ACL InjuryEarly Phase 1MOCHANCT04572256
MOntelukast as a Potential CHondroprotective Treatment Following Anterior Cruciate Ligament Reconstruction (MOCHA Trial)
A Early Phase 1 study testing Montelukast in people with ACL Injury and Meniscus Tear, run by Austin V Stone at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 25 to 50 years
- Conditions the study is for
- ACL Injury, Meniscus Tear, Post-traumatic Osteoarthritis
- What is being tested?
- Montelukast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2021to Jun 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Undergoing primary ACL reconstruction
- Age between 25-50
- Concomitant meniscus injury
Who cannot join
- Undergoing revision procedures
- Multiple ligament injuries requiring multiple ligament reconstruction/repair
- Depressive symptoms and/or those who endorse suicidal ideation at the time of enrollment (PHQ-9 score >= 15)
- Found to not have a meniscus tear at the time of surgery
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UK Healthcare at Turfland
Lexington, Kentucky, 40504
Austin Stone, MD, PhD, 859-218-3065, austin.stone@uky.edu
Cale Jacobs, PhD
About this study
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.
Read the detailed description
After anterior cruciate ligament (ACL) reconstruction, patient-reported outcomes are improved 10 years post-surgery. Cytokine concentrations, however, remain elevated years after surgery; over 80% of patients with combined ACL and meniscus injuries have post-traumatic osteoarthritis (PTOA) within 10-15 years after injury. Since pain nociceptors are not located in the articular cartilage, patient-reported outcomes improve despite progressive, irreversible cartilage loss, thus making PTOA a "silent killer." Because early cartilage loss progresses without pain and dysfunction, the prevalence of PTOA continues to increase. PTOA now represents the most common cause of military disability.
Our recent results illustrate the downstream cytokine and degradative enzyme activity following ACL reconstruction. ACL and meniscus injury initiate a biochemical cascade resulting in cartilage degradation and this process involves an up-regulated pro-inflammatory response with a dysregulated anti-inflammatory response. Single-dose intra-articular anti-inflammatory treatment appears to reduce hyaline cartilage degradation shortly after the time of injury based on synovial fluid measures of type II collagen degradation. The intra-articular inflammatory milieu at the time of surgery appears to predict the patient symptom state two years later; however, the effectiveness of preoperative anti-inflammatory treatments in impacting patient symptoms or slowing long-term PTOA progression is as yet unclear. A lack of efficacy in preoperative interventions may be attributed to a profound inflammatory stimulus from surgical reconstruction of the ACL. The postoperative inflammatory cascade results in articular cartilage and meniscus degradation due to matrix degrading enzymes, especially those which breakdown type II collagen.
PTOA affects the whole joint organ including the cartilage, synovium, and bone. PTOA progression is multifaceted and includes activation of the pro-inflammatory Nuclear Factor Kappa-B (NFkB) pathway, an increase in pro-inflammatory M1 macrophages, cell senescence, and bone remodeling. Limiting the biochemical cascade through an innovative disease modifying treatment to target upstream activity will potentially treat all components of the knee, thereby lessening the inflammatory response, reducing cartilage catabolism, and potentially improving pathologic bony remodeling observed after ACL reconstruction. The early proteomic PTOA response is more similar to inflammatory rheumatoid arthritis than idiopathic OA; thus, long-acting agents which better regulate pro-inflammatory cytokine activity may more successfully limit tissue destruction. By re-purposing approved therapeutics with proven immune efficacy, a readily-available and cost-effective strategy for disease modification may be possible.
Montelukast was first approved for clinical use in 1998 for prophylaxis and chronic treatment of asthma. The drug selectively inhibits the cysteinyl leukotriene receptor 1 (CysLT1). Montelukast blocks the actions of cysteinyl leukotriene D4 (LTD4), which is produced through the arachidonic acid pathway. This pro-inflammatory signal is released from several cells including the inflammatory mast cells and eosinophils. Montelukast also appears to address multiple PTOA mechanisms by inhibiting cysteinyl leukotrienes. Cysteinyl leukotriene inhibition in animal and laboratory models of PTOA resulted in the elimination of senescent cells, reduced NFkB activation, decreased concentrations of pro-inflammatory and catabolic factors and reactive oxygen species (ROS) while increasing expression of anti-inflammatory factors (inducing anti-inflammatory M2 macrophage infiltration), inhibiting osteoclastogenesis and improving bone quality. The novel use of oral montelukast offers the potential of a disease modifying treatment to prevent irreversible cartilage loss after ACL injury.
- Conditions
- ACL Injury, Meniscus Tear, Post-traumatic Osteoarthritis
- Being tested
- Montelukast, Placebo
- Keywords
- knee ligament, osteoarthritis
- Medical subject headings
- Anterior Cruciate Ligament Injuries, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MontelukastDrug
Also called Singulair
The novel use of oral montelukast offers the potential of a disease modifying treatment to prevent irreversible cartilage loss after ACL injury. 10mg of oral Montelukast will be taken daily for 6 months post surgery.
PlaceboDrug
An oral placebo will be taken daily for 6 months post surgery.
| Study group | Role | What they receive |
|---|---|---|
| Montelukast | Experimental | Patients will receive oral montelukast (10 mg) daily for 6 months after surgery. Receives: Drug: Montelukast |
| Placebo | Placebo comparator | Patients will receive an oral placebo daily for 6 months after surgery. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum prostaglandin E2
Prostaglandin E2 is a potential inflammatory mediator, and it is being measured to directly assess whether treatment reduces this systemic inflammatory marker. Greater serum prostaglandin is associated with greater inflammation.
Measured: Change between Visit 3 (10 days post surgery) and Visit 6 (1 year post surgery)
T1rho relaxation time on MRI
T1rho relaxation time is a validated measure of proteoglycan content within the cartilage, and can be assessed on MRI. Increased T1rho relaxation time is associated with increased cartilage degeneration.
Measured: Change between Visit 4 (4 weeks post surgery) and Visit 6 (1 year post surgery)
Shape of the medial femoral condyle on MRI
The shape of the medial femoral condyle has been previously demonstrated to change after ACL reconstruction and is predictive of later cartilage changes. Flattening and widening of the medial femoral condyle are considered to be indicative of later cartilage changes.
Measured: Change between Visit 4 (4 weeks post surgery) and Visit 6 (1 year post surgery)
Knee injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome instrument that is comprised of 5 subscales (Pain, Symptoms, Activities of Daily Living, Sports and Recreation, and Quality of Life) with each scale being scored from 0 to 100 with higher scores being indicative of a superior outcome.
Measured: Change between Visit 3 (10 days post surgery) and Visit 6 (1 year post surgery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2020
- Study start1 Feb 2021
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ACL InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Austin V Stone
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Austin V Stone, University of Kentucky
- Investigators
- Austin Stone, MD, PhD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04572256
- Sponsor's protocol ID
- 60266
- Acronym
- MOCHA
- Status last verified
- Jun 2026
- First submitted
- 25 Sep 2020
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jacobs CA, Conley CEW, Kraus VB, Lansdown DA, Lau BC, Li X, Majumdar S, Spindler KP, Lemaster NG, Stone AV. MOntelukast as a potential CHondroprotective treatment following Anterior cruciate ligament reconstruction (MOCHA Trial): study protocol for a double-blind, randomized, placebo-controlled clinical trial. Trials. 2022 Jan 31;23(1):98. doi: 10.1186/s13063-021-05982-3.
PubMed 35101085
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MOntelukast as a Potential CHondroprotective Treatment Following Anterior Cruciate Ligament Reconstruction (MOCHA Trial)
- ClinicalTrials.gov ID
- NCT04572256
- Acronym / sponsor ID
- MOCHA / 60266
- Conditions
- ACL Injury, Meniscus Tear, Post-traumatic Osteoarthritis
- Keywords
- knee ligament, osteoarthritis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Austin V StoneUniversity, hospital or other
- Collaborators
- Duke University, The Cleveland Clinic, University of California, San Francisco
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 1 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
After anterior cruciate ligament (ACL) reconstruction, patient-reported outcomes are improved 10 years post-surgery. Cytokine concentrations, however, remain elevated years after surgery; over 80% of patients with combined ACL and meniscus injuries have post-traumatic osteoarthritis (PTOA) within 10-15 years after injury. Since pain nociceptors are not located in the articular cartilage, patient-reported outcomes improve despite progressive, irreversible cartilage loss, thus making PTOA a "silent killer." Because early cartilage loss progresses without pain and dysfunction, the prevalence of PTOA continues to increase. PTOA now represents the most common cause of military disability.
Our recent results illustrate the downstream cytokine and degradative enzyme activity following ACL reconstruction. ACL and meniscus injury initiate a biochemical cascade resulting in cartilage degradation and this process involves an up-regulated pro-inflammatory response with a dysregulated anti-inflammatory response. Single-dose intra-articular anti-inflammatory treatment appears to reduce hyaline cartilage degradation shortly after the time of injury based on synovial fluid measures of type II collagen degradation. The intra-articular inflammatory milieu at the time of surgery appears to predict the patient symptom state two years later; however, the effectiveness of preoperative anti-inflammatory treatments in impacting patient symptoms or slowing long-term PTOA progression is as yet unclear. A lack of efficacy in preoperative interventions may be attributed to a profound inflammatory stimulus from surgical reconstruction of the ACL. The postoperative inflammatory cascade results in articular cartilage and meniscus degradation due to matrix degrading enzymes, especially those which breakdown type II collagen.
PTOA affects the whole joint organ including the cartilage, synovium, and bone. PTOA progression is multifaceted and includes activation of the pro-inflammatory Nuclear Factor Kappa-B (NFkB) pathway, an increase in pro-inflammatory M1 macrophages, cell senescence, and bone remodeling. Limiting the biochemical cascade through an innovative disease modifying treatment to target upstream activity will potentially treat all components of the knee, thereby lessening the inflammatory response, reducing cartilage catabolism, and potentially improving pathologic bony remodeling observed after ACL reconstruction. The early proteomic PTOA response is more similar to inflammatory rheumatoid arthritis than idiopathic OA; thus, long-acting agents which better regulate pro-inflammatory cytokine activity may more successfully limit tissue destruction. By re-purposing approved therapeutics with proven immune efficacy, a readily-available and cost-effective strategy for disease modification may be possible.
Montelukast was first approved for clinical use in 1998 for prophylaxis and chronic treatment of asthma. The drug selectively inhibits the cysteinyl leukotriene receptor 1 (CysLT1). Montelukast blocks the actions of cysteinyl leukotriene D4 (LTD4), which is produced through the arachidonic acid pathway. This pro-inflammatory signal is released from several cells including the inflammatory mast cells and eosinophils. Montelukast also appears to address multiple PTOA mechanisms by inhibiting cysteinyl leukotrienes. Cysteinyl leukotriene inhibition in animal and laboratory models of PTOA resulted in the elimination of senescent cells, reduced NFkB activation, decreased concentrations of pro-inflammatory and catabolic factors and reactive oxygen species (ROS) while increasing expression of anti-inflammatory factors (inducing anti-inflammatory M2 macrophage infiltration), inhibiting osteoclastogenesis and improving bone quality. The novel use of oral montelukast offers the potential of a disease modifying treatment to prevent irreversible cartilage loss after ACL injury.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Montelukast | Experimental | Drug: MontelukastPatients will receive oral montelukast (10 mg) daily for 6 months after surgery. |
| Placebo | Placebo comparator | Drug: PlaceboPatients will receive an oral placebo daily for 6 months after surgery. |
Who may qualify
- Ages
- 25 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Undergoing primary ACL reconstruction
- Age between 25-50
- Concomitant meniscus injury
Key exclusion criteria (4 listed)
- Undergoing revision procedures
- Multiple ligament injuries requiring multiple ligament reconstruction/repair
- Depressive symptoms and/or those who endorse suicidal ideation at the time of enrollment (PHQ-9 score >= 15)
- Found to not have a meniscus tear at the time of surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MontelukastAlso: SingulairThe novel use of oral montelukast offers the potential of a disease modifying treatment to prevent irreversible cartilage loss after ACL injury. 10mg of oral Montelukast will be taken daily for 6 months post surgery. | Drug | Montelukast |
| PlaceboAn oral placebo will be taken daily for 6 months post surgery. | Drug | Placebo |
Primary outcome
Serum prostaglandin E2
Time frame: Change between Visit 3 (10 days post surgery) and Visit 6 (1 year post surgery)
Prostaglandin E2 is a potential inflammatory mediator, and it is being measured to directly assess whether treatment reduces this systemic inflammatory marker. Greater serum prostaglandin is associated with greater inflammation.
T1rho relaxation time on MRI
Time frame: Change between Visit 4 (4 weeks post surgery) and Visit 6 (1 year post surgery)
T1rho relaxation time is a validated measure of proteoglycan content within the cartilage, and can be assessed on MRI. Increased T1rho relaxation time is associated with increased cartilage degeneration.
Shape of the medial femoral condyle on MRI
Time frame: Change between Visit 4 (4 weeks post surgery) and Visit 6 (1 year post surgery)
The shape of the medial femoral condyle has been previously demonstrated to change after ACL reconstruction and is predictive of later cartilage changes. Flattening and widening of the medial femoral condyle are considered to be indicative of later cartilage changes.
Knee injury and Osteoarthritis Outcome Score (KOOS)
Time frame: Change between Visit 3 (10 days post surgery) and Visit 6 (1 year post surgery)
The KOOS is a patient-reported outcome instrument that is comprised of 5 subscales (Pain, Symptoms, Activities of Daily Living, Sports and Recreation, and Quality of Life) with each scale being scored from 0 to 100 with higher scores being indicative of a superior outcome.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- Derived from this study: PubMed 35101085Jacobs CA, Conley CEW, Kraus VB, Lansdown DA, Lau BC, Li X, Majumdar S, Spindler KP, Lemaster NG, Stone AV. MOntelukast as a potential CHondroprotective treatment following Anterior cruciate ligament reconstruction (MOCHA Trial): study protocol for a double-blind, randomized, placebo-controlled clinical trial. Trials. 2022 Jan 31;23(1):98. doi: 10.1186/s13063-021-05982-3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Austin Stone, MD, PhD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Montelukast in people with ACL Injury and Meniscus Tear, run by Austin V Stone at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Austin Stone, MD, PhD (859.218.3065, austin.stone@uky.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum prostaglandin E2 (time frame: Change between Visit 3 (10 days post surgery) and Visit 6 (1 year post surgery)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04572256, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2026.