Hip OsteoarthritisPhase 1/2NCT04212650
Losartan to Improve Hip Microfracture
A Phase 1/2 study testing Losartan in people with Hip Osteoarthritis and Hip Impingement Syndrome, run by Steadman Philippon Research Institute at 1 site in United States.
Trial summary
Phase I/IIA randomized, double-blind, placebo-controlled clinical trial to assess safety and efficacy of oral losartan for improving cartilage repair following microfracture to treat focal cartilage defects during hip arthroscopy. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Hip Osteoarthritis, Hip Impingement Syndrome, Cartilage Damage
- What is being tested?
- Losartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Aug 2020to 4 Dec 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Underwent primary hip arthroscopy
- Underwent baseline quantitative MRI at The Steadman Clinic (TSC)
- Single, localized, grade 3 or 4 cartilage lesion of the acetabulum or femoral head treated with Bone Marrow Stimulation (BMS; i.e. microfracture)
- Aged 18-60 at time of surgery
- Tonnis grade 1 or less
Who cannot join
- Two or more cartilage lesions of grade 3 or 4
- Less than 2 mm of minimal hip joint space
- Osteoarthritis or diffuse change of cartilage
- Non-English speaking
- Prior hip surgery on operative hip
- Pre-existing bony deformity caused by previous fracture(s)
Show all 14Show fewer
- Synovial chondromatosis
- Pigmented Villonodular Synovitis (PVNS)
- Dysplasia (center edge angle <20 degrees)
- History of Avascular Necrosis (AVN), Perthes disease, or slipped capital femoral epiphysis (SCFE)
- Inflammatory arthritis or other arthritis caused by autoimmune disease
- Patients allergic to any active or inactive ingredient of losartan
- Patients taking medication with known losartan interaction, including phenobarbital, rifampin, and fluconazole.
- Subjects that are currently taking losartan
Trial locations and contacts
1 site in 1 country.
United States1 site
Steadman Philippon Research Institute
Vail, Colorado, 81657
About this study
Official title: Biologically Regulated Marrow Stimulation by Blocking Fibrosis to Improve Cartilage Repair: A Randomized Double-Blind, Placebo-Controlled Study
Phase I/IIA randomized, double-blind, placebo-controlled clinical trial to assess safety and efficacy of oral losartan for improving cartilage repair following microfracture to treat focal cartilage defects during hip arthroscopy.
Read the detailed description
This is a prospective, double-blind, placebo-controlled, randomized clinical trial that will be conducted at The Steadman Clinic and Steadman Philippon Research Institute.
Articular cartilage defects that extend full thickness to subchondral bone rarely heal without intervention. Some patients may not develop clinically significant problems from acute full-thickness chondral defects, but many eventually suffer from debilitating degenerative changes. Microfracture is the most commonly used first-line treatment technique for chondral lesions in the hip, however, this procedure's effectiveness is limited by the repair tissue being a hybrid of hyaline and fibrocartilage. We hypothesize that administration of a transforming growth factor beta 1 (TGF-β1) blocker, losartan (an approved hypertension drug, angiotensin II receptor antagonist) with microfracture will enhance articular cartilage repair as assessed on quantitative magnetic resonance imaging. We will also measure patient benefit through the recording of patient reported outcomes in the 18 months following surgery. The Division of Pulmonary, Allergy and Rheumatology Products within the Center for Drug Evaluation and Research at the Food and Drug Administration has granted an investigational new drug (IND) exemption to pursue this trial in accordance with 21 CFR 312.2(b).
- Being tested
- Losartan, Placebo
- Keywords
- Cartilage Microfracture, Losartan, Transforming growth factor beta 1, Hip Arthroscopy
- Medical subject headings
- Osteoarthritis, Hip, Fibrosis, Camurati-Engelmann Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Losartan Potassium
Losartan will be administered to improve the quality of hip cartilage repair following arthroscopic microfracture. Losartan is a known anti-fibrotic agent via blocking of TGF-B1.
PlaceboOther
Appearance-matched microcrystalline cellulose placebo
| Study group | Role | What they receive |
|---|---|---|
| Losartan | Experimental | 12.5mg Losartan capsules, oral administration, twice daily (25mg total per day), taken for 30 consecutive days starting on the evening of the second post-surgery day. Receives: Drug: Losartan |
| Placebo | Placebo comparator | Appearance-matched placebo capsules, oral administration, twice daily, taken for 30 consecutive days starting on the evening of the second post-surgery day. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Occurrence of treatment-emergent adverse events
Measured: Drug related adverse events will be monitored during the medication phase (post-op days 2-31) and orthopaedic-related health and function will be monitored for the entire study duration (18 months).
Secondary outcomes (10)
Patient Reported Outcomes Questionnaire
12-question Short-Form General Health Survey (SF-12) - Including Physical Component Summary (PCS) and Mental Component Summary (MCS).
- Higher score represents greater health.
- Scale standardized to a US Population mean of 50 and standard deviation of 10 points.
Measured: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Patient Satisfaction
Patient Satisfaction
- Scale from 1-10.
- Higher score represents greater patient satisfaction.
Measured: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Harris Hip Score
Harris Hip Score (HHS).
- Scale from 0-100.
- Higher score represents greater hip health.
Measured: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Hip Outcome Score
Hip Outcome Score (HOS) - Including Sport and Activities of Daily Living (ADL) subscales.
- Scale from 0-100.
- Higher score represents greater hip health.
Measured: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Western Ontario and McMaster Universities Osteoarthritis Index
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) - Including Pain, Stiffness and Physical Function subscales.
- Scale from 0-96.
- Higher score represents worse hip health.
Measured: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Tegner Activity Scale
Tegner Activity Scale
- Scale from 0-10.
- Higher score represents greater activity level.
Measured: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Numeric Rating Scale for Pain
Numeric Rating Scale (NRS) for Pain
- Scale from 1-10.
- Higher score represents greater pain.
Measured: Baseline, 3 months, 6 months, 12 months and 18 months
Morphological and Quantitative Magnetic Resonance Imaging (MRI)
Cartilage quality assessed by blinded radiologist using morphological MRI. Quantitative MRI using T2 mapping images with texture analysis used to assess water content and collagen organization within the cartilage and surrounding tissue.
Measured: Baseline and 12 months
Physical Examination of the Hip - Strength
Standard physical exam assessment of hip strength, measured in Newtons.
Measured: Baseline, 3 months, and 12 months
Physical Examination of the Hip - Range of Motion
Standard physical exam assessments of hip range of motion (ROM), measured in degrees.
Measured: Baseline, 3 months, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2019
- Study start7 Aug 2020
- Primary completion4 Dec 2020
- Study completion4 Dec 2020
Why it stopped: redesigned trial using another placebo controlled drug
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hip OsteoarthritisStudies 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
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Block Randomization
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steadman Philippon Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, Office of Naval Research (ONR)
- Responsible party
- Sponsor
- Investigators
- Marc J Philippon, MD, Principal investigator, Steadman Philippon Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04212650
- Sponsor's protocol ID
- 2019-15
- Status last verified
- Oct 2023
- First submitted
- 19 Dec 2019
- Last updated
- 30 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biologically Regulated Marrow Stimulation by Blocking Fibrosis to Improve Cartilage Repair: A Randomized Double-Blind, Placebo-Controlled Study
- ClinicalTrials.gov ID
- NCT04212650
- Acronym / sponsor ID
- 2019-15
- Keywords
- Cartilage Microfracture, Losartan, Transforming growth factor beta 1, Hip Arthroscopy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: redesigned trial using another placebo controlled drug
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Steadman Philippon Research InstituteUniversity, hospital or other
- Collaborators
- United States Department of Defense, Office of Naval Research (ONR)
- Study start
- 7 Aug 2020 (actual)
- Primary completion
- 4 Dec 2020 (actual)
- Study completion
- 4 Dec 2020 (actual)
- First posted
- 27 Dec 2019 (actual)
- Results
- Posted 30 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase I/IIA randomized, double-blind, placebo-controlled clinical trial to assess safety and efficacy of oral losartan for improving cartilage repair following microfracture to treat focal cartilage defects during hip arthroscopy.
Detailed description
This is a prospective, double-blind, placebo-controlled, randomized clinical trial that will be conducted at The Steadman Clinic and Steadman Philippon Research Institute.
Articular cartilage defects that extend full thickness to subchondral bone rarely heal without intervention. Some patients may not develop clinically significant problems from acute full-thickness chondral defects, but many eventually suffer from debilitating degenerative changes. Microfracture is the most commonly used first-line treatment technique for chondral lesions in the hip, however, this procedure's effectiveness is limited by the repair tissue being a hybrid of hyaline and fibrocartilage. We hypothesize that administration of a transforming growth factor beta 1 (TGF-β1) blocker, losartan (an approved hypertension drug, angiotensin II receptor antagonist) with microfracture will enhance articular cartilage repair as assessed on quantitative magnetic resonance imaging. We will also measure patient benefit through the recording of patient reported outcomes in the 18 months following surgery. The Division of Pulmonary, Allergy and Rheumatology Products within the Center for Drug Evaluation and Research at the Food and Drug Administration has granted an investigational new drug (IND) exemption to pursue this trial in accordance with 21 CFR 312.2(b).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Block Randomization
| Arm | Type | Receives |
|---|---|---|
| Losartan | Experimental | Drug: Losartan12.5mg Losartan capsules, oral administration, twice daily (25mg total per day), taken for 30 consecutive days starting on the evening of the second post-surgery day. |
| Placebo | Placebo comparator | Other: PlaceboAppearance-matched placebo capsules, oral administration, twice daily, taken for 30 consecutive days starting on the evening of the second post-surgery day. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Underwent primary hip arthroscopy
- Underwent baseline quantitative MRI at The Steadman Clinic (TSC)
- Single, localized, grade 3 or 4 cartilage lesion of the acetabulum or femoral head treated with Bone Marrow Stimulation (BMS; i.e. microfracture)
- Aged 18-60 at time of surgery
- Tonnis grade 1 or less
Key exclusion criteria (14 listed)
- Two or more cartilage lesions of grade 3 or 4
- Less than 2 mm of minimal hip joint space
- Osteoarthritis or diffuse change of cartilage
- Non-English speaking
- Prior hip surgery on operative hip
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 |
|---|---|---|
| LosartanAlso: Losartan PotassiumLosartan will be administered to improve the quality of hip cartilage repair following arthroscopic microfracture. Losartan is a known anti-fibrotic agent via blocking of TGF-B1. | Drug | Losartan |
| PlaceboAppearance-matched microcrystalline cellulose placebo | Other | Placebo |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: Drug related adverse events will be monitored during the medication phase (post-op days 2-31) and orthopaedic-related health and function will be monitored for the entire study duration (18 months).
Occurrence of treatment-emergent adverse events
10 secondary outcomes
Patient Reported Outcomes Questionnaire
Time frame: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Patient Satisfaction
Time frame: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Harris Hip Score
Time frame: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Hip Outcome Score
Time frame: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Western Ontario and McMaster Universities Osteoarthritis Index
Time frame: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Tegner Activity Scale
Time frame: Baseline, 3 months, 6 months, 12 months and 18 months
Patient Reported Outcomes Questionnaire - Numeric Rating Scale for Pain
Time frame: Baseline, 3 months, 6 months, 12 months and 18 months
Morphological and Quantitative Magnetic Resonance Imaging (MRI)
Time frame: Baseline and 12 months
Physical Examination of the Hip - Strength
Time frame: Baseline, 3 months, and 12 months
Physical Examination of the Hip - Range of Motion
Time frame: Baseline, 3 months, and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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. This study is not recruiting at the moment.
Marc J Philippon, MD principal investigator
Steadman Philippon Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Losartan in people with Hip Osteoarthritis and Hip Impingement Syndrome, run by Steadman Philippon Research Institute 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 5 inclusion and 14 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: stopped early, as of the sponsor's last update on 30 Oct 2023. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: Drug related adverse events will be monitored during the medication phase (post-op days 2-31) and orthopaedic-related health and function will be monitored for the entire study duration (18 months).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Oct 2023.