Investigations of Mechanisms and Treatment in Post-traumatic Joint Contractures

Joint Contractures Clinical Trial

— Ketotifen  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01902017
• Other study ID #: REB15-0081
• Secondary ID: REB15-0081
• Status: Completed
• Phase: Phase 2
• First received: July 10, 2013
• Last updated: March 25, 2018
• Start date: June 2013
• Est. completion date: August 2017

Study information

• Verified date: March 2018
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Contracture
• Joint Contractures

Intervention

Drug:
• Ketotifen
5 mg PO bid
• Placebo
5 mg placebo PO bid

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Peter Lougheed Centre	Calgary	Alberta
Canada	South Health Campus	Calgary	Alberta

Sponsors (4)

Lead Sponsor	Collaborator
University of Calgary	American Foundation for Surgery of the Hand, Canadian Institutes of Health Research (CIHR), Workers' Compensation Board, Alberta

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Kopka M, Zhang M, Schneider PS, Fan C-Y, Liang X, Hart DA, Befus A Dean, Garven A, Salo P, Hildebrand KA. Human Serum Mast Cell Tryptase Levels in Elbow Fractures and Dislocations. Transactions of the Orthopaedic Research Society; 41:1190, 2016.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Joint range of motion	Extension-flexion arc of motion	12 months post-injury
Secondary	Range of motion		2,6,12,24 and 52 weeks post injury
Secondary	Patients requiring (re)operation for elbow-related causes		12 months
Secondary	Radiographic evaluation for fracture healing/non-union		12-52 weeks