Muscle Wasting and Rheumatoid Arthritis Flares

May 1, 2024 updated by: Leeds Beckett University

Preventing Muscle Wasting During Rheumatoid Arthritis Flares: A Randomised Controlled Trial

People living with Rheumatoid Arthritis (RA) often present with low muscle mass compared to their healthy counterparts. This affects their mobility, overall health and quality of life. Even though low muscle mass in RA has been recognised for decades, it is still highly prevalent and very little is known about its development, progression, and potential management.

The researchers hypothesise that flares of disease activity trigger acute events of muscle wasting due to high inflammation and reduced mobility. This is commonly observed in bed rest studies and people hospitalised for various reasons. If this holds true for RA, it would point towards a stepwise development of RC and potentially allow for time-targeted management of it.

A potential method to manage it is through the use of nutritional supplements. Specifically, amino acid supplementation (commonly used by athletes or people wanting to increase muscle mass) during and shortly after a flare may counteract some of the muscle wasting and allow for better long-term mobility and quality of life for people living with RA.

This study aims to investigate aspects of muscle health changes following a disease flare-up in people with Rheumatoid Arthritis (RA) and test potential interventions to minimise any such changes. The investigators will randomly assign participants to a standard care or a nutritional supplementation group and assess aspects of body composition, muscle health, disease activity and inflammation on five occasions over a 3-month period.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study aims to investigate aspects of muscle health changes following a disease flare-up in people with Rheumatoid Arthritis (RA) and test potential interventions to minimise any such changes.

RA is the most common inflammatory arthritis manifesting mainly as joint swelling and pain, limiting mobility, and eventually leading to loss of functional capacity. RA also has severe extra-articular manifestations [1], affecting several tissues in the body including skeletal muscle [2]. People living with RA often present with an adverse body composition profile compared to the general population, characterised by low muscle mass at the presence of unchanged or even increased overall weight [3]. This condition, termed Rheumatoid Cachexia, may affect up to 2 out of 3 people with RA and associates with active disease, further reductions in mobility, and low quality of life [4].

While rheumatoid cachexia has been studied extensively, the course of its development, as well as potential causes or contributors to it are poorly understood. Inflammation, [5] as well as lifestyle factors, such as energy intake and physical activity, may contribute to the observed body composition changes [6].

People living with RA often experience flares of disease activity, where high levels of inflammation, cause an acute exaggeration of symptoms, leading to very low levels of mobility. This is commonly treated with corticosteroid injections which will rapidly reduce inflammation and allow the patient to regain mobility. However, that short period of high inflammatory load and low mobility may acutely affect muscle characteristics. Indeed, critically ill patients may lose up to 2% of skeletal muscle per day during the first week of hospitalisation [7]. This rapid decline in muscle health has been recently termed Acute sarcopenia (AS) by the European working group in sarcopenia and older persons (EWGSOP) [8]. Furthermore, recent work within this research team is currently under review (Aldrich et al., 2023 under review) demonstrating the rapid decline of muscle mass and quality in people suffering with various diseases. Additionally, corticosteroids themselves may further contribute to muscle wasting in RA [9]. Yet, the acute effects of flares and their treatment on muscle health in people with RA are not known.

Acute deterioration of muscle health following a flare may point towards a stepwise development of rheumatoid cachexia, i.e., bouts of acute deterioration that accumulate over time in steps rather than a continuous slow loss - which is the current understanding for the development of sarcopenia, the age-related muscle wasting. This would allow for target and potentially short-term interventions that could limit or even reverse muscle deterioration during a flare and help people with RA better maintain their functionality.

Exercise, and particularly resistance exercise, is the most effective way to increase muscle mass, strength, and quality. However, people during and shortly after a flare may not be willing to engage in such an intervention. Additional complexities around gym or home-based delivery, familiarisation, and safe execution render this a complex intervention with potentially limited applicability.

Nutritional supplementation on the other hand, is readily available, relatively cheap, and easy to administer. Specifically, for muscle health, amino acid supplementation, and particularly with leucine, has been shown to improve muscle mass and muscle function in older men and women [10]. Moreover, previous research has shown that these amino acid supplements do not suppress appetite, are well tolerated and easy to consume. Finally, recent unpublished data from this laboratory suggest that amino acid concentrations in the blood following consumption alongside a meal remain elevated vs placebo for over 2 hours. This indicates that consuming two supplements per day would provide sufficient amino acids to induce beneficial effects on muscle health.

Therefore, the aims of this investigation are:

  1. To understand the effects of acute RA flares on muscle health
  2. To assess the efficacy of amino acid supplementation vs. standard care in maintaining muscle health

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of a flare of rheumatoid arthritis

Exclusion Criteria:

  • Consultation with RA physician greater than 7 days before
  • Allergic to supplement ingredients
  • Other health conditions that affect muscle wasting; such as cancer and fibromyalgia
  • Previous joint replacement surgery within the last 6 months
  • Anyone with underlying kidney conditions
  • Currently partaking in other research projects involving treatments, exercise or nutritional interventions for rheumatoid arthritis
  • Patients who may be pregnant
  • Patients who are unable to provide their own informed consent
  • Patients who are unable to speak or understand English
  • Participants who have a diagnosis of dementia or Alzheimer's disease
  • Disabled participants who require wheelchair access

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard Care
This 'control' group will receive standard care following a flare of rheumatoid arthritis.
Experimental: Nutritional Supplementation
This 'intervention' group will receive a 4-week intervention involving twice daily consumption of amino acid supplements.
Dietary supplement: Amino Acid Supplement
The intervention lasts 4-week following the rheumatoid arthritis flare. It requires twice daily consumption of amino acid supplements alongside the breakfast and lunch time meals.
Other Names:
  • Amino Acid Gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lean Tissue Mass
Time Frame: Scans will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Whole-body composition will be assessed by dual energy x-ray absorptiometry scans and this will provide a value for lean tissue (muscle mass) in kilograms.
Scans will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quadriceps Lean Tissue Mass
Time Frame: Scans will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Quadriceps lean tissue mass will be assessed by dual energy x-ray absorptiometry scans focussed in the quadriceps region. Lean tissue mass in this region will be provided in kilograms.
Scans will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Rectus Femoris Cross-sectional Area
Time Frame: Scans will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Rectus femoris will be assessed by ultrasound scans. The muscle belly will be imaged and cross-sectional area will be calculated from this image (cm2).
Scans will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Handgrip Strength
Time Frame: Strength tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Upper-body muscle strength will be assessed by handgrip dynamometry and the value will be recorded in kilograms.
Strength tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Knee Extensor Strength
Time Frame: Strength tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Lower-body muscle strength will be assessed on a seated knee extension resistance machine and the highest value achieved will be recorded in kilograms.
Strength tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Short Physical Performance Battery
Time Frame: Muscle function tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Muscle function will be assessed by the Short Physical Performance Battery. This battery includes measures of gait speed, lower-limb strength/functionality and balance. The score of all tests is combined to provide a total score where a higher score indicates better muscle function.
Muscle function tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Timed Up and Go
Time Frame: Muscle function tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Muscle function will be assessed by the Timed Up and Go Test. This test assesses mobility and balance. The time taken to complete standing, walking 3-metres, then returning to sit down is recorded and a shorter time indicates better functionality.
Muscle function tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
6-minute Walk Test
Time Frame: Muscle function tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Muscle function will be assessed by the 6-Minute Walk Test. This test assesses endurance and aerobic capacity. The total distance walked in 6 minutes is recorded and a higher score indicates greater aerobic capacity.
Muscle function tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Plasma Amino Acid Content
Time Frame: Blood tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Blood plasma amino acid content (μmol/L) will be assessed at all time points using liquid chromatography mass spectrometry.
Blood tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Serum Steroid Hormone Content
Time Frame: Blood tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Blood serum steroid hormone content (ng/ml) will be assessed at all time-points using liquid chromatography mass spectrometry.
Blood tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Serum Vitamin D Content
Time Frame: Blood tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Blood serum vitamin D content (ng/ml)will be assessed at all time-points using liquid chromatography mass spectrometry.
Blood tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Diet Recall
Time Frame: 24-hour diet recall tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Participants will be asked to recall their dietary intake over the preceding 24 hours to determine calorie intake.
24-hour diet recall tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Physical Activity
Time Frame: 24-hour diet recall tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Physical activity habits will be assessed using the International Physical Activity Questionnaire (IPAQ) (short version). Time spent sitting, walking and exercising at various intensities will be recorded in days and hours.
24-hour diet recall tests will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Physical Ability, Social Support and Interaction, Pain, Health & Mood (Quality of Life - Rheumatoid Arthritis-Specific)
Time Frame: Quality of life assessments will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Quality of life will be assessed using the established Rheumatoid Arthritis quality of life (RAQoL) questionnaire. This will be assessed from a series of questions which will require answers ranked from 1 (very poor) to excellent (10).
Quality of life assessments will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Social Interaction & Pain (Quality of Life - PROMIS-29)
Time Frame: Quality of life assessments will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.
Quality of life will be assessed using the Patient Reported Outcome Measures Information System (PROMIS-29) questionnaire. This will assess physical function, anxiety, depression, fatigue, sleep disturbance, ability to take part in social roles and activities, pain interference and pain intensity. All answers will be on a scale from 1 to 5 except for pain intensity which is recorded on a scale from 1 to 10. Lower scores indicate negative answers except for questions regarding physical function and pain intensity.
Quality of life assessments will take place at baseline and 1-week, 2-weeks, 4-weeks and 12-weeks after baseline.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leeds Beckett University

Investigators

  • Study Chair: Theocharis Ispoglou, PhD, Leeds Beckett University
  • Study Chair: Oliver Wilson, PhD, Leeds Beckett University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 13, 2024

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

January 4, 2024

First Submitted That Met QC Criteria

May 1, 2024

First Posted (Actual)

May 6, 2024

Study Record Updates

Last Update Posted (Actual)

May 6, 2024

Last Update Submitted That Met QC Criteria

May 1, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 335887

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Participant data will be anonymised and kept within the current research group. Participant data will not be shared with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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