Effect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study

NCT06480643 | Not Yet Recruiting DMC

• 1 other identifier: 86908
• Study Type: interventional
• Target: 69
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Rheumatoid Arthritis; Osteoarthritis; Sarcopenia

Keywords

exercise therapy; RMD; strength training; muscle endurance; rheumatoid arthritis; osteoarthritis; sarcopenia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Muscle endurance in number of repetitions

  Measured before and after the 8 week- exercise block.

• Myogenesis

  Measured before the 8 week- exercise block.

• Apoptosis & proteolysis

  Measured before the 8 week- exercise block.

• Oxidative stress & endogenous antioxidants

  Measured before the 8 week- exercise block.

• Mitochondrial biogenesis & function

  Measured before the 8 week- exercise block.

Other Outcomes (25)

• Age in years

  Measured before 8 week- exercise block.

• Gender (male or female)

  Measured before 8 week- exercise block.

• Height in centimetres

  Measured before and after the 8 week- exercise block.

Study Arms (2)

High load exercise type

EXPERIMENTAL

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

Other: High load exercise type

Low load exercise type

EXPERIMENTAL

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

Behavioral: Low load exercise type

Interventions

High load exercise type OTHER

Heavier load, fewer reps

High load exercise type

Low load exercise type BEHAVIORAL

Lighter load, more reps

Low load exercise type

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Low muscle strength defined as hand grip strength (HGS) \<27 kg and \<16 kg for males and females respectively. If HGS is not possible due to interfering pain or joint- deformity, the chair stand test is used instead, with low muscle strength defined as not able to rise from the chair without arms or a time \>15 sec (Cruz Jentoft 2019).
• Gait speed of \>0.8m/s to exclude patients who are too disabled to participate in the study (Cruz Jentoft 2019).
• OA patients
• Age between 50 and 70
• Patients with either knee and/or hip OA according to clinical American College of Rheumatology (ACR) criteria (Altman 1986).
• Kellgren and Lawrence grading score of 2-4 for hip and/or knee OA (Altman 1991).
• C-reactive Protein (CRP) levels \<10mg/L within 3 months prior to enrolment (Sanchez 2014).
• Rheumatoid arthritis patients
• Age between 50 and 70
• Diagnosed with RA according to European Alliance of Associations for Rheumatology (EULAR)/ACR criteria (Aletaha 2010).
• Disease activity score in 28 joints (DAS28) 2.8\<5.6, as defined by the EULAR criteria (Aletaha 2010), either de novo or despite Disease-Modifying Antirheumatic Drug therapy.
• Stable disease three months prior to the start of the exercise intervention.
• Stable rheumatic medication three months prior to the start of the exercise intervention.
• Stopped the usage of corticosteroids 3 months prior to the start of the exercise intervention.
• Disease duration \>1 year and \<15 years

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Related Publications (11)

• Dardevet D, Remond D, Peyron MA, Papet I, Savary-Auzeloux I, Mosoni L. Muscle wasting and resistance of muscle anabolism: the "anabolic threshold concept" for adapted nutritional strategies during sarcopenia. ScientificWorldJournal. 2012;2012:269531. doi: 10.1100/2012/269531. Epub 2012 Dec 23.

  PMID: 23326214 BACKGROUND

• Bao W, Sun Y, Zhang T, Zou L, Wu X, Wang D, Chen Z. Exercise Programs for Muscle Mass, Muscle Strength and Physical Performance in Older Adults with Sarcopenia: A Systematic Review and Meta-Analysis. Aging Dis. 2020 Jul 23;11(4):863-873. doi: 10.14336/AD.2019.1012. eCollection 2020 Jul.

  PMID: 32765951 BACKGROUND

• Ganz DA, Latham NK. Prevention of Falls in Community-Dwelling Older Adults. N Engl J Med. 2020 Feb 20;382(8):734-743. doi: 10.1056/NEJMcp1903252. No abstract available.

  PMID: 32074420 BACKGROUND

• Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019 Apr 27;393(10182):1745-1759. doi: 10.1016/S0140-6736(19)30417-9.

  PMID: 31034380 BACKGROUND

• Hanaoka BY, Ithurburn MP, Rigsbee CA, Bridges SL Jr, Moellering DR, Gower B, Bamman M. Chronic Inflammation in Rheumatoid Arthritis and Mediators of Skeletal Muscle Pathology and Physical Impairment: A Review. Arthritis Care Res (Hoboken). 2019 Feb;71(2):173-177. doi: 10.1002/acr.23775. Epub 2019 Jan 4.

  PMID: 30295435 BACKGROUND

• van Vilsteren M, Boot CR, Knol DL, van Schaardenburg D, Voskuyl AE, Steenbeek R, Anema JR. Productivity at work and quality of life in patients with rheumatoid arthritis. BMC Musculoskelet Disord. 2015 May 6;16:107. doi: 10.1186/s12891-015-0562-x.

  PMID: 25940578 BACKGROUND

• Chen L, Nelson DR, Zhao Y, Cui Z, Johnston JA. Relationship between muscle mass and muscle strength, and the impact of comorbidities: a population-based, cross-sectional study of older adults in the United States. BMC Geriatr. 2013 Jul 16;13:74. doi: 10.1186/1471-2318-13-74.

  PMID: 23865675 BACKGROUND

• Mayhew AJ, Amog K, Phillips S, Parise G, McNicholas PD, de Souza RJ, Thabane L, Raina P. The prevalence of sarcopenia in community-dwelling older adults, an exploration of differences between studies and within definitions: a systematic review and meta-analyses. Age Ageing. 2019 Jan 1;48(1):48-56. doi: 10.1093/ageing/afy106.

  PMID: 30052707 BACKGROUND

• Helliwell PS, Jackson S. Relationship between weakness and muscle wasting in rheumatoid arthritis. Ann Rheum Dis. 1994 Nov;53(11):726-8. doi: 10.1136/ard.53.11.726.

  PMID: 7826134 BACKGROUND

• Lemmey AB, Wilkinson TJ, Clayton RJ, Sheikh F, Whale J, Jones HS, Ahmad YA, Chitale S, Jones JG, Maddison PJ, O'Brien TD. Tight control of disease activity fails to improve body composition or physical function in rheumatoid arthritis patients. Rheumatology (Oxford). 2016 Oct;55(10):1736-45. doi: 10.1093/rheumatology/kew243. Epub 2016 Jun 10.

  PMID: 27288209 BACKGROUND

• Steinz MM, Persson M, Aresh B, Olsson K, Cheng AJ, Ahlstrand E, Lilja M, Lundberg TR, Rullman E, Moller KA, Sandor K, Ajeganova S, Yamada T, Beard N, Karlsson BC, Tavi P, Kenne E, Svensson CI, Rassier DE, Karlsson R, Friedman R, Gustafsson T, Lanner JT. Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis. JCI Insight. 2019 Mar 28;5(9):e126347. doi: 10.1172/jci.insight.126347.

  PMID: 30920392 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid; Osteoarthritis; Sarcopenia

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Central Study Contacts

Carel Meskers Prof.Dr.

CONTACT

+31 020-4440763; c.meskers@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head researcher

Model Details: two-arm parallel-group exploratory trial including a total of 69 patients

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 28, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: June 28, 2024

Record last verified: 2024-06