- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT02281877
Alterations in Muscle After Total Knee Arthroplasty
7 juni 2021 uppdaterad 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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Förväntat)
20
Fas
- Inte tillämpbar
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
Colorado
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Aurora, Colorado, Förenta staterna, 80045
- University of Colorado School of Medicine
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Aurora, Colorado, Förenta staterna, 80045
- Univeristy of Colorado Anschutz Medical Campus
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-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
50 år till 75 år (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Enda
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: 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
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Standard physical therapy after TKA
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Catabolic gene expression
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Changes in quadriceps strength
Tidsram: 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.
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3 days Pre operative and 2 weeks post operative
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Changes in quadriceps size
Tidsram: 3 days Pre operative and 2 weeks post operative
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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.
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3 days Pre operative and 2 weeks post operative
|
Changes in quadriceps activation
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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
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Changes in neural cell adhesion molecule (NCAM) concentration
Tidsram: 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.
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Preop and 2 weeks postop
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Huvudutredare: Victor Cheuy, PhD, University of Colorado, Denver
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 oktober 2014
Primärt slutförande (Faktisk)
9 mars 2020
Avslutad studie (Faktisk)
9 mars 2020
Studieregistreringsdatum
Först inskickad
7 oktober 2014
Först inskickad som uppfyllde QC-kriterierna
30 oktober 2014
Första postat (Uppskatta)
4 november 2014
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
9 juni 2021
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
7 juni 2021
Senast verifierad
1 juni 2021
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 14-0905
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