Chronic Liver DiseaseNCT04734496
Evaluation of the Mechanisms of Sarcopenia in Chronic Inflammatory Disease: Protocol for a Prospective Cohort Study
An observational study of Chronic Liver Disease and Rheumatoid Arthritis, run by University of Birmingham at 1 site in United Kingdom.
Trial summary
Prospective, observational study to assess sarcopenia across three chronic inflammatory diseases: chronic liver disease, Inflammatory Bowel Disease, Rheumatoid Arthritis both before and after therapeutic intervention (standard of care treatment i.e. nutrition/exercise; biologic for IBD etc). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Liver Disease, Rheumatoid Arthritis, Inflammatory Bowel Diseases
- How many people
- 170 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jan 2019to 1 Sep 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Chronic liver disease patients will be selected from those who undergo assessment for liver transplantation . A Non-alcoholic fatty liver disease (NAFLD) subset will be screened and recruited from the NAFLD clinic. For Inflammatory bowel disease and Rheumatoid Arthritis, all patients commencing a new biologic treatment (via biologic clinic screening or biologic registry screening) will be screened prior to therapy commencement.
Who may be able to join
- A formal confirmed diagnosis of their underlying chronic inflammatory condition:
- Inflammatory bowel disease cohort patients will have endoscopic or radiological evidence.
- Some of the Chronic liver disease cohort will have had a liver biopsy, serological and radiological confirmation will be sufficient.
- RA cohort, clinical, serological and radiological confirmation will be sufficient.
- Biologic therapy naïve on recruitment or commencing a new biologic if in the IBD or IA cohort.
- Adults aged ≥ 18 years
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- Able to confirm written consent to the study
- Biologic therapy naïve on recruitment or commencing a new biologic if in the IBD or RA cohort Pre-existing or current use of immunosuppressant agents or Disease Modifying Antirheumatic Drugs (DMARDs) are acceptable in all cohorts.
- Meeting ACR (American College of Rheumatology) /EULAR (European League Against Rheumatism) 2010 or ACR 1987 Criteria for rheumatoid arthritis and starting DMARD therapy.
- Meeting criteria of an inflammatory arthritis as per the American College of Rheumatology
- Meeting criteria of liver cirrhosis including all Child Pugh scores from A-C as per British Association for the Study of the Liver guidance.
- Meeting criteria for Inflammatory bowel disease as per the British Society of Gastroenterology guidance.
- For muscle biopsy sampling (does not preclude patients from participating if they do not meet the below criteria) INR ≤ 1.6 Platelet count > 30
Who cannot join
- Refusal or lack capacity to give informed consent.
- Currently enrolled in an interventional trial with active treatment for their chronic disease condition.
- Previously undergone LT or biliary intervention in the Chronic liver disease cohort.
- Underlying or active cancer.
- Biliary intervention if Chronic liver disease
- For Muscle biopsies only (able to continue in study):
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- Obvious injury to both thighs.
- Active bleeding of site, pre-procedure,
- Abnormal observation parameters.
- Acute illness.
- INR > 1.6.
- Platelet count < 30.
- Anticoagulation which cannot be paused due to increased risk to pre-existing co-morbidity.
- For undergoing an Magnetic resonance imaging (MRI)
- Pacemaker.
- Metal work inserted that is not MRI compatible or further information cannot be obtained.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Institute of Inflammation and Ageing (IIA) University of Birmingham Research Laboratories
Birmingham, West Midlands, B15 2WB
About this study
Official title: Evaluation of Mechanisms of Sarcopenia in Chronic Inflammatory Disease (Chronic Liver Disease, Inflammatory Bowel Disease and Inflammatory Arthritis) Pre and Post Standard of Care Intervention; an Observational Study
Prospective, observational study to assess sarcopenia across three chronic inflammatory diseases: chronic liver disease, Inflammatory Bowel Disease, Rheumatoid Arthritis both before and after therapeutic intervention (standard of care treatment i.e. nutrition/exercise; biologic for IBD etc).
Read the detailed description
Introduction: Several chronic inflammatory diseases co-exist with and accelerate sarcopenia (reduction in muscle strength, quantity and quality) and negatively impact on both morbidity and mortality. There is limited research on the extent of sarcopenia in such conditions, how to accurately assess it and whether there are generic or disease specific mechanisms driving sarcopenia.
Methods: This prospective cohort study is unique; it provides a multi-modal approach to assess sarcopenia across three chronic inflammatory diseases: chronic liver disease, Inflammatory Bowel Disease, Rheumatoid Arthritis both before and after therapeutic intervention. A total of 170 patients will be recruited (50 with Chronic liver disease, 20 with non-cirrhotic nonalcoholic fatty liver disease, 50 with Inflammatory Bowel Disease and 50 with Rheumatoid Arthritis) and including a comparison cohort of n=20 age-sex matched healthy individuals.
Participants will undergo 4 assessments at defined time points; weeks 0, 2, 12 and 24, with blood tests to assess endocrine and inflammatory status; anthropometric (hand grip strength; mid-arm muscle circumference; triceps skinfold thickness); functional testing (short physical performance battery and isokinetic dynamometry); imaging ( ultrasound and Magnetic Resonance Imaging of the quadriceps), and vastus lateralis muscle biopsy. Physical activity and sleep will be monitored using actigraphy, and quality of life via questionnaires. Food diaries for nutritional intake analysis will be sampled between 0-2, 12 and 24 weeks. Stool and urine samples will be sampled for future microbiome and metabolomics analysis, respectively.
This study will identify mechanisms across the groups and within each cohort, to further target interventions to reduce sarcopenia in the future. This is the first study to use a multi modal assessment to characterise sarcopenia in chronic disease. The multi-modal assessment includes serological, anatomical, functional and histological analyses to evaluate the deep phenotyping of these patients. The observational study of small sample sizes will allow potential future targets for intervention.
- Being tested
- National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines)
- Medical subject headings
- Arthritis, Rheumatoid, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines)Other
National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines)
| Study group | Role | What they receive |
|---|---|---|
| Chronic Liver Disease | Patients with end-stage liver disease. Standard of care treatment will be nutrition and exercise as per European Association Study of Liver nutrition guidelines. Receives: Other: National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines) | |
| Rheumatoid Arthritis/Psoriatic arthropathy | Patients requiring biological therapy due to ongoing inflammation (requiring anti-Tumour Necrosis Factor therapy) - i.e. standard of care - escalation in therapy Receives: Other: National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines) | |
| Inflammatory Bowel Disease | Patients with Crohns or Ulcerative Colitis with ongoing inflammation (requiring anti-Tumour Necrosis Factor therapy) - i.e. standard of care - escalation in therapy Receives: Other: National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines) | |
| Healthy volunteers (n=20) | Healthy volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sarcopenia (Muscle Area) using Magnetic Resonance Imaging
Vastus lateralis and rectus femoris muscle axial cross sectional assessment will be measured at 50% of femur length
Measured: 6 months
Sarcopenia (Muscle Area) using ultrasound
Vastus lateralis and rectus femoris muscle axial cross sectional assessment will be measured at 50% of femur length.
Measured: 6 months
Secondary outcomes (4)
Quality of Life questionnaire
Short Form-36 health-related Quality of Life questionnaire (Quality Metric Health Outcomes Solutions, Lincoln, USA)
Measured: 6 month
Muscle biopsy of the Vastus lateralis
Muscle structure using standardised haemotoxylin/eosin and immunohistochemistry
Measured: 6 month
Leg (Quadricep/Hamstring) strength
Leg strength/power by Isokinetic Dynamometry - the patient will be asked to extend the leg as strong as possible and then to flex, for 5 repetitions
Measured: 6 month
Handgrip strength
Both hands using handheld Dynamometer (North Coast Medical, Morgan Hill)
Measured: 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2021
- Study start1 Jan 2019
- Primary completion1 Apr 2020
- Study completion1 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Responsible party
- Principal investigator, Matthew Armstrong, University of Birmingham
- Investigators
- Janet Lord, PhD, Study chair, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04734496
- Sponsor's protocol ID
- RG 18-053
- Other IDs
- 238190
- Status last verified
- Jan 2021
- First submitted
- 18 Jan 2021
- Last updated
- 2 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Williams FR, Quinlan JI, Dhaliwal A, Nicholson T, Breen L, Greig C, Elsharkawy AM, Lord JM, Rowlands AV, Armstrong MJ. Physical Activity and Frailty in patients with Advanced Chronic Liver Disease: A prospective study. JHEP Rep. 2026 Oct 16:102072. doi: 10.1016/j.jhepr.2026.102072. Online ahead of print.
PubMed 42887647Nicholson T, Allen SL, Quinlan JI, Dhaliwal A, Macleod M, Price J, Hazeldine J, Sagmeister MS, Ditchfield C, McGee KC, Williams FR, Elsharkawy AM, Armstrong MJ, Greig CA, Lord JM, Breen L, Jones SW. Systemic Drivers and Molecular Mechanisms of Sarcopenia in Aetiology-Specific End-Stage Liver Disease. J Cachexia Sarcopenia Muscle. 2026 Jun;17(3):e70294. doi: 10.1002/jcsm.70294.
PubMed 42035707Quinlan JI, Nicholson T, Bell C, Dhaliwal A, Williams FR, Allen SL, Choudhary S, Rowlands AV, Elsharkawy AM, Armstrong MJ, Greig CA, Lord JM, Jones SW, Breen L. Increased quadriceps intermuscular adipose tissue in chronic liver disease is associated with an altered muscle transcriptome compared with healthy age matched controls. Geroscience. 2025 Nov 14. doi: 10.1007/s11357-025-01982-2. Online ahead of print.
PubMed 41239110Dhaliwal A, Williams FR, Quinlan JI, Allen SL, Greig C, Filer A, Raza K, Ghosh S, Lavery GG, Newsome PN, Choudhary S, Breen L, Armstrong MJ, Elsharkawy AM, Lord JM. Evaluation of the mechanisms of sarcopenia in chronic inflammatory disease: protocol for a prospective cohort study. Skelet Muscle. 2021 Dec 11;11(1):27. doi: 10.1186/s13395-021-00282-5.
PubMed 34895316
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Mechanisms of Sarcopenia in Chronic Inflammatory Disease (Chronic Liver Disease, Inflammatory Bowel Disease and Inflammatory Arthritis) Pre and Post Standard of Care Intervention; an Observational Study
- ClinicalTrials.gov ID
- NCT04734496
- Acronym / sponsor ID
- RG 18-053
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 1 Apr 2020 (actual)
- Study completion
- 1 Sep 2021 (estimated)
- First posted
- 2 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective, observational study to assess sarcopenia across three chronic inflammatory diseases: chronic liver disease, Inflammatory Bowel Disease, Rheumatoid Arthritis both before and after therapeutic intervention (standard of care treatment i.e. nutrition/exercise; biologic for IBD etc).
Detailed description
Introduction: Several chronic inflammatory diseases co-exist with and accelerate sarcopenia (reduction in muscle strength, quantity and quality) and negatively impact on both morbidity and mortality. There is limited research on the extent of sarcopenia in such conditions, how to accurately assess it and whether there are generic or disease specific mechanisms driving sarcopenia.
Methods: This prospective cohort study is unique; it provides a multi-modal approach to assess sarcopenia across three chronic inflammatory diseases: chronic liver disease, Inflammatory Bowel Disease, Rheumatoid Arthritis both before and after therapeutic intervention. A total of 170 patients will be recruited (50 with Chronic liver disease, 20 with non-cirrhotic nonalcoholic fatty liver disease, 50 with Inflammatory Bowel Disease and 50 with Rheumatoid Arthritis) and including a comparison cohort of n=20 age-sex matched healthy individuals.
Participants will undergo 4 assessments at defined time points; weeks 0, 2, 12 and 24, with blood tests to assess endocrine and inflammatory status; anthropometric (hand grip strength; mid-arm muscle circumference; triceps skinfold thickness); functional testing (short physical performance battery and isokinetic dynamometry); imaging ( ultrasound and Magnetic Resonance Imaging of the quadriceps), and vastus lateralis muscle biopsy. Physical activity and sleep will be monitored using actigraphy, and quality of life via questionnaires. Food diaries for nutritional intake analysis will be sampled between 0-2, 12 and 24 weeks. Stool and urine samples will be sampled for future microbiome and metabolomics analysis, respectively.
This study will identify mechanisms across the groups and within each cohort, to further target interventions to reduce sarcopenia in the future. This is the first study to use a multi modal assessment to characterise sarcopenia in chronic disease. The multi-modal assessment includes serological, anatomical, functional and histological analyses to evaluate the deep phenotyping of these patients. The observational study of small sample sizes will allow potential future targets for intervention.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Chronic Liver Disease | – | Other: National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines)Patients with end-stage liver disease. Standard of care treatment will be nutrition and exercise as per European Association Study of Liver nutrition guidelines. |
| Rheumatoid Arthritis/Psoriatic arthropathy | – | Other: National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines)Patients requiring biological therapy due to ongoing inflammation (requiring anti-Tumour Necrosis Factor therapy) - i.e. standard of care - escalation in therapy |
| Inflammatory Bowel Disease | – | Other: National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines)Patients with Crohns or Ulcerative Colitis with ongoing inflammation (requiring anti-Tumour Necrosis Factor therapy) - i.e. standard of care - escalation in therapy |
| Healthy volunteers (n=20) | – | –Healthy volunteers |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Chronic liver disease patients will be selected from those who undergo assessment for liver transplantation . A Non-alcoholic fatty liver disease (NAFLD) subset will be screened and recruited from the NAFLD clinic. For Inflammatory bowel disease and Rheumatoid Arthritis, all patients commencing a new biologic treatment (via biologic clinic screening or biologic registry screening) will be screened prior to therapy commencement.
Key inclusion criteria (13 listed)
- A formal confirmed diagnosis of their underlying chronic inflammatory condition:
- Some of the Chronic liver disease cohort will have had a liver biopsy, serological and radiological confirmation will be sufficient.
- Adults aged ≥ 18 years
- Able to confirm written consent to the study
- Biologic therapy naïve on recruitment or commencing a new biologic if in the IBD or RA cohort Pre-existing or current use of immunosuppressant agents or Disease Modifying Antirheumatic Drugs (DMARDs) are acceptable in all cohorts.
Key exclusion criteria (16 listed)
- Refusal or lack capacity to give informed consent.
- Currently enrolled in an interventional trial with active treatment for their chronic disease condition.
- Previously undergone LT or biliary intervention in the Chronic liver disease cohort.
- Underlying or active cancer.
- Biliary intervention if Chronic liver disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines)National Healthcare System Standard of care for each disease type (National Institute for Health and Care Excellence guidelines) | Other | Chronic Liver Disease, Inflammatory Bowel Disease, Rheumatoid Arthritis/Psoriatic arthropathy |
Primary outcome
Sarcopenia (Muscle Area) using Magnetic Resonance Imaging
Time frame: 6 months
Vastus lateralis and rectus femoris muscle axial cross sectional assessment will be measured at 50% of femur length
Sarcopenia (Muscle Area) using ultrasound
Time frame: 6 months
Vastus lateralis and rectus femoris muscle axial cross sectional assessment will be measured at 50% of femur length.
4 secondary outcomes
Quality of Life questionnaire
Time frame: 6 month
Muscle biopsy of the Vastus lateralis
Time frame: 6 month
Leg (Quadricep/Hamstring) strength
Time frame: 6 month
Handgrip strength
Time frame: 6 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2021.
- Derived from this study: PubMed 42887647Williams FR, Quinlan JI, Dhaliwal A, Nicholson T, Breen L, Greig C, Elsharkawy AM, Lord JM, Rowlands AV, Armstrong MJ. Physical Activity and Frailty in patients with Advanced Chronic Liver Disease: A prospective study. JHEP Rep. 2026 Oct 16:102072. doi: 10.1016/j.jhepr.2026.102072. Online ahead of print.
- Derived from this study: PubMed 42035707Nicholson T, Allen SL, Quinlan JI, Dhaliwal A, Macleod M, Price J, Hazeldine J, Sagmeister MS, Ditchfield C, McGee KC, Williams FR, Elsharkawy AM, Armstrong MJ, Greig CA, Lord JM, Breen L, Jones SW. Systemic Drivers and Molecular Mechanisms of Sarcopenia in Aetiology-Specific End-Stage Liver Disease. J Cachexia Sarcopenia Muscle. 2026 Jun;17(3):e70294. doi: 10.1002/jcsm.70294.
- Derived from this study: PubMed 41239110Quinlan JI, Nicholson T, Bell C, Dhaliwal A, Williams FR, Allen SL, Choudhary S, Rowlands AV, Elsharkawy AM, Armstrong MJ, Greig CA, Lord JM, Jones SW, Breen L. Increased quadriceps intermuscular adipose tissue in chronic liver disease is associated with an altered muscle transcriptome compared with healthy age matched controls. Geroscience. 2025 Nov 14. doi: 10.1007/s11357-025-01982-2. Online ahead of print.
- Derived from this study: PubMed 34895316Dhaliwal A, Williams FR, Quinlan JI, Allen SL, Greig C, Filer A, Raza K, Ghosh S, Lavery GG, Newsome PN, Choudhary S, Breen L, Armstrong MJ, Elsharkawy AM, Lord JM. Evaluation of the mechanisms of sarcopenia in chronic inflammatory disease: protocol for a prospective cohort study. Skelet Muscle. 2021 Dec 11;11(1):27. doi: 10.1186/s13395-021-00282-5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janet Lord, PhD study chair
University of Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Liver Disease and Rheumatoid Arthritis, run by University of Birmingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sarcopenia (Muscle Area) using Magnetic Resonance Imaging (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04734496, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2021.