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

Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Fractures
• Intervention / Treatment: Drug: Lithium Carbonate; Drug: Lactose Placebo

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 Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pujitha Rao; Phone Number: 416-480-5627; Email: lift@sunnybrook.ca
• Study Contact Backup: Name: Mariam Saleem; Email: Mariam.saleem@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Recruiting
      • Royal Victoria Regional Health Centre
      • Contact: Kelly Cruise; Phone Number: 45639 705-728-9090; Email: cruisek@rvh.on.ca
      • Principal Investigator: Raaj Vora
    • Hamilton, Ontario, Canada
      • Recruiting
      • Hamilton Health Sciences
      • Contact: Jodi Gallant; Email: gallaj4@mcmaster.ca
      • Principal Investigator: Jamal Al-Asiri
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Recruiting
      • The Ottawa Hospital Civic Campus
      • Contact: Steven Papp, MD; Phone Number: 18131 613-737-8899; Email: spapp@toh.ca
      • Contact: Melanie Dodd-Moher; Phone Number: 19217 613-737-8899; Email: medodd@ohri.ca
      • Principal Investigator: Steven Papp
    • Toronto, Ontario, Canada, M5R 3P6
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: BSc
      • Contact: Katrine Milner; Phone Number: 416-480-4285; Email: katrine.milner@sunnybrook.ca
      • Principal Investigator: Diane Nam
    • Toronto, Ontario, Canada
      • Recruiting
      • Unity Health St. Michael's Hospital
      • Contact: Ashmanie Brijmohan; Email: ashmanie.brijmohan@unityhealth.ca
      • Principal Investigator: Aaron Nauth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Diane Nam, MSc,MD,FRCSC, Sunnybrook Health Sciences Centre

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2017
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: September 9, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimated): December 21, 2016

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: lithium; lithium carbonate; osteogenesis; bone fractures; bony callus; fractures, bone; bone development; fracture healing; fracture repair
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antimanic Agents; Lithium Carbonate
• Other Study ID Numbers: LiFT001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No