Effect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study
NCT Number: NCT06480643
Acronym: C4M
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Rheumatoid Arthritis|Osteoarthritis|Sarcopenia
Interventions: OTHER: High load exercise type|BEHAVIORAL: Low load exercise type
Sponsor: Amsterdam UMC, location VUmc
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 69
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: PREVENTION
Start Date: 2024-12-01
Completion Date: 2027-10-31

Summary:
C4M hypothesizes that patients with low muscle strength may respond differently to different types of exercise intervention, dependent on the underlying aetiology, i.e. impaired protein synthesis versus metabolic dysfunction and that this response is predictable based on the clinical diagnosis, i.e. rheumatoid arthritis (RA), osteoarthritis (OA) and Sarcopenia alone (SARC) and a number of clinical, blood based and muscle metabolic and architectural biomarkers. Understanding the underlying biochemical response of each patient group to the different type of exercise loading could help with the development of disease-specific training, making it more effective and more predictable on outcomes.

Primary Outcome Measures: Isokinetic muscle strength in Nm/kg, Maximal net joint moment measurements of muscle strength will be assessed using an isokinetic dynamometer (EnKnee, Enraf-Nonius, Rotterdam, the Netherlands). An initial practice attempt will be used for familiarization. Participants will perform three maximal test repetitions to measure the isokinetic strength of the quadriceps and hamstrings for each knee, at 60°/s. Mean quadriceps and hamstring muscle strength per leg will be calculated (in Nm) and divided by the participant's weight (in kg). Muscle strength data (in Nm/kg) of the index knee (most affected knee) will be used (de Zwart 2022). The 1-RM will be defined as the maximal weight in kg a patient could lift for only one repetition, Measured before and after the 8 week- exercise block.
Secondary Outcome Measures: Muscle endurance in number of repetitions, this will be measured by the knee extension test of both legs using an isokinetic dynamometer (EnKnee, Enraf-Nonius, Rotterdam, the Netherlands). The patients will be asked to perform the knee extension exercise at 30% 1RM until muscular failure. The number of repetitions obtained until muscular failure will be the indication of muscle endurance., Measured before and after the 8 week- exercise block.|Myogenesis, SETD3; MYOD1; MYOG, Measured before the 8 week- exercise block.|Apoptosis & proteolysis, CASP1; CASP3; MURF1; MAFBX; BCL2; Gene + protein USP19, Measured before the 8 week- exercise block.|Oxidative stress & endogenous antioxidants, 3NT, Cys-S-NO, MDA\*, NOS, NOX, GTHP, GTHO \& SOD2; SOD1; CAT; HMOX1; NQO1; NRF2; GPX1, Measured before the 8 week- exercise block.|Mitochondrial biogenesis & function, PPARGC1A; mitochondrial complex I-V (Ci-Cv); NDUFA1, NDUFA2, SDHA, SHDB, UQCRC1, CYC1, COX4I1, COX5A, ATP5B, ATP5A1, CCO, C15ORF48, Measured before the 8 week- exercise block.|Glucose metabolism, GLUT4; SIRT1; FOXO1; AMPK-P, Measured before the 8 week- exercise block.|General inflammatory markers, CRP, ESR, Measured before and after the 8 week- exercise block.|Cytokines, TNFa; IL1b; IL6; IFNy \& myokines, Measured before and after the 8 week- exercise block
Other Outcome Measures: Age in years, Subject characteristic, Measured before 8 week- exercise block.|Gender (male or female), Subject characteristic, Measured before 8 week- exercise block.|Height in centimetres, Subject characteristic, Measured before and after the 8 week- exercise block.|Weight in kilgorams, Subject characteristic, Measured before and after the 8 week- exercise block.|Co-morbidities, If any is present, Measured before 8 week- exercise block.|Medication, Any current medication use or medication use in the past 3-6 months will be recorded., Measured before 8 week- exercise block.|Educational level, Highest level of education received, Measured before 8 week- exercise block.|Employment status, Employed or unemployed, Measured before 8 week- exercise block.|Marital status, Single, married, divorce, widow etc., Measured before 8 week- exercise block.|Smoking use, Smoking yes or no, Measured before 8 week- exercise block.|Smoking frequency per day, If patients smoke, the amount of cigarettes per day, Measured before and after the 8 week- exercise block.|Alcohol frequency, If patients drink, the frequency in a day/week, Measured before and after the 8 week- exercise block.|Alcohol use, Alcohol yes or no, Measured before and after the 8 week- exercise block.|BMI in kg/m^2, Anthropometric, Measured before and after the 8 week- exercise block.|Absolute & relative muscle mass in kilograms, InBody S10, Biospace Co., Ltd, Seoul, South Korea) will be used to measure muscle mass. DSM-BIA has been validated for assessing segmental and whole-body composition against dual energy X-ray absorptiometry (DEXA) (Ling 2011). DSM-BIA will not be performed in patients with 1) electronic internal medical devices or implants such as cardiac pacemakers; 2) plasters or bandages interfering with the placement of the electrodes; 3) amputation., Measured before and after the 8 week- exercise block.|Short-form mini-nutritional assessment, Anthropometrics, Measured before and after the 8 week- exercise block.|Handgrip strength in kilograms, A hand-held dynamometer (JAMAR, Sammons Preston, Inc., 119 Bolingbrook, IL, USA will be used to measure handgrip strength. Subjects will be in a sitting position with elbows flexed at 90 degrees, shoulders adducted and forearms in a neutral position without support and instructed to squeeze the dynamometer maximally three times for each hand, alternating between the right and the left- hand side. Maximal value will be reported in kg., Measured before and after the 8 week- exercise block.|Short physical performance battery test (score 0-12), The total score of the SPPB is the sum of the number of points achieved (range between 0 and 12) in each of the test components. The higher the score, the better the patient's performance. Persons with a score between 4 and 9 have an increased risk of new disabilities and are therefore a suitable target group for interventions to improve functioning. People with a higher score are not yet in the danger zone. People with a lower score already experience many limitations and are therefore more likely to be eligible for interventions to maintain functioning and possibly deal with limitations., Measured before and after the 8 week- exercise block.|6 minutes walk test in metres, The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity., Measured before and after the 8 week- exercise block.|FitMáx© survey in score, The FitMáx© is a questionnaire consisting of three single answer questions, about the maximum capacity of walking, climbing stairs and cycling. The questionnaire consists of a scale from 0-13 to rate maximum capacity of walking, a scale from 0-11 for maximum capacity of cycling and for the maximum capacity of stair climbing a scale from 0-10 is used., Measured before and after the 8 week- exercise block.|Patient-Reported Outcome Measures (PROMs), PROMIS-CAT short forms will be used to self-report of core symptoms and health-related quality of life according to the Item Response Theory. We will assess the domains pain, fatigue, physical function, social function (Witter 2016), Measured before and after the 8 week- exercise block.|Muscle volume in m^2, Muscle volume will be measured between the origin and distal end of the muscle belly using manual segmentation of the anatomical cross-sections and interpolation in custom software. Average fascicle length (ℓfasc) and pennation angles (αfasc) will be estimated., Measured before and after the 8 week- exercise block.|Average fascicle length (ℓfasc), Muscle volume will be measured between the origin and distal end of the muscle belly using manual segmentation of the anatomical cross-sections and interpolation in custom software. Average fascicle length (ℓfasc) and pennation angles (αfasc) will be estimated., Measured before and after the 8 week- exercise block.|Pennation angles (αfasc), Muscle volume will be measured between the origin and distal end of the muscle belly using manual segmentation of the anatomical cross-sections and interpolation in custom software. Average fascicle length (ℓfasc) and pennation angles (αfasc) will be estimated., Measured before and after the 8 week- exercise block.|Muscle physiological cross-sectional area (PCSA), PCSA will be calculated by dividing muscle volume by ℓfasc. Muscle volume and PCSA will are prime determinants of maximal muscle power and muscle strength, respectively., Measured before and after the 8 week- exercise block.