- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT02628795
Overcoming TWEAK Signaling to Restore Muscle and Mobility After Joint Replacement (TWEAK)
3. Juli 2021 aktualisiert von: Marcas M. Bamman, PhD, University of Alabama at Birmingham
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.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
While elective total hip (THA) and knee (TKA) arthroplasty relieve pain and improve mobility function for thousands with end-stage osteoarthritis (OA), up to 35% endure persistent muscle atrophy and mobility limitations for several years that impact life quality, increase morbidity, and burden the healthcare system.
Given that THA/TKA volumes are increasing exponentially with >1.1 million in the US annually, refractory mobility impairment is a major public health problem.
Together, the available data raise two important knowledge gaps in THA/TKA rehabilitation: (i) poorly understood factors that limit responsiveness of a large number of patients to current usual care; and (ii) the absence of rehabilitation programs proven to overcome these limitations.
The proposed project is designed to fill these gaps.
The investigators' fundamental tenet is that restoration of mobility function following THA/TKA requires: (i) regeneration of surgically damaged muscle; and (ii) regrowth of muscles that have atrophied over years of OA and limited usage.
The investigators suggest a major cause of muscle regeneration impairment in some individuals is what the investigators identified as muscle inflammation susceptibility (MuIS) - hyperactive inflammatory signaling in muscle of MuIS(+) individuals despite no systemic inflammation - which also manifests in isolated primary satellite cells and inhibits myogenesis in vitro, indicative of a true cellular phenotype beyond the niche.
The investigators' preliminary findings in THA/TKA patients strongly suggest the tumor necrosis factor-like weak inducer of apoptosis (TWEAK) signaling pathway may be central to MuIS and impaired THA/TKA recovery, as high perioperative muscle TWEAK signaling in the ipsilateral thigh was the most sensitive indicator of impaired muscle protein synthesis and failed strength recovery after 8 wk of usual care.
Progressive resistance exercise training (PRT) is a putative anabolic intervention that the investigators find consistently increases muscle mass to meet healthy standards in atrophied and mobility-impaired adults, by activating muscle protein synthesis and the myogenic activity of muscle satellite cells.
Together, these findings raise the central hypothesis that PRT plus adjunctive functional mobility training (PRT+FM) after THA/TKA will more effectively restore muscle mass and mobility function to healthy standards than usual care and, because MuIS(+) are predicted to suffer failed muscle recovery and persistent dismobility under usual care, the impact of PRT+FM will be greatest in MuIS(+).
The investigators will thoroughly test this hypothesis in a randomized controlled trial of 88 THA/TKA patients with the following aims.
Aim 1: To determine the effects of 16 wk of PRT+FM vs. usual care after elective THA/TKA on muscle mass, performance, and mobility function.
Aim 2: To determine whether MuIS status modifies the effects of PRT+FM or usual care after THA/TKA.
Cellular and molecular mechanisms of muscle mass regulation will be studied in detail.
Aim 3. To determine the long-term impact of 16 wk PRT+FM by re-assessing outcomes at 6 mo and 1 y.
The investigators fully expect the novel findings to lead a paradigm shift in THA/TKA rehabilitation that will have a profound impact on a growing segment of the population.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
80
Phase
- Unzutreffend
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
Alabama
-
Birmingham, Alabama, Vereinigte Staaten, 35205
- UAB Center for Exercise Medicine
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
40 Jahre bis 80 Jahre (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
Inclusion Criteria:
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).
Exclusion Criteria:
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.
- Any other condition or events considered exclusionary by the PIs and/or physician Co-Is.
- 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.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Single
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Experimental: PRT + FM
Progressive resistance training + functional mobility training 3 d/wk x 16 wk
|
Supervised progressive resistance training + functional mobility training (PRT+FM) 3 days per week for 16 weeks post-surgery.
Post-surgical usual care activities including any prescribed physical therapy
|
Aktiver Komparator: Usual Care
Post-surgical usual care including physical therapy
|
Post-surgical usual care activities including any prescribed physical therapy
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Change in unilateral (surgical) thigh muscle mass (unit of measure = grams)
Zeitfenster: Pre-surgery to 16 weeks post-surgery
|
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)
Zeitfenster: Pre-surgery to 16 weeks post-surgery
|
Primary functional outcome of Aim 1
|
Pre-surgery to 16 weeks post-surgery
|
Change in short physical performance battery (SPPB) (unit of measure = score)
Zeitfenster: From 16 weeks post-surgery to 26 and 52 weeks post-surgery
|
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)
Zeitfenster: At the time of surgery
|
Primary outcome of Aim 2: Muscle inflammation susceptibility (MuIS) defined by TWEAK receptor gene expression
|
At the time of surgery
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Change in muscle fiber size (unit of measure = micrometers squared)
Zeitfenster: From the time of surgery to 16 weeks post-surgery
|
From the time of surgery to 16 weeks post-surgery
|
Change in unilateral (surgical) knee extension isometric strength (unit of measure = Newton-meters)
Zeitfenster: Pre-surgery to 16 weeks post-surgery
|
Pre-surgery to 16 weeks post-surgery
|
Change in maximum 10-meter gait speed (unit of measure = meters per second)
Zeitfenster: Pre-surgery to 16 weeks post-surgery
|
Pre-surgery to 16 weeks post-surgery
|
Andere Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Change in free-living physical activity (unit of measure = steps per day)
Zeitfenster: Pre-surgery to 8, 16, 26, and 52 weeks post-surgery
|
Via wearable technology (i.e.
step counter)
|
Pre-surgery to 8, 16, 26, and 52 weeks post-surgery
|
Change in self-reported health status (unit of measure = score)
Zeitfenster: Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Via Short Form-36v2 Health Survey (SF-36v2)
|
Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Change in cellular and molecular markers (unit of measure = arbitrary units)
Zeitfenster: From the time of surgery to 16 weeks post-surgery
|
Experiments using muscle tissue and primary muscle satellite cells collected from surgical and contralateral limbs.
|
From the time of surgery to 16 weeks post-surgery
|
Change in fatigue (unit of measure = score)
Zeitfenster: Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Via Patient Reported Outcomes Measurement Information System (PROMIS)
|
Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Change in pain (unit of measure = score)
Zeitfenster: Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Via Patient Reported Outcomes Measurement Information System (PROMIS)
|
Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Change in depression (unit of measure = score)
Zeitfenster: Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Beck Depression Inventory (BDI II)
|
Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Change in fatigue severity (unit of measure = score)
Zeitfenster: Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Fatigue Severity Scale (FSS)
|
Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Mitarbeiter
Ermittler
- Hauptermittler: Marcas M Bamman, PhD, University of Alabama at Birmingham
- Hauptermittler: S Louis Bridges, MD, PhD, University of Alabama at Birmingham
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
1. Oktober 2015
Primärer Abschluss (Tatsächlich)
1. September 2020
Studienabschluss (Tatsächlich)
28. Februar 2021
Studienanmeldedaten
Zuerst eingereicht
5. August 2015
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
10. Dezember 2015
Zuerst gepostet (Schätzen)
11. Dezember 2015
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
7. Juli 2021
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
3. Juli 2021
Zuletzt verifiziert
1. Juli 2021
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- R01HD084124 (US NIH Stipendium/Vertrag)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
UNENTSCHIEDEN
Beschreibung des IPD-Plans
Data might be provided on written request in aggregate form.
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
Klinische Studien zur Arthrose
-
Anchen Pharmaceuticals, IncNovum Pharmaceutical Research ServicesAbgeschlossenOsteoarthritis des KniesVereinigte Staaten
-
University of PaviaNoch keine RekrutierungOsteoarthritis Knie und Hüfte | Endoprothetik der unteren ExtremitätenItalien
-
Washington University School of MedicineZimmer BiometAbgeschlossenOsteoarthritis-SchulternVereinigte Staaten
-
Boston UniversityNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Noch keine Rekrutierung
-
Mostafa BahaaRekrutierung
-
Centre Hospitalier Universitaire de NiceRekrutierungOsteoarthritis KnieFrankreich
-
Seoul National University Bundang HospitalMinistry of Health, Republic of KoreaRekrutierungOsteoarthritis KnieKorea, Republik von
-
University Hospital, GhentRekrutierungOsteoarthritis KnieBelgien
-
Riphah International UniversityAbgeschlossen
-
Istanbul Medipol University HospitalAbgeschlossen
Klinische Studien zur PRT + FM
-
Oulu University HospitalLoisto Terveys, Oulu; Fysios Kastelli, Oulu; Faskia-Markus, OuluAnmeldung auf EinladungSchmerzen im unteren Rücken | Rückenschmerzen, wiederkehrendFinnland
-
Stanford UniversityAnonymous DonorRekrutierungAutismus-Spektrum-Störung | Autismus | ASDVereinigte Staaten
-
C.B. Fleet Company, Inc.AbgeschlossenDarmreinigung vor der KoloskopieVereinigte Staaten
-
Yale UniversityAbgeschlossen
-
Stanford UniversityAbgeschlossenAutistische Störung | EntwicklungsstörungenVereinigte Staaten
-
University of Colorado, DenverVA Eastern Colorado Health Care SystemRekrutierungRückenschmerzen | Chronischer Schmerz | Nackenschmerzen | Chronische RückenschmerzenVereinigte Staaten
-
Jinyang LiAbgeschlossenSjögren-Syndrom-Patienten mit schwerem Trockenem AugeChina
-
University of AarhusAarhus University Hospital; Vejle Hospital; Regionshospitalet Silkeborg; Physiotherapy...Rekrutierung
-
Proteon TherapeuticsUniversity of California, San FranciscoAbgeschlossenPeriphere arterielle VerschlusskrankheitVereinigte Staaten
-
Proteon TherapeuticsAbgeschlossenEine Phase-1-2-Studie zu PRT-201 zur Anwendung bei Patienten mit chronischer Nierenerkrankung (CKD).Chronisches NierenleidenVereinigte Staaten