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

Phase 2

Recruiting

• Conditions: Fractures
• Interventions: Drug: Lithium Carbonate; Drug: Lactose Placebo

• Registration Number: NCT02999022
• Lead Sponsor: Sunnybrook Health Sciences Centre

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).

Study Timeline

• Study First Submitted: 2016-09-09
• Study First Submitted QC: 2016-12-16
• Study First Posted: 2016-12-21
• Study Start: 2017-07-21
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-25
• Last Update Posted: 2024-01-26
• Primary Completion: 2024-12
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 160

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lithium carbonate	Lithium Carbonate	Lithium carbonate 300mg capsule; once per day for 2 weeks.
Lactose placebo	Lactose Placebo	Lactose placebo capsule; once per day for 2 weeks.

Primary Outcome Measures

Name	Time	Method
radiographic healing of fracture	8 weeks after injury (non-surgical participants) or 8 weeks after surgery (surgical participants)	radiographic healing using the RUST score at 8 weeks

Secondary Outcome Measures

Name	Time	Method
radiographic union of fracture	4, 6, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 12, and 24 weeks after surgery (surgical participants)	time to radiographic union using the RUST score
visual analogue pain score	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)	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
NSAID use	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)	to track participant-reported use of non-steroidal anti-inflammatory medication and measure changes over the course of the study
adverse events	2-6 weeks after injury (non-surgical participants) or 2-6 weeks after surgery (surgical participants)	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
physical function	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)	changes in participant-reported function from baseline as measured on the RAND SF36 questionnaire
re-operation (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)	surgery required after initial fracture management

Trial Locations

Locations (5)

The Ottawa Hospital Civic Campus; 🇨🇦 Ottawa, Ontario, Canada

Royal Victoria Regional Health Centre; 🇨🇦 Barrie, Ontario, Canada

Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Unity Health St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada