Overcoming TWEAK Signaling to Restore Muscle and Mobility After Joint Replacement

NCT02628795 | Completed DMC

• 1 other identifier: R01HD084124
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This single-blind, randomized, controlled trial is designed to test the effect of an intensive, 16 week exercise rehabilitation program (progressive resistance training + functional mobility training) vs. usual care on restoration of muscle mass and mobility after total hip (THA) or knee (TKA) arthroplasty in men and women with end-stage osteoarthritis. The molecular basis underlying the trial is the presence of significant muscle inflammation susceptibility in many of these individuals, and the expectation that the more intensive intervention will overcome this inflammatory burden to facilitate recovery.

Conditions

Osteoarthritis

Keywords

total hip arthroplasty; total knee arthroplasty

Outcome Measures

Primary Outcomes (4)

• Change in unilateral (surgical) thigh muscle mass (unit of measure = grams)

  Primary muscle mass outcome of Aim 1

  Pre-surgery to 16 weeks post-surgery

• Change in unilateral (surgical) knee extension power (unit of measure = watts)

  Primary functional outcome of Aim 1

  Pre-surgery to 16 weeks post-surgery

• Change in short physical performance battery (SPPB) (unit of measure = score)

  Primary outcome of Aim 3

  From 16 weeks post-surgery to 26 and 52 weeks post-surgery

• Muscle inflammation susceptibility (MuIS) status (unit of measure = relative value)

  Primary outcome of Aim 2: Muscle inflammation susceptibility (MuIS) defined by TWEAK receptor gene expression

  At the time of surgery

Secondary Outcomes (3)

• Change in muscle fiber size (unit of measure = micrometers squared)

  From the time of surgery to 16 weeks post-surgery

• Change in unilateral (surgical) knee extension isometric strength (unit of measure = Newton-meters)

  Pre-surgery to 16 weeks post-surgery

• Change in maximum 10-meter gait speed (unit of measure = meters per second)

  Pre-surgery to 16 weeks post-surgery

Other Outcomes (7)

• Change in free-living physical activity (unit of measure = steps per day)

  Pre-surgery to 8, 16, 26, and 52 weeks post-surgery

• Change in self-reported health status (unit of measure = score)

  Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery

• Change in cellular and molecular markers (unit of measure = arbitrary units)

  From the time of surgery to 16 weeks post-surgery

Study Arms (2)

PRT + FM

EXPERIMENTAL

Progressive resistance training + functional mobility training 3 d/wk x 16 wk

Behavioral: PRT + FM; Other: Usual Care

Usual Care

ACTIVE COMPARATOR

Post-surgical usual care including physical therapy

Other: Usual Care

Interventions

PRT + FM BEHAVIORAL

Supervised progressive resistance training + functional mobility training (PRT+FM) 3 days per week for 16 weeks post-surgery.

PRT + FM

Usual Care OTHER

Post-surgical usual care activities including any prescribed physical therapy

PRT + FM; Usual Care

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages 40 and 80 y.
• Scheduled to undergo elective total hip or knee replacement specifically for the surgical indication of end-stage osteoarthritis.
• First-time hip or knee replacement.
• Capable of providing informed consent (cognitively intact if consenting to surgery).

You may not qualify if:

• Any surgical indication other than first-time total joint replacement specifically for end-stage osteoarthritis.
• Bilateral knee/ hip replacement
• History of alcoholism or liver disease.
• Any history of hypo- or hyper-coagulation disorders including subjects taking Coumadin.
• Any individual with end-stage disease and/or a life expectancy less than one year.
• Pregnancy.
• Lactating Women.
• Neurological, musculoskeletal, or other disorder that would preclude them from completing the exercise training intervention and all performance tests.
• Uncontrolled hypertension, unstable or exercise-induced angina pectoris or myocardial ischemia, congestive heart failure.
• Uncontrolled diabetes mellitus.
• Lidocaine allergy (1% lidocaine is the local anesthetic used during the muscle biopsy procedure).
• Phenylketonuria (phenylalanine tracer for metabolic studies).
• Currently receiving androgen (e.g., testosterone) or anabolic (e.g., growth hormone (GH), insulin-like growth factor-I (IGF-I)) therapy.
• Body mass index ≥ 35.
• History of lower body progressive resistance training within the past year.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

UAB Center for Exercise Medicine

Birmingham, Alabama, 35205, United States

Location

MeSH Terms

Conditions

Osteoarthritis

Interventions

Hypoxanthine Phosphoribosyltransferase

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Pentosyltransferases; Glycosyltransferases; Transferases; Enzymes; Enzymes and Coenzymes

Study Officials

• Marcas M Bamman, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• S Louis Bridges, MD, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, UAB Center for Exercise Medicine

Study Record Dates

• First Submitted: August 5, 2015
• First Posted: December 11, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2020
• Study Completion: February 28, 2021
• Last Updated: July 7, 2021

Record last verified: 2021-07

Locations

US (1)