Ketotifen: Investigations of Mechanisms and Treatment in Post-traumatic Joint Contractures

Sponsor

University of Calgary (Other)

Overall Status

Completed

CT.gov ID

NCT01902017

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), American Society for Surgery of the Hand (Other), Workers' Compensation Board, Alberta (Other)

152

Enrollment

Locations

Arms

Duration (Months)

50.7

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Joint Contractures	Drug: Ketotifen Drug: Placebo	Phase 2

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

Study Type:

Interventional

Actual Enrollment :

152 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Randomized, Double Blind, Placebo Controlled Trial of Ketotifen in Patients With Elbow Fractures or Dislocations

Study Start Date :

Jun 1, 2013

Actual Primary Completion Date :

Aug 1, 2017

Actual Study Completion Date :

Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Operative, Ketotifen Ketotifen 5mg orally twice per day for 6 weeks.	Drug: Ketotifen 5 mg PO bid Other Names: Zaditen
Experimental: Non-operative, Ketotifen Ketotifen 5mg orally twice per day for 6 weeks.	Drug: Ketotifen 5 mg PO bid Other Names: Zaditen
Placebo Comparator: Operative, Placebo Placebo oral medication twice daily for 6 weeks.	Drug: Placebo 5 mg placebo PO bid Other Names: Lactose Placebo
Placebo Comparator: Non-operative, Placebo Placebo oral medication twice daily for 6 weeks.	Drug: Placebo 5 mg placebo PO bid Other Names: Lactose Placebo

Outcome Measures

Primary Outcome Measures

Joint range of motion [12 months post-injury]
Extension-flexion arc of motion

Secondary Outcome Measures

Range of motion [2,6,12,24 and 52 weeks post injury]
Patients requiring (re)operation for elbow-related causes [12 months]
Radiographic evaluation for fracture healing/non-union [12-52 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).