<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02999022</url>
  </required_header>
  <id_info>
    <org_study_id>LiFT001</org_study_id>
    <nct_id>NCT02999022</nct_id>
  </id_info>
  <brief_title>Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial (LiFT)</brief_title>
  <acronym>LiFT</acronym>
  <official_title>Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sunnybrook Health Sciences Centre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study designed to see if a low dose of Lithium treatment, taken for 2 weeks, can&#xD;
      improve fracture healing and improve patients' function and productivity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite the success of traditional treatments for broken bones (surgery, immobilization, or&#xD;
      both) 10% of fractures do not heal or take longer than normal to heal. This can have a&#xD;
      significant effect on a patient's function and productivity, as well as on healthcare&#xD;
      expenditures. Very few advances in fracture healing have been made, despite the need for new&#xD;
      approaches to fracture treatment. This study proposes a simple, economical, and non-invasive&#xD;
      approach to complement traditional fracture treatment that could decrease healing time and&#xD;
      reduce the incidence of delayed healing. The investigators think that this can improve health&#xD;
      outcomes for patients and reduce health care costs for the healthcare system in general. The&#xD;
      goal is to see if a low-dose of Lithium treatment can have a positive effect on fracture&#xD;
      healing and can reduce pain and improve function in patients who have broken a bone.&#xD;
&#xD;
      The LiFT study is a participant, surgeon and observer blinded single-centre randomized (1:1),&#xD;
      controlled, superiority trial with 2 parallel groups. A minimization procedure will stratify&#xD;
      participants based on the fractured long bone (clavicle, humerus, femur or tibia/fibula) and&#xD;
      smoking.&#xD;
&#xD;
      Participants will be randomized to 1 of 2 groups: lithium capsules or placebo. The&#xD;
      Lithium/placebo will be taken daily for 2 weeks, starting 2 weeks after the fracture occurs&#xD;
      (or 2 weeks after surgery if the participant is treated with surgery).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 21, 2017</start_date>
  <completion_date type="Anticipated">June 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>radiographic healing of fracture</measure>
    <time_frame>8 weeks after injury (non-surgical participants) or 8 weeks after surgery (surgical participants)</time_frame>
    <description>radiographic healing using the RUST score at 8 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>radiographic union of fracture</measure>
    <time_frame>4, 6, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 12, and 24 weeks after surgery (surgical participants)</time_frame>
    <description>time to radiographic union using the RUST score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>visual analogue pain score</measure>
    <time_frame>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)</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>physical function</measure>
    <time_frame>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)</time_frame>
    <description>changes in participant-reported function from baseline as measured on the RAND SF36 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NSAID use</measure>
    <time_frame>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)</time_frame>
    <description>to track participant-reported use of non-steroidal anti-inflammatory medication and measure changes over the course of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>re-operation (after initial fracture management)</measure>
    <time_frame>4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 8, 12, and 24 weeks after surgery (surgical participants)</time_frame>
    <description>surgery required after initial fracture management</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>2-6 weeks after injury (non-surgical participants) or 2-6 weeks after surgery (surgical participants)</time_frame>
    <description>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</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Fractures</condition>
  <arm_group>
    <arm_group_label>Lithium carbonate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lithium carbonate 300mg capsule; once per day for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lactose placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Lactose placebo capsule; once per day for 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lithium Carbonate</intervention_name>
    <description>Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.</description>
    <arm_group_label>Lithium carbonate</arm_group_label>
    <other_name>Lithium</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lactose Placebo</intervention_name>
    <description>Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.</description>
    <arm_group_label>Lactose placebo</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-55 years.&#xD;
&#xD;
          2. ASA (American Society of Anesthesiologists) ≤ 2 class (healthy) prior to injury.&#xD;
&#xD;
          3. Diaphyseal fracture of the humerus, femur or combined tibia/fibula (OTA diaphyseal&#xD;
             subclass 2A or B), and clavicle (OTA diaphyseal subclass B1 or B2), with or without&#xD;
             nerve injury.&#xD;
&#xD;
          4. Fracture that is primarily closed or open fracture that has complete wound coverage.&#xD;
&#xD;
          5. Randomization ≤14 days from injury or surgery (for surgical patients).&#xD;
&#xD;
          6. Fractures treated surgically or nonsurgically by endochondral/secondary bone healing.&#xD;
&#xD;
          7. For surgical patients, surgery must be within 14 days of injury.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Currently pregnant or breastfeeding.&#xD;
&#xD;
          2. Any past or current malignancy that, in the opinion of an investigator, is not&#xD;
             medically controlled.&#xD;
&#xD;
          3. Metabolic bone disease based on clinical history that, in the opinion of an&#xD;
             investigator, is not medically controlled.&#xD;
&#xD;
          4. Autoimmune disease that, in the opinion of an investigator, is not medically&#xD;
             controlled.&#xD;
&#xD;
          5. Hypothyroidism based on clinical history that, in the opinion of an investigator, is&#xD;
             not medically controlled.&#xD;
&#xD;
          6. Renal impairment based on clinical history.&#xD;
&#xD;
          7. Past allergy or adverse reaction to Lithium.&#xD;
&#xD;
          8. Lactose intolerance.&#xD;
&#xD;
          9. Fractures surgically treated with absolute stability/primary bone healing.&#xD;
&#xD;
         10. Isolated tibia or isolated fibula fracture.&#xD;
&#xD;
         11. Currently taking Lithium or anti-psychotic or anti-seizure medication for the&#xD;
             treatment of these conditions or at the discretion of an investigator.&#xD;
&#xD;
         12. Inability to comply with study protocol, in the opinion of the investigator(s).&#xD;
&#xD;
         13. Participation in another interventional clinical trial, at the discretion of the&#xD;
             principal investigator.&#xD;
&#xD;
         14. Use of concomitant ultrasound or other bone stimulation device.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Diane Nam, MSc,MD,FRCSC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Health Sciences Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Pujitha Rao</last_name>
    <phone>416-480-5627</phone>
    <email>lift@sunnybrook.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sara Aman</last_name>
    <email>sara.aman@sri.utoronto.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Royal Victoria Regional Health Centre</name>
      <address>
        <city>Barrie</city>
        <state>Ontario</state>
        <zip>L4M 6M2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kelly Cruise</last_name>
      <phone>705-728-9090</phone>
      <phone_ext>45639</phone_ext>
      <email>cruisek@rvh.on.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hamilton Health Sciences</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jodi Gallant</last_name>
      <email>gallaj4@mcmaster.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital Civic Campus</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y 4E9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Steven Papp, MD</last_name>
      <phone>613-737-8899</phone>
      <phone_ext>18131</phone_ext>
      <email>spapp@toh.ca</email>
    </contact>
    <contact_backup>
      <last_name>Melanie Dodd-Moher</last_name>
      <phone>613-737-8899</phone>
      <phone_ext>19217</phone_ext>
      <email>medodd@ohri.ca</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5R 3P6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sara Aman</last_name>
      <email>sara.aman@sri.utoronto.ca</email>
    </contact>
    <contact_backup>
      <last_name>Katrine Milner, BSc</last_name>
      <phone>416-480-4285</phone>
      <email>katrine.milner@sunnybrook.ca</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>September 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>July 11, 2023</last_update_submitted>
  <last_update_submitted_qc>July 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>bone fractures</keyword>
  <keyword>bony callus</keyword>
  <keyword>fractures, bone</keyword>
  <keyword>lithium</keyword>
  <keyword>lithium carbonate</keyword>
  <keyword>osteogenesis</keyword>
  <keyword>bone development</keyword>
  <keyword>fracture healing</keyword>
  <keyword>fracture repair</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Bone</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lithium Carbonate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02999022
org study id: LiFT001
nct id: NCT02999022
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
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.
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: radiographic healing of fracture
time frame: 8 weeks after injury (non-surgical participants) or 8 weeks after surgery (surgical participants)
description: radiographic healing using the RUST score at 8 weeks
measure: radiographic union of fracture
time frame: 4, 6, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 12, and 24 weeks after surgery (surgical participants)
description: time to radiographic union using the RUST score
measure: visual analogue pain score
time frame: 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)
description: 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
measure: physical function
time frame: 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)
description: changes in participant-reported function from baseline as measured on the RAND SF36 questionnaire
measure: NSAID use
time frame: 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)
description: to track participant-reported use of non-steroidal anti-inflammatory medication and measure changes over the course of the study
measure: re-operation (after initial fracture management)
time frame: 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 8, 12, and 24 weeks after surgery (surgical participants)
description: surgery required after initial fracture management
measure: adverse events
time frame: 2-6 weeks after injury (non-surgical participants) or 2-6 weeks after surgery (surgical participants)
description: 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
arm group label: Lithium carbonate
arm group type: Experimental
description: Lithium carbonate 300mg capsule; once per day for 2 weeks.
arm group label: Lactose placebo
arm group type: Placebo Comparator
description: Lactose placebo capsule; once per day for 2 weeks.
intervention type: Drug
intervention name: Lithium Carbonate
description: Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.
arm group label: Lithium carbonate
other name: Lithium
intervention type: Drug
intervention name: Lactose Placebo
description: Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.
arm group label: Lactose placebo
other name: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Diane Nam, MSc,MD,FRCSC
role: Principal Investigator
affiliation: Sunnybrook Health Sciences Centre
last name: Pujitha Rao
phone: 416-480-5627
email: lift@sunnybrook.ca
last name: Sara Aman
email: sara.aman@sri.utoronto.ca
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Sponsor
mesh term: Fractures, Bone
mesh term: Lithium Carbonate
sharing ipd: No