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Losartan to Improve Hip Microfracture

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ClinicalTrials.gov Identifier: NCT04212650
Recruitment Status : Terminated (redesigned trial using another placebo controlled drug)
First Posted : December 27, 2019
Last Update Posted : December 17, 2020
Sponsor:
Collaborators:
United States Department of Defense
Office of Naval Research (ONR)
Information provided by (Responsible Party):
Steadman Philippon Research Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Hip Osteoarthritis Hip Impingement Syndrome Cartilage Damage Fibrosis Drug: Losartan Other: Placebo Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Block Randomization
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Biologically Regulated Marrow Stimulation by Blocking Fibrosis to Improve Cartilage Repair: A Randomized Double-Blind, Placebo-Controlled Study
Actual Study Start Date : January 16, 2020
Actual Primary Completion Date : December 4, 2020
Actual Study Completion Date : December 4, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Potassium

Arm Intervention/treatment
Experimental: Losartan
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.
Drug: Losartan
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.
Other Name: Losartan Potassium

Placebo Comparator: Placebo
Appearance-matched placebo capsules, oral administration, twice daily, taken for 30 consecutive days starting on the evening of the second post-surgery day.
Other: Placebo
Appearance-matched microcrystalline cellulose placebo




Primary Outcome Measures :
  1. 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 adverse events


Secondary Outcome Measures :
  1. Patient Reported Outcomes Questionnaire [ Time Frame: Baseline, 3 months, 6 months, 12 months and 18 months ]

    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.

  2. Patient Reported Outcomes Questionnaire [ Time Frame: Baseline, 3 months, 6 months, 12 months and 18 months ]

    Patient Satisfaction

    • Scale from 1-10.
    • Higher score represents greater patient satisfaction.

  3. Patient Reported Outcomes Questionnaire [ Time Frame: Baseline, 3 months, 6 months, 12 months and 18 months ]

    Harris Hip Score (HHS).

    • Scale from 0-100.
    • Higher score represents greater hip health.

  4. Patient Reported Outcomes Questionnaire [ Time Frame: Baseline, 3 months, 6 months, 12 months and 18 months ]

    Hip Outcome Score (HOS) - Including Sport and Activities of Daily Living (ADL) subscales.

    • Scale from 0-100.
    • Higher score represents greater hip health.

  5. Patient Reported Outcomes Questionnaire [ Time Frame: Baseline, 3 months, 6 months, 12 months and 18 months ]

    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.

  6. Patient Reported Outcomes Questionnaire [ Time Frame: Baseline, 3 months, 6 months, 12 months and 18 months ]

    Tegner Activity Scale

    • Scale from 0-10.
    • Higher score represents greater activity level.

  7. Patient Reported Outcomes Questionnaire [ Time Frame: Baseline, 3 months, 6 months, 12 months and 18 months ]

    Numeric Rating Scale (NRS) for Pain

    • Scale from 1-10.
    • Higher score represents greater pain.

  8. Morphological and Quantitative Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline and 12 months ]
    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.

  9. Physical Examination of the Hip [ Time Frame: Baseline, 3 months, and 12 months ]
    Standard physical exam assessment of hip strength, measured in Newtons.

  10. Physical Examination of the Hip [ Time Frame: Baseline, 3 months, and 12 months ]
    Standard physical exam assessments of hip range of motion (ROM), measured in degrees.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04212650


Locations
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United States, Colorado
Steadman Philippon Research Institute
Vail, Colorado, United States, 81657
Sponsors and Collaborators
Steadman Philippon Research Institute
United States Department of Defense
Office of Naval Research (ONR)
Investigators
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Principal Investigator: Marc J Philippon, MD Steadman Philippon Research Institute
  Study Documents (Full-Text)

Documents provided by Steadman Philippon Research Institute:
Informed Consent Form  [PDF] May 13, 2020

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Responsible Party: Steadman Philippon Research Institute
ClinicalTrials.gov Identifier: NCT04212650    
Other Study ID Numbers: 2019-15
First Posted: December 27, 2019    Key Record Dates
Last Update Posted: December 17, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Steadman Philippon Research Institute:
Cartilage Microfracture
Losartan
Transforming growth factor beta 1
Hip Arthroscopy
Additional relevant MeSH terms:
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Osteoarthritis, Hip
Fibrosis
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Pathologic Processes
Losartan
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action