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

NCT ID: NCT06480643

Last Updated: 2024-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

69 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-01

Study Completion Date

2027-10-31

Brief Summary

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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

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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.

Conditions

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Rheumatoid Arthritis Osteoarthritis Sarcopenia

Keywords

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exercise therapy RMD strength training muscle endurance rheumatoid arthritis osteoarthritis sarcopenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

two-arm parallel-group exploratory trial including a total of 69 patients
Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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

Group Type EXPERIMENTAL

High load exercise type

Intervention Type OTHER

Heavier load, fewer reps

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

Group Type EXPERIMENTAL

Low load exercise type

Intervention Type BEHAVIORAL

Lighter load, more reps

Interventions

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High load exercise type

Heavier load, fewer reps

Intervention Type OTHER

Low load exercise type

Lighter load, more reps

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* 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

Sarcopenia patients

* Age between 50 and 80.
* Sarcopenia without joint involvement (no OA, RA), according to the EWGSOPII criteria (Cruz Jentoft 2019) of low muscle strength defined as HGS \<27kg and \<16 kg for males and females respectively (dynapenia). This group will therefore primarily involve participants with probable sarcopenia (dynapenia) but may also encompass participants with confirmed sarcopenia (appendicular muscle Lean Mass (ALM)/height2 \<7.0 kg/m2 for males and \<5.5 kg/m2 for females) as this is not a selection criterion. Severe sarcopenia will be excluded (gait speed \<0,8 m/s).
* Exclude patients with joint complaints (RA, OA, or other joint disease).

Exclusion Criteria

* 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.
Minimum Eligible Age

50 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amsterdam UMC, location VUmc

OTHER

Sponsor Role lead

Responsible Party

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Maia Sobejana

Head researcher

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Carel Meskers Prof.Dr.

Role: CONTACT

Phone: +31 020-4440763

Email: [email protected]

References

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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.

Reference Type BACKGROUND
PMID: 23326214 (View on PubMed)

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.

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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.

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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.

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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.

Reference Type BACKGROUND
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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.

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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.

Reference Type BACKGROUND
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Other Identifiers

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86908

Identifier Type: -

Identifier Source: org_study_id