Montelukast for ACL Injury

(MOCHA Trial)

Overseen By Austin Stone, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Austin V Stone

Disqualifiers: Revision procedures, Multiple ligament injuries, Depression, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 6 months

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is Montelukast generally safe for human use?

Montelukast, also known as Singulair, is generally considered safe for human use, but like any medication, it can have side effects. Some people have reported mood changes, headaches, and stomach pain. It's important to discuss any concerns with your doctor before starting the medication. ^{1 2 3 4 5}

How does the drug Montelukast differ from other treatments for ACL injury?

Montelukast is unique for ACL injury treatment because it is primarily used for asthma and allergies, working by blocking leukotrienes (chemicals in the body that cause inflammation). This is different from typical ACL treatments, which often involve surgery or physical therapy, as Montelukast offers a non-surgical, anti-inflammatory approach. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a multicenter randomized, placebo-controlled trial to assess whether a 6-month course of oral montelukast after ACL reconstruction reduces systemic markers of inflammation and biochemical and imaging biomarkers of cartilage degradation. This study will specifically target older ACL reconstruction patients with concomitant meniscal injuries as this group is at greatest risk of rapid PTOA progression. Patients will randomly be assigned to receive oral montelukast (10 mg) versus placebo daily for 6 months after surgery.

Research Team

Austin Stone, MD

Principal Investigator

University of Kentucky

Eligibility Criteria

The MOCHA trial is for people aged 25-50 who are having their first ACL reconstruction and also have a meniscus injury. It's not for those without a meniscus tear, with multiple ligament injuries needing more complex surgery, or showing signs of depression or suicidal thoughts at enrollment.

Inclusion Criteria

I am between 25 and 50 years old.

I have a concurrent meniscus injury.

I am scheduled for my first ACL surgery.

Exclusion Criteria

My surgery revealed I do not have a meniscus tear.

I am scheduled for a corrective surgery.

You have severe symptoms of depression or have thoughts of hurting yourself at the time of joining the study (scoring 15 or higher on a depression questionnaire called PHQ-9).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral montelukast (10 mg) or placebo daily for 6 months after ACL reconstruction surgery

6 months

Regular visits as per trial protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in KOOS, serum prostaglandin E2, T1rho relaxation time, and shape of the medial femoral condyle on MRI

6 months

Visits at 10 days, 4 weeks, and 1 year post-surgery

Treatment Details

Interventions

• Montelukast
• Placebo

Trial Overview This study tests if taking montelukast (10 mg) daily for 6 months after ACL surgery can lower inflammation and slow down cartilage damage compared to a placebo. Participants will be randomly chosen to get either the drug or placebo.

Participant Groups

Group I: Montelukast Experimental Treatment 1 Intervention

Patients will receive oral montelukast (10 mg) daily for 6 months after surgery.

Group II: Placebo Placebo Group 1 Intervention

Patients will receive an oral placebo daily for 6 months after surgery.

Montelukast is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Singulair for:

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Approved in Canada as Singulair for:

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Approved in European Union as Singulair for:

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Who Is Running the Clinical Trial?

Austin V Stone

Lead Sponsor

Trials

5

Recruited

70+

Cale Jacobs, PhD

Lead Sponsor

Trials

5

Recruited

140+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Findings from Research

The European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) recommends that oral Janus kinase inhibitors (JAKi) should only be used in patients aged 65 and older or those with cardiovascular disease risk factors when no suitable alternatives are available, highlighting safety concerns.

Despite these precautions, the benefit-risk profile of JAKi remains favorable for patients with atopic dermatitis under 65 years old and without cardiovascular or malignancy risk factors, allowing for their use as first-line systemic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A detailed look at the European Medicines Agency's recommendations for use of Janus kinase inhibitors in patients with atopic dermatitis. Wollenberg, A., Thyssen, JP., Bieber, T., et al.[2023]

Zafirlukast, a leukotriene inhibitor approved for asthma prevention, is generally well-tolerated with convenient dosing and few side effects.

However, there have been reports of serious side effects, including Churg-Strauss syndrome, as demonstrated in a case of a 54-year-old man who developed leukocytoclastic vasculitis, hepatitis, and eosinophilia while on zafirlukast therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasculitis induced by zafirlukast therapy. Soy, M., Ozer, H., Canataroglu, A., et al.[2021]

Long-term safety and effectiveness of TNF-alpha inhibitors are being monitored through independent, academia-initiated drug registers in several European countries, which include all licensed biological agents and utilize standardized reporting systems for adverse events.

These registers have identified key safety concerns related to infections, malignancies, cardiovascular events, and pregnancy outcomes, highlighting the importance of ongoing collaboration between regulatory authorities, academia, and pharmaceutical companies for effective pharmacovigilance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European biologicals registers: methodology, selected results and perspectives. Zink, A., Askling, J., Dixon, WG., et al.[2013]

In a study comparing the safety of Janus kinase inhibitors (JAKi) and rituximab in patients with rheumatoid arthritis and existing respiratory disorders, JAKi did not lead to a higher rate of respiratory-related hospitalizations or deaths compared to rituximab.

Among 47 patients (28 on JAKi and 19 on rituximab), the rates of respiratory events were similar, suggesting that JAKi may be a relatively safe treatment option for rheumatoid arthritis in patients with interstitial lung disease or bronchiectasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparison of respiratory events with JAK inhibitors or rituximab for rheumatoid arthritis in patients with pulmonary disease. Cronin, O., McKnight, O., Keir, L., et al.[2022]

A study analyzing adverse events (AEs) from TNFα inhibitors (adalimumab, infliximab, etanercept) in South Korea identified 5594 AEs, revealing seven new signals not previously listed on drug labels, including medication errors and thyroid neoplasm malignant.

Specific AEs were found to be significantly more likely in patients using these drugs, such as injection site pain for adalimumab and uveitis for etanercept, highlighting the need for updated drug labels to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of signal detection of tumour necrosis factor-α inhibitors using the Korea Adverse Events Reporting System Database, 2005-2016. Ha, D., Lee, SE., Song, I., et al.[2022]

A study on rat tendons showed that using vancomycin at clinically relevant concentrations (5 mg/mL for 20 minutes) does not harm cell viability or the structural integrity of tendon tissue, indicating it is safe for use in ACL reconstruction.

Even at higher concentrations and longer exposure times, vancomycin did not negatively affect gene expression related to tendon health, supporting its use as a prophylactic treatment to prevent infection without compromising tissue quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wrap It! Preventive Antimicrobial Treatment Shows No Negative Effects on Tenocytes and Tendons-A Comprehensive Approach. Thierbach, M., Müller, M., Stange, R., et al.[2023]

In a study involving 1,172 patients undergoing ACL reconstruction, soaking grafts in vancomycin (1 mg/ml) before surgery resulted in a 0% infection rate, compared to a 1.6% infection rate in patients who did not receive the antibiotic treatment.

The use of vancomycin significantly reduced the risk of postoperative infections, demonstrating its efficacy in preventing septic arthritis after ACL reconstruction, while not affecting re-rupture or arthrofibrosis rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soaking ACL grafts in vancomycin solution (1 mg/ml) reduces the infection rate without increasing the risk for re-rupture and arthrofibrosis. Hees, T., Abdelatif, Y., Karpinski, K., et al.[2022]

In a controlled laboratory study, human patellar tenocytes exposed to vancomycin at concentrations up to 12,800 μg/mL for short periods (2 and 6 hours) showed no significant decrease in cell viability, indicating low toxicity at these exposure levels.

However, after 24 hours of exposure to higher concentrations of vancomycin, there was a significant decrease in tenocyte viability, suggesting that while short-term exposure before ACL reconstruction is safe, prolonged exposure could be harmful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soaking of Autologous Tendon Grafts in Vancomycin Before Implantation Does Not Lead to Tenocyte Cytotoxicity. Xiao, M., Leonardi, EA., Sharpe, O., et al.[2021]

In a study of 22 patients with complete injuries to both the ACL and MCL, immediate arthroscopic repair of the MCL was performed while the ACL was treated non-surgically, leading to improved stability in the knee.

After an average follow-up of 2.5 years, 15 out of 22 patients showed improvement, suggesting that this treatment strategy is both safe and effective for managing combined ligament injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary reconstruction of the medial collateral ligament in combined injury of the medial collateral and anterior cruciate ligaments. Short-term results. Frölke, JP., Oskam, J., Vierhout, PA.[2016]

ACL injuries are very common among young active duty military personnel, and their treatment requires careful consideration to ensure a stable knee for optimal performance in critical situations.

The article reviews various surgical treatment options and controversies surrounding ACL surgery, aiming to provide guidelines for effective and reliable surgical outcomes tailored to the needs of physically competitive military athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Special considerations for ACL graft selection in the young, active military patient. Ryu, JH., Provencher, MT.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A detailed look at the European Medicines Agency's recommendations for use of Janus kinase inhibitors in patients with atopic dermatitis. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Vasculitis induced by zafirlukast therapy. [2021]

3. England pubmed.ncbi.nlm.nih.gov

European biologicals registers: methodology, selected results and perspectives. [2013]

4. Germany pubmed.ncbi.nlm.nih.gov

A retrospective comparison of respiratory events with JAK inhibitors or rituximab for rheumatoid arthritis in patients with pulmonary disease. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Comparison of signal detection of tumour necrosis factor-α inhibitors using the Korea Adverse Events Reporting System Database, 2005-2016. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Wrap It! Preventive Antimicrobial Treatment Shows No Negative Effects on Tenocytes and Tendons-A Comprehensive Approach. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Soaking ACL grafts in vancomycin solution (1 mg/ml) reduces the infection rate without increasing the risk for re-rupture and arthrofibrosis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Soaking of Autologous Tendon Grafts in Vancomycin Before Implantation Does Not Lead to Tenocyte Cytotoxicity. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Primary reconstruction of the medial collateral ligament in combined injury of the medial collateral and anterior cruciate ligaments. Short-term results. [2016]

10. Germany pubmed.ncbi.nlm.nih.gov

Special considerations for ACL graft selection in the young, active military patient. [2022]