ACL Injury, ACL Reconstruction, Scar Formation
Conditions
Keywords
ACL, Postoperative Arthrofibrosis, Losartan
Brief summary
The purpose of this study to investigate the effect of using losartan (a blood pressure lowering drug with anti-scarring properties) on preventing primary postoperative arthrofibrosis (formation of abnormal scar tissue) in the knees in participants undergoing anterior cruciate ligament (ACL) repair surgery of their knee.
Detailed description
Losartan, an angiotensin-II receptor blocker (ARB), approved by the Food and Drug Administration (FDA) for the treatment of hypertension and diabetic nephropathy, has garnered recent interest in the field of orthopedic surgery as an anti-fibrotic (anti-scarring) agent. Losartan's primary mechanism of action as an anti-hypertensive involves acting as a receptor antagonist for angiotensin II, a peptide produced by the liver which causes vasoconstriction, release of anti-diuretic hormone from the pituitary gland, and release of aldosterone from the adrenal glands, among other functions. Losartan secondary function is to act as a TGF-β1 blocker. TGF-β1 has been implicated in pro-fibrotic pathways in multiple organs systems. Losartan, initially as a treatment for hypertension and diabetic nephropathy, was found to have benefits against fibrosis in the renal system. As a result, the use of losartan has gained interest in several other fields in medicine, including plastic surgery for wound healing and keloid prevention, in ophthalmology to prevent corneal scarring, and orthopedic surgery. The potential use of losartan presents an attractive anti-fibrotic prophylaxis candidate against the formation of postoperative arthrofibrosis following ACLR.
Interventions
DRUGLosartan
Two types of losartan capsules will be compounded by combining a broken-up 25mg or 50mg losartan tablet and microcrystalline cellulose placebo filler to eliminate rattling of the broken tablet inside of the capsule. The 25mg losartan capsules will be yellow and the 50 mg losartan capsules will be blue.
OTHERPlacebo
The placebo capsules will consist of microcrystal cellulose and will come in yellow and blue to appear identical to the losartan capsules.
Sponsors
Arthroscopy Association of North America (AANA)
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be undergoing a primary ACLR with or without the following: * Chondroplasty * Synovectomy * Loose body removal * Removal of hardware * Meniscal surgery (excluding meniscal allograft transplantation/MAT) * Lateral extra-articular tenodesis * Must have skeletal maturity in the distal femur and proximal tibial physes * Must be age 18 years or older at time of enrollment
Exclusion criteria
* \<18 years at time of enrollment * No diagnosis of ACL tear * ACL repairs * Revision ACL reconstructions * Open distal femur or proximal tibia physes * Major concomitant procedures (such as osteotomy, MAT, or cartilage restoration surgery) * History of prior proximal or distal femur fracture (including those receiving nonoperative treatment) * History of prior ipsilateral femur or tibia osteomyelitis * Medical history * History of hypotensive disease, including postural orthostatic hypotension syndrome (POTS), autonomic dysreflexia, or Shy-Drager syndrome (aka multiple system atrophy), baseline hypotension \<90 systolic or \<60 diastolic mmHg. * History of significant hepatic disease (liver transplantation, cirrhosis of any cause, or any liver disease with Child-Pugh classification B or C) due to hepatic metabolism of ARBs. * Chronic kidney disease * Rheumatologic disorders on immunologic medications * Current medications including diuretics (i.e. furosemide), lithium, and spironolactone * Current hypertension with prescription of an ARB or ACE-I * Allergy to losartan * Current pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Range of Motion | 12 months | Range of motion measured from baseline to 12 months |
Countries
United States
Contacts
Primary ContactJorge Chahla, MD, PhD
Backup ContactAndrew Bi, MD
Outcome results
None listed