Alterations in Muscle After Total Knee Arthroplasty
7. juni 2021 oppdatert av: University of Colorado, Denver
Alterations in Skeletal Muscle Gene Expression Following Total Knee Arthroplasty
The overall goals of this work are: 1) to elucidate alterations in gene expression and downstream protein synthesis 2 weeks after Total Knee Arthroplasty (TKA) to better explain quadriceps muscle atrophy after TKA and 2) understand the mechanisms responsible for improved maintenance of muscle strength with Neuromuscular Electrical Stimulation (NMES) utilization.
Furthermore, this investigation seeks to expand previous findings regarding attenuation of strength and functional performance deficits with NMES application to better understand how altered gene expression influences muscle function.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Forventet)
20
Fase
- Ikke aktuelt
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
Colorado
-
Aurora, Colorado, Forente stater, 80045
- University of Colorado School of Medicine
-
Aurora, Colorado, Forente stater, 80045
- Univeristy of Colorado Anschutz Medical Campus
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
50 år til 75 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- 50 to 75 years of age
- Scheduled for unilateral TKA at University of Colorado Hospital
- Diagnosed with osteoarthritis
- Cognitive status that allows patients to consistently comprehend and repeat back directions regarding the details of the study
Exclusion Criteria:
- Neurological, vascular or cardiac problems that significantly limit function
- BMI > 35
- Testosterone supplementation
- Pregnancy
- Anticoagulant therapy
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Enkelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Neuromuscular Electrical Stimulation
Neuromuscular Electrical Stimulation (NMES) 48 hours after TKA, 5x/week, 2x/day, for 45 minutes/session. Standard Rehabilitation Protocol |
5x/week, 2x/day, for 45 minutes/session
Standard physical therapy after TKA
|
|
Aktiv komparator: Control
Standard Rehabilitation Protocol
|
Standard physical therapy after TKA
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Catabolic gene expression
Tidsramme: Change in gene expression from immediately pre surgery to 2 weeks after surgery
|
Standard procedures including total RNA isolation, cDNA synthesis, cRNA labeling, microarray hybridization and image acquisition will be performed.
Protein content (translation of MAFbx, MuRF1, myostatin) will be analyzed.
Total RNA (500 ng) will be reverse transcribed with the iScript cDNA synthesis kit (Bio-Rad, Hercules, CA), and quantitative PCR will be performed using primer sets for genes of interest, reference genes and iQ SYBR Supermix (Bio-Rad) following manufacturer's protocols.
|
Change in gene expression from immediately pre surgery to 2 weeks after surgery
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Changes in quadriceps strength
Tidsramme: 3 days Pre operative and 2 weeks post operative
|
Isometric quadriceps strength will be using a doublet interpolation test performed by research assistants blinded to participants' treatment randomization.
Briefly, patients will be seated and stabilized in a HUMAC NORM (Computer Sports Medicine Incorporated, Stoughton, MA) dynamometer with their knee flexed to 60 degrees.
After proper warm up, patients will be asked to perform a maximum voluntary isometric contraction of their quadriceps while receiving verbal reinforcement.
|
3 days Pre operative and 2 weeks post operative
|
|
Changes in quadriceps size
Tidsramme: 3 days Pre operative and 2 weeks post operative
|
Peripheral Quantitative Computed Tomography scans of the distal femur will be used to assess the changes in quadriceps muscle morphology quantitatively.
The maximal cross-sectional area of the quadriceps will be determined prior to TKA and ~14 days after TKA by manually placing the scanner at a line marked on the vastus lateralis one third of the distance between the greater trochanter and the lateral epicondyle of the femur.
The pQCT software will analyze the image and calculate muscle cross-sectional area.
A previous investigation by Cramer, et al. validated the pQCT to measurement of muscle cross-sectional area by comparison to MRI and (R2 values of 0.979 and 0.983).
In addition, the use of the pQCT to measure muscle cross sectional area had high test-retest reliability, with ICC values of 0.996 and 0.998.
|
3 days Pre operative and 2 weeks post operative
|
|
Changes in quadriceps activation
Tidsramme: 3 days Pre operative and 2 weeks post operative
|
Isometric quadriceps activation testing will be using a doublet interpolation test performed by research assistants blinded to participants' treatment randomization.
Briefly, patients will be seated and stabilized in a HUMAC NORM (Computer Sports Medicine Incorporated, Stoughton, MA) dynamometer with their knee flexed to 60 degrees.
After proper warm up, patients will be asked to perform a maximum voluntary isometric contraction of their quadriceps while receiving verbal reinforcement.
During the contraction, a 2 pulse, 600 µs duration/pulse, supramaximal 100Hz stimulus will be delivered to the muscle to assess whether the subject is indeed maximally contracting the quadriceps muscle and again at rest.
|
3 days Pre operative and 2 weeks post operative
|
|
Functional Performance Measures (4 meter walk test, timed up and go, stair climbing test)
Tidsramme: 3 days Pre operative and 2 weeks post operative
|
The timed Stair Climbing Test (SCT) places a high demand on the quadriceps and therefore measures a higher level of function and, therefore, minimizes the possibility of a ceiling effect.
The SCT has been shown to significantly correlate to the Timed Up and Go (TUG).
The TUG measures the time it takes a patient to rise from an arm chair (seat height of 46 cm), walk 3 m, turn and return to sitting in the same chair without physical assistance.25
This test has excellent inter-rater (ICC=0.99)
and intra-rater reliability (ICC=0.99),
as measured in a group of 60 functionally disabled older adults (mean age 80 years).25
The 4 meter Walk Test (4mWT) will be assessed at the fastest safe speed for each participant.
|
3 days Pre operative and 2 weeks post operative
|
|
Anabolic Gene Expression
Tidsramme: Immediately pre surgery to 2 weeks after surgery
|
Standard procedures including total RNA isolation, cDNA synthesis, cRNA labeling, microarray hybridization and image acquisition will be performed.
Protein content (translation of mTOR, myogenin, and MyoD) will be analyzed.
Total RNA (500 ng) will be reverse transcribed with the iScript cDNA synthesis kit (Bio-Rad, Hercules, CA), and quantitative PCR will be performed using primer sets for genes of interest, reference genes and iQ SYBR Supermix (Bio-Rad) following manufacturer's protocols.
|
Immediately pre surgery to 2 weeks after surgery
|
|
Muscle Fiber Cross-Sectional Area
Tidsramme: Immediately pre surgery to 2 weeks after surgery
|
Cross sectional area of individual myofibrils taken from the vastus lateralis muscle using immunohistochemical staining and microscopy to determine change in cross sectional area comparing one hour before surgery to two weeks after surgery
|
Immediately pre surgery to 2 weeks after surgery
|
|
Changes in neural cell adhesion molecule (NCAM) concentration
Tidsramme: Preop and 2 weeks postop
|
NCAM will be assessed by immunohistochemistry with anti-CD56/NCAM antibody (555514; BD Biosciences, San Jose, CA), followed by goat anti-mouse AF555 (A-21127, ThermoFisher).
NCAM is a multifunctional cell-surface protein that has been shown to be associated with muscle regeneration, through its roles in neurite outgrowth and synaptic plasticity.
NCAM immunohistochemistry will be able to assess 1) denervation status, 2) skeletal muscle response to an intervention, and 3) the capacity for skeletal muscle to improve.
|
Preop and 2 weeks postop
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Hovedetterforsker: Victor Cheuy, PhD, University of Colorado, Denver
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. oktober 2014
Primær fullføring (Faktiske)
9. mars 2020
Studiet fullført (Faktiske)
9. mars 2020
Datoer for studieregistrering
Først innsendt
7. oktober 2014
Først innsendt som oppfylte QC-kriteriene
30. oktober 2014
Først lagt ut (Anslag)
4. november 2014
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
9. juni 2021
Siste oppdatering sendt inn som oppfylte QC-kriteriene
7. juni 2021
Sist bekreftet
1. juni 2021
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 14-0905
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .