update on 27 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Joint range of motion (time frame: 12 months post-injury). 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 NCT01902017, which also lists 2 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 27 Mar 2018.