Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial (LiFT)

Study Overview
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Brief Summary
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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
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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).

Official Title
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Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial

Conditions
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Fractures

Intervention / Treatment
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* Drug: Lithium Carbonate
* Drug: Lactose Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-55 years. ASA (American Society of Anesthesiologists) ≤ 2 class (healthy) prior to injury. 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. Fracture that is primarily closed or open fracture that has complete wound coverage. Randomization ≤14 days from injury or surgery (for surgical patients). Fractures treated surgically or nonsurgically by endochondral/secondary bone healing. For surgical patients, surgery must be within 14 days of injury. Exclusion Criteria: Currently pregnant or breastfeeding. Any past or current malignancy that, in the opinion of an investigator, is not medically controlled. Metabolic bone disease based on clinical history that, in the opinion of an investigator, is not medically controlled. Autoimmune disease that, in the opinion of an investigator, is not medically controlled. Hypothyroidism based on clinical history that, in the opinion of an investigator, is not medically controlled. Renal impairment based on clinical history. Past allergy or adverse reaction to Lithium. Lactose intolerance. Fractures surgically treated with absolute stability/primary bone healing. Isolated tibia or isolated fibula fracture. Currently taking Lithium or anti-psychotic or anti-seizure medication for the treatment of these conditions or at the discretion of an investigator. Inability to comply with study protocol, in the opinion of the investigator(s). Participation in another interventional clinical trial, at the discretion of the principal investigator. Use of concomitant ultrasound or other bone stimulation device.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lithium carbonate<br>Lithium carbonate 300mg capsule; once per day for 2 weeks. | Drug: Lithium Carbonate<br>* Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.<br>* Other names: Lithium;|
| Placebo Comparator: Lactose placebo<br>Lactose placebo capsule; once per day for 2 weeks. | Drug: Lactose Placebo<br>* Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radiographic healing of fracture | radiographic healing using the RUST score at 8 weeks | 8 weeks after injury (non-surgical participants) or 8 weeks after surgery (surgical participants) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radiographic union of fracture | time to radiographic union using the RUST score | 4, 6, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 12, and 24 weeks after surgery (surgical participants) | 
| visual analogue pain score | changes from baseline in participant-reported average pain in past week as measured on a visual analogue scale from 0-10 where 0 is no pain and 10 is extreme pain | 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) | 
| physical function | changes in participant-reported function from baseline as measured on the RAND SF36 questionnaire | 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) | 
| NSAID use | to track participant-reported use of non-steroidal anti-inflammatory medication and measure changes over the course of the study | 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) | 
| re-operation (after initial fracture management) | surgery required after initial fracture management | 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 8, 12, and 24 weeks after surgery (surgical participants) | 
| adverse events | the number and type of adverse events occuring after the first dose of lithium/placebo and until the 6-week visit will be collected and reported according to local and national rules and regulations | 2-6 weeks after injury (non-surgical participants) or 2-6 weeks after surgery (surgical participants) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone fractures, bony callus, fractures, bone, lithium, lithium carbonate, osteogenesis, bone development, fracture healing, fracture repair