Losartan to Improve Hip Microfracture

Hip Osteoarthritis Clinical Trial

Official title:

Biologically Regulated Marrow Stimulation by Blocking Fibrosis to Improve Cartilage Repair: A Randomized Double-Blind, Placebo-Controlled Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04212650
• Other study ID #: 2019-15
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 7, 2020
• Est. completion date: December 4, 2020

Study information

• Verified date: October 2023
• Source: Steadman Philippon Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 4, 2020
• Est. primary completion date: December 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Cartilage Damage
• Fibrosis
• Hip Impingement Syndrome
• Hip Osteoarthritis
• Osteoarthritis, Hip

Intervention

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:
• Placebo
Appearance-matched microcrystalline cellulose placebo

Locations

Country	Name	City	State
United States	Steadman Philippon Research Institute	Vail	Colorado

Sponsors (3)

Lead Sponsor	Collaborator
Steadman Philippon Research Institute	Office of Naval Research (ONR), United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events	Occurrence of treatment-emergent adverse events	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	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.	Baseline, 3 months, 6 months, 12 months and 18 months
Secondary	Patient Reported Outcomes Questionnaire - Patient Satisfaction	Patient Satisfaction; Scale from 1-10.; Higher score represents greater patient satisfaction.	Baseline, 3 months, 6 months, 12 months and 18 months
Secondary	Patient Reported Outcomes Questionnaire - Harris Hip Score	Harris Hip Score (HHS).; Scale from 0-100.; Higher score represents greater hip health.	Baseline, 3 months, 6 months, 12 months and 18 months
Secondary	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.	Baseline, 3 months, 6 months, 12 months and 18 months
Secondary	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.	Baseline, 3 months, 6 months, 12 months and 18 months
Secondary	Patient Reported Outcomes Questionnaire - Tegner Activity Scale	Tegner Activity Scale; Scale from 0-10.; Higher score represents greater activity level.	Baseline, 3 months, 6 months, 12 months and 18 months
Secondary	Patient Reported Outcomes Questionnaire - Numeric Rating Scale for Pain	Numeric Rating Scale (NRS) for Pain; Scale from 1-10.; Higher score represents greater pain.	Baseline, 3 months, 6 months, 12 months and 18 months
Secondary	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.	Baseline and 12 months
Secondary	Physical Examination of the Hip - Strength	Standard physical exam assessment of hip strength, measured in Newtons.	Baseline, 3 months, and 12 months
Secondary	Physical Examination of the Hip - Range of Motion	Standard physical exam assessments of hip range of motion (ROM), measured in degrees.	Baseline, 3 months, and 12 months