Investigations of Mechanisms and Treatment in Post-traumatic Joint Contractures (Ketotifen)
Primary Purpose
Joint Contractures
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Ketotifen
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Joint Contractures focused on measuring Joint, Contracture, Elbow, Fracture, Dislocation
Eligibility Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Peter Lougheed Centre
- Foothills Medical Centre
- South Health Campus
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Arm Label
Operative, Ketotifen
Non-operative, Ketotifen
Operative, Placebo
Non-operative, Placebo
Arm Description
Ketotifen 5mg orally twice per day for 6 weeks.
Ketotifen 5mg orally twice per day for 6 weeks.
Placebo oral medication twice daily for 6 weeks.
Placebo oral medication twice daily for 6 weeks.
Outcomes
Primary Outcome Measures
Joint range of motion
Extension-flexion arc of motion
Secondary Outcome Measures
Range of motion
Patients requiring (re)operation for elbow-related causes
Radiographic evaluation for fracture healing/non-union
Full Information
NCT ID
NCT01902017
First Posted
July 10, 2013
Last Updated
March 25, 2018
Sponsor
University of Calgary
Collaborators
Canadian Institutes of Health Research (CIHR), American Society for Surgery of the Hand, Workers' Compensation Board, Alberta
1. Study Identification
Unique Protocol Identification Number
NCT01902017
Brief Title
Investigations of Mechanisms and Treatment in Post-traumatic Joint Contractures
Acronym
Ketotifen
Official Title
Randomized, Double Blind, Placebo Controlled Trial of Ketotifen in Patients With Elbow Fractures or Dislocations
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
August 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary
Collaborators
Canadian Institutes of Health Research (CIHR), American Society for Surgery of the Hand, Workers' Compensation Board, Alberta
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Joint Contractures
Keywords
Joint, Contracture, Elbow, Fracture, Dislocation
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
152 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Operative, Ketotifen
Arm Type
Experimental
Arm Description
Ketotifen 5mg orally twice per day for 6 weeks.
Arm Title
Non-operative, Ketotifen
Arm Type
Experimental
Arm Description
Ketotifen 5mg orally twice per day for 6 weeks.
Arm Title
Operative, Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo oral medication twice daily for 6 weeks.
Arm Title
Non-operative, Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo oral medication twice daily for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Ketotifen
Other Intervention Name(s)
Zaditen
Intervention Description
5 mg PO bid
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Lactose Placebo
Intervention Description
5 mg placebo PO bid
Primary Outcome Measure Information:
Title
Joint range of motion
Description
Extension-flexion arc of motion
Time Frame
12 months post-injury
Secondary Outcome Measure Information:
Title
Range of motion
Time Frame
2,6,12,24 and 52 weeks post injury
Title
Patients requiring (re)operation for elbow-related causes
Time Frame
12 months
Title
Radiographic evaluation for fracture healing/non-union
Time Frame
12-52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kevin Hildebrand, MD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peter Lougheed Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T1Y 6J4
Country
Canada
Facility Name
Foothills Medical Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 1N4
Country
Canada
Facility Name
South Health Campus
City
Calgary
State/Province
Alberta
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
32112583
Citation
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.
Results Reference
background
PubMed Identifier
32639394
Citation
Hildebrand 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.
Results Reference
derived
Learn more about this trial
Investigations of Mechanisms and Treatment in Post-traumatic Joint Contractures
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