Lithium for Broken Bones

(LiFT Trial)

Recruiting at 4 trial locations

Overseen By Mariam Saleem

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Lithium, Antipsychotics, Antiseizure

Disqualifiers: Pregnancy, Cancer, Renal impairment, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a low dose of Lithium, taken for two weeks, can enhance bone healing and improve daily functioning. Participants will receive either Lithium Carbonate or a placebo to compare effects. It targets individuals with a specific type of arm, leg, or collarbone fracture sustained within the last two weeks, treated surgically or non-surgically. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking Lithium, anti-psychotic, or anti-seizure medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lithium carbonate, a medication often used for mood disorders, might also benefit bone health. Studies have found that people taking lithium have a lower chance of breaking bones. Specifically, one study showed a 25% reduction in fracture risk for those currently using lithium.

Regarding safety, the FDA has already approved lithium for treating bipolar disorder, indicating it is generally safe. However, like any medication, it can cause side effects, such as increased thirst, weight gain, or mild shaking. The low dose used in this trial, taken for just two weeks, is expected to reduce these risks. Always discuss any concerns with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for broken bones?

Lithium carbonate is unique because it's typically known for treating mood disorders, but researchers are exploring its potential to accelerate bone healing. Unlike standard treatments for broken bones, which primarily focus on immobilization and pain management, lithium carbonate might enhance bone regeneration at a cellular level. This novel approach could lead to faster recovery times, making it an exciting potential addition to the treatment landscape for fractures.

What evidence suggests that lithium carbonate might be an effective treatment for fracture healing?

Research has shown that lithium carbonate, which participants in this trial may receive, might aid in healing broken bones. One study found that people taking lithium had a 25% lower chance of fractures compared to those who did not take it. This suggests lithium could strengthen bones or assist in their healing. Many people are willing to try lithium for bone healing, especially if the dose is low or the treatment is brief. Although lithium is typically used to treat bipolar disorder, these findings suggest it might also assist in healing broken bones. ^{1 2 3 6 7}

Who Is on the Research Team?

Diane Nam, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

The LiFT trial is for healthy adults aged 18-55 with certain types of broken bones (humerus, femur, tibia/fibula, clavicle) that can heal on their own or after surgery. Participants must not have uncontrolled diseases like cancer or autoimmune disorders, be pregnant/breastfeeding, lactose intolerant, have renal issues or past bad reactions to Lithium.

Inclusion Criteria

My fracture is either fully closed or, if open, the wound is completely covered.

I was injured or had surgery less than 14 days ago.

I have a mid-shaft fracture in my arm, leg, or collarbone, possibly with nerve damage.

Exclusion Criteria

Participation in another interventional clinical trial, at the discretion of the principal investigator

I am currently on Lithium, anti-psychotic, or anti-seizure medication.

Lactose intolerance

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either lithium or placebo capsules daily for 2 weeks, starting 2 weeks after fracture or surgery

2 weeks

Daily administration

Follow-up

Participants are monitored for safety, effectiveness, and adverse events after treatment

24 weeks

Visits at 3, 4, 6, 8, 12, and 24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lactose Placebo
• Lithium Carbonate

Trial Overview This study tests if a low dose of Lithium Carbonate over two weeks helps bone fractures heal better compared to a Lactose Placebo. It's double-blind meaning neither the patients nor the researchers know who gets the real treatment versus placebo until after results are collected.

How Is the Trial Designed?

Group I: Lithium carbonate Experimental Treatment 1 Intervention

Lithium carbonate 300mg capsule; once per day for 2 weeks.

Group II: Lactose placebo Placebo Group 1 Intervention

Lactose placebo capsule; once per day for 2 weeks.

Lithium Carbonate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Lithium Carbonate for:

• Bipolar disorder

Approved in United States as Lithium Carbonate for:

• Bipolar disorder

Approved in Canada as Lithium Carbonate for:

• Bipolar disorder

Approved in Japan as Lithium Carbonate for:

• Bipolar disorder

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

A survey identified 33 cases of chemistry set poisoning in children, with one fatality and 13 recoveries, highlighting the significant risk associated with these sets, particularly due to inadequate packaging that was not child-resistant.

The study revealed that 42% of poisoning cases were linked to copper sulphate, and it led to recommendations for improved safety measures, including child-resistant containers and legal restrictions on toxic chemicals in chemistry sets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemistry set poisoning. Mucklow, ES.[2015]

The study successfully synthesized lithium-silicate glass with 10 mol% Li2O using two different lithium precursors, lithium citrate and lithium nitrate, which resulted in distinct glass structures and properties.

Both types of synthesized materials (glass and glass-ceramic) were found to be safe for chondrocyte cells, showing no negative effects on cell viability or proliferation, making them promising candidates for cartilage regeneration applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium-silicate sol-gel bioactive glass and the effect of lithium precursor on structure-property relationships. Maçon, ALB., Jacquemin, M., Page, SJ., et al.[2022]

Lithium-doped biphasic calcium phosphate (BCP) can enhance the osteogenic properties of the material, with the optimal doping level identified as approximately 10 at%, which improves biological responses without causing instability.

Higher concentrations of lithium ions (above 10 at%) lead to crystal instability and do not further enhance the osteogenic behavior of human dental pulp stem cells, highlighting the importance of finding the right balance in lithium doping for effective medical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium doped biphasic calcium phosphate: Structural analysis and osteo/odontogenic potential in vitro. Yoo, KH., Kim, Y., Kim, YI., et al.[2022]

Certain substances, including antimalarials and sulfonylureas, can cause serious and potentially fatal poisonings in toddlers even in small doses.

Early recognition and prompt management, including the use of antidotes and supportive care, are crucial in preventing severe outcomes from these poisonings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One pill can kill: assessing the potential for fatal poisonings in children. Matteucci, MJ.[2019]

This systematic report on Kudiezi injection compiles evidence from quality control, premarketing safety experiments, and postmarketing efficacy studies to assess its safety and effectiveness in clinical use.

The analysis aims to provide a comprehensive understanding of Kudiezi injection, highlighting the need for further research to ensure its safe application in medical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Systematic report on re-evaluating kudiezi injection]. Liao, X., Hua, GQ., Xie, YM., et al.[2014]

In a study of 41 patients treated with colchicine over 20 years, 63.4% experienced either a complete response or improvement in their skin disease, indicating its efficacy.

Colchicine was found to have a favorable safety profile, with adverse events occurring rarely among the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of colchicine in inflammatory skin diseases: a retrospective, monocentric study in a large tertiary center. Anzengruber, F., Graf, V., Hafner, J., et al.[2021]

In a study involving 20 female rats with tibial bone defects, the lithium chloride-doped calcium phosphate cement (Li/CPC) significantly improved bone repair compared to the control cement, showing higher new bone volume and better structural integrity.

Li/CPC not only promoted faster bone healing, as evidenced by earlier formation of bone tissue, but also demonstrated superior osteoinductive properties, making it a promising option for enhancing bone defect repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of a lithium-doped calcium phosphate cement in promoting tibial bone defect repair in rats]. Li, L., Qin, YB., Ma, G., et al.[2018]

In a study involving 10 female Wistar rats over 3 months, lithium carbonate was found to cause bone loss, indicating potential negative effects on bone health.

The study suggests that patients on long-term lithium therapy should be closely monitored for bone health, especially if they have additional risk factors for osteopenia, such as menopause or low calcium intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of lithium carbonate on subchondral bone in sexually mature Wistar rats. Lewicki, M., Paez, H., Mandalunis, PM.[2013]

Lithium chloride (LiCl) significantly improved bone filling around titanium implants in estrogen-deficient rats, showing better results compared to the estrogen-deficient group at 20 and 30 days after implant placement.

In vitro, LiCl enhanced osteoblast-like cell activity by increasing mineralization and the expression of bone-related genes, indicating its potential to promote bone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium chloride improves bone filling around implants placed in estrogen-deficient rats. Posch, AT., de Avellar-Pinto, JF., Malta, FS., et al.[2020]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6955565/

Lithium for Fracture Treatment (LiFT): a double-blind ... Fracture healing can fail in up to 10% of cases despite appropriate treatment. While lithium has been the standard treatment for bipolar ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S8756328206009203

Lithium use and the risk of fractures Our results show a decreased risk of fractures in current lithium users (adjusted OR = 0.75, 95% CI = 0.64–0.88). Duration of use did not substantially change ...

3. bmjopen.bmj.com bmjopen.bmj.com/content/10/1/e031545.reviewer-comments

Lithium for Fracture Treatment (LiFT) Fracture healing after 6 months is not the focus of this current study, as the protocol is designed to first demonstrate lithium's efficacy to ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31470828/

Perceptions of using lithium in fracture management Of these, 40% were willing to take lithium for fracture healing with an additional 10% if the dose was low or if the intake duration was short.

5. withpower.com withpower.com/trial/phase-3-fractures-bone-6-2017-baf72

Lithium for Broken Bones (LiFT Trial) Trial Overview This study tests if a low dose of Lithium Carbonate over two weeks helps bone fractures heal better compared to a Lactose Placebo. It's double- ...

6. researchgate.net researchgate.net/publication/328589477_Lithium_use_and_risk_of_fracture_a_systematic_review_and_meta-analysis_of_observational_studies

Lithium use and risk of fracture: a systematic review and ... In conclusion, our results suggest that maintenance therapy with lithium carbonate may preserve or enhance bone mass. These data also suggest a lower bone ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01108068

Trial of Lithium Carbonate for Treatment of Osteoporosis ... In the mouse model of OPPG, lithium dramatically improved their bones, returning them to normal strength and preventing fractures. Lithium, which is used for ...