Effect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study
- Conditions
- Rheumatoid ArthritisOsteoarthritisSarcopenia
- Interventions
- Other: High load exercise typeBehavioral: Low load exercise type
- Registration Number
- NCT06480643
- Lead Sponsor
- Amsterdam UMC, location VUmc
- Brief 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.
- Detailed Description
Rationale: 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.
Objective: to explore effectivity, interaction and predictability of two types of exercise intervention in patients with RA, OA and SARC alone. The primary outcome of this study will be isokinetic muscle strength of the quadriceps in all three target groups.
Study design: two-arm parallel-group exploratory trial including a total of 69 patients: study population 23 patients with OA, 23 patients with RA and 23 patients with SARC alone (according to the revised European Working Group on Sarcopenia in Older People consensus definition (EWGSOP-II criteria, Cruz- Jentoft 2019).
Intervention: Exercise intervention for 3 times a week for 8 weeks.
Main study parameters/endpoints: the main study parameter is the difference in isokinetic muscle strength pre- and post-intervention in all three patient groups. The secondary study parameters include muscle endurance; mitochondrial respiration, gene and protein expression and histology via muscle biopsies; inflammation via bloodwork and feasibility.
Intervention: Exercise intervention for 3 times a week for 8 weeks.
Main study parameters/endpoints: the main study parameter is the difference in isokinetic muscle strength pre- and post-intervention in all three patient groups. The secondary study parameters include muscle endurance; mitochondrial respiration, gene and protein expression and histology via muscle biopsies; inflammation via bloodwork and feasibility.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 69
Not provided
- Body mass index (BMI) < 18 and > 35 Kg/m2
- Contra-indications for exercise testing and prescription as indicated by the ACSM guideline (i.e. progressive increase in heart failure symptoms, myocardial infarction less than three months before the start of the training programme, severe cardiac ischemia upon exertion, respiratory frequency of more than 30 breaths per minute and heart rate at rest >110 beats per minute).
- Participants taking beta-blockers for the duration of the intervention.
- Diagnosed with other neurologic or cachectic diseases or major surgery that may interfere with muscle quality (i.e. multiple sclerosis, ongoing cancer treatment or radiotherapy/ chemotherapy in the previous 6 months).
- Participating in another regular and intense (i.e. high physical loading training such as high-load circuit training for muscle gain and fat loss > 2 times a week) physical training programme within 2 months prior to enrolment.
- Ligament/muscle tear and/or other injuries within 6 months.
- Taking drugs (e.g. performance enhancing drugs) or nutritional supplements (e.g. protein powder) known to increase muscle mass.
- Inability to be scheduled for exercise therapy
- Insufficient comprehension of Dutch language or no informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High load exercise type High load exercise type The patients will perform 6-8 full-body exercises using a load of 60-75% of their 1RM. The exercises will comprise of both compound (multi-joint movement that works multiple muscle groups at the same time) and isolation (movement that targets a single muscle group and involves the movement of a single joint) exercises. Each training session will be preceded by a 3-5mins warm-up. Total exercise duration will vary between 45-60mins, comprising of 3 sets of 10 repetitions with 1 min periods of recovery. Patients will be required to maintain an intensity of 7-8 on a 10-point physical exertion scale Low load exercise type Low load exercise type Patients will perform 6-8 full-body exercises with a load of 30-45% of their 1RM. This training session will include both bodyweight and circuit training types. Each training session will be preceded by a 5-10mins warm-up. Total exercise duration will vary between 45-60mins (including the warm-up and cool down), with each exercise comprising of 3 sets of 20 repetitions with 1 min periods of recovery. A 5-min cool-down will follow the final rest period. Patients will be required to maintain an intensity of 7-8 on a 10-point physical exertion scale
- Primary Outcome Measures
Name Time Method Isokinetic muscle strength in Nm/kg Measured before and after the 8 week- exercise block. 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
- Secondary Outcome Measures
Name Time Method Muscle endurance in number of repetitions Measured before and after the 8 week- exercise block. 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.
Apoptosis & proteolysis Measured before the 8 week- exercise block. CASP1; CASP3; MURF1; MAFBX; BCL2; Gene + protein USP19
Mitochondrial biogenesis & function Measured before the 8 week- exercise block. PPARGC1A; mitochondrial complex I-V (Ci-Cv); NDUFA1, NDUFA2, SDHA, SHDB, UQCRC1, CYC1, COX4I1, COX5A, ATP5B, ATP5A1, CCO, C15ORF48
Glucose metabolism Measured before the 8 week- exercise block. GLUT4; SIRT1; FOXO1; AMPK-P
Oxidative stress & endogenous antioxidants Measured before the 8 week- exercise block. 3NT, Cys-S-NO, MDA\*, NOS, NOX, GTHP, GTHO \& SOD2; SOD1; CAT; HMOX1; NQO1; NRF2; GPX1
Cytokines Measured before and after the 8 week- exercise block TNFa; IL1b; IL6; IFNy \& myokines
Myogenesis Measured before the 8 week- exercise block. SETD3; MYOD1; MYOG
General inflammatory markers Measured before and after the 8 week- exercise block. CRP, ESR