Clinical trial NCT02999022: Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial (LiFT)
Official title: Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Fractures
Keywords: bone fractures
bony callus
fractures, bone
lithium
lithium carbonate
osteogenesis
bone development
fracture healing
fracture repair
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2016-12-21
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study designed to see if a low dose of Lithium treatment, taken for 2 weeks, can improve fracture healing and improve patients' function and productivity.

Detailed description: Despite the success of traditional treatments for broken bones (surgery, immobilization, or both) 10% of fractures do not heal or take longer than normal to heal. This can have a significant effect on a patient's function and productivity, as well as on healthcare expenditures. Very few advances in fracture healing have been made, despite the need for new approaches to fracture treatment. This study proposes a simple, economical, and non-invasive approach to complement traditional fracture treatment that could decrease healing time and reduce the incidence of delayed healing. The investigators think that this can improve health outcomes for patients and reduce health care costs for the healthcare system in general. The goal is to see if a low-dose of Lithium treatment can have a positive effect on fracture healing and can reduce pain and improve function in patients who have broken a bone.

The LiFT study is a participant, surgeon and observer blinded single-centre randomized (1:1), controlled, superiority trial with 2 parallel groups. A minimization procedure will stratify participants based on the fractured long bone (clavicle, humerus, femur or tibia/fibula) and smoking.

Participants will be randomized to 1 of 2 groups: lithium capsules or placebo. The Lithium/placebo will be taken daily for 2 weeks, starting 2 weeks after the fracture occurs (or 2 weeks after surgery if the participant is treated with surgery).

Eligibility criteria: Inclusion Criteria:

1. Age 18-55 years.
2. ASA (American Society of Anesthesiologists) ≤ 2 class (healthy) prior to injury.
3. Diaphyseal fracture of the humerus, femur or combined tibia/fibula (OTA diaphyseal subclass 2A or B), and clavicle (OTA diaphyseal subclass B1 or B2), with or without nerve injury.
4. Fracture that is primarily closed or open fracture that has complete wound coverage.
5. Randomization ≤14 days from injury or surgery (for surgical patients).
6. Fractures treated surgically or nonsurgically by endochondral/secondary bone healing.
7. For surgical patients, surgery must be within 14 days of injury.

Exclusion Criteria:

1. Currently pregnant or breastfeeding.
2. Any past or current malignancy that, in the opinion of an investigator, is not medically controlled.
3. Metabolic bone disease based on clinical history that, in the opinion of an investigator, is not medically controlled.
4. Autoimmune disease that, in the opinion of an investigator, is not medically controlled.
5. Hypothyroidism based on clinical history that, in the opinion of an investigator, is not medically controlled.
6. Renal impairment based on clinical history.
7. Past allergy or adverse reaction to Lithium.
8. Lactose intolerance.
9. Fractures surgically treated with absolute stability/primary bone healing.
10. Isolated tibia or isolated fibula fracture.
11. Currently taking Lithium or anti-psychotic or anti-seizure medication for the treatment of these conditions or at the discretion of an investigator.
12. Inability to comply with study protocol, in the opinion of the investigator(s).
13. Participation in another interventional clinical trial, at the discretion of the principal investigator.
14. Use of concomitant ultrasound or other bone stimulation device.

Primary outcomes:
measure: radiographic healing of fracture
timeFrame: 8 weeks after injury (non-surgical participants) or 8 weeks after surgery (surgical participants)
Secondary outcomes:
measure: radiographic union of fracture
timeFrame: 4, 6, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 12, and 24 weeks after surgery (surgical participants)
measure: visual analogue pain score
timeFrame: baseline then 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or baseline then 4, 6, 8, 12, and 24 weeks after surgery (surgical participants)
measure: physical function
timeFrame: baseline then 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or baseline then 4, 6, 8, 12, and 24 weeks after surgery (surgical participants)
measure: NSAID use
timeFrame: baseline then 3, 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or baseline then 3, 4, 6, 8, 12, and 24 weeks after surgery (surgical participants)
measure: re-operation (after initial fracture management)
timeFrame: 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 8, 12, and 24 weeks after surgery (surgical participants)
measure: adverse events
timeFrame: 2-6 weeks after injury (non-surgical participants) or 2-6 weeks after surgery (surgical participants)
Other outcomes:
Locations:
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Civic Campus
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Unity Health St. Michael's Hospital
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Diane Nam, MSc,MD,FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nam D, Balasuberamaniam P, Milner K, Kunz M, Vachhani K, Kiss A, Whyne C. Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol. BMJ Open. 2020 Jan 7;10(1):e031545. doi: 10.1136/bmjopen-2019-031545.