Evaluation of the Mechanisms of Sarcopenia in Chronic Inflammatory Disease: Protocol for a Prospective Cohort Study

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04734496
• Other study ID #: RG 18-053
• Secondary ID: 238190
• Status: Active, not recruiting
• Start date: January 1, 2019
• Est. completion date: September 1, 2021

Study information

• Verified date: January 2021
• Source: University of Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 170
• Est. completion date: September 1, 2021
• Est. primary completion date: April 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. A formal confirmed diagnosis of their underlying chronic inflammatory condition:

1. 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.

2. RA cohort, clinical, serological and radiological confirmation will be sufficient.

3. Biologic therapy naïve on recruitment or commencing a new biologic if in the IBD or IA cohort.

2. Adults aged = 18 years

3. Able to confirm written consent to the study

4. 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.

5. Meeting ACR (American College of Rheumatology) /EULAR (European League Against Rheumatism) 2010 or ACR 1987 Criteria for rheumatoid arthritis and starting DMARD therapy.

6. Meeting criteria of an inflammatory arthritis as per the American College of Rheumatology

7. Meeting criteria of liver cirrhosis including all Child Pugh scores from A-C as per British Association for the Study of the Liver guidance.

8. Meeting criteria for Inflammatory bowel disease as per the British Society of Gastroenterology guidance.

9. For muscle biopsy sampling (does not preclude patients from participating if they do not meet the below criteria) INR = 1.6 Platelet count > 30

Exclusion Criteria:

1. Refusal or lack capacity to give informed consent.

2. Currently enrolled in an interventional trial with active treatment for their chronic disease condition.

3. Previously undergone LT or biliary intervention in the Chronic liver disease cohort.

4. Underlying or active cancer.

5. Biliary intervention if Chronic liver disease

6. For Muscle biopsies only (able to continue in study):

1. Obvious injury to both thighs.

2. Active bleeding of site, pre-procedure,

3. Abnormal observation parameters.

4. Acute illness.

5. INR > 1.6.

6. Platelet count < 30.

7. Anticoagulation which cannot be paused due to increased risk to pre-existing co-morbidity.

7. For undergoing an Magnetic resonance imaging (MRI)

1. Pacemaker.

2. Metal work inserted that is not MRI compatible or further information cannot be obtained.

Related Conditions & MeSH terms

• Arthritis
• Chronic Liver Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Liver Diseases
• Rheumatoid Arthritis
• Sarcopenia

Intervention

Other:
• 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)

Locations

Country	Name	City	State
United Kingdom	Institute of Inflammation and Ageing (IIA) University of Birmingham Research Laboratories	Birmingham	West Midlands

Sponsors (2)

Lead Sponsor	Collaborator
University of Birmingham	National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	6 months
Primary	Sarcopenia (Muscle Area) using ultrasound	Vastus lateralis and rectus femoris muscle axial cross sectional assessment will be measured at 50% of femur length.	6 months
Secondary	Quality of Life questionnaire	Short Form-36 health-related Quality of Life questionnaire (Quality Metric Health Outcomes Solutions, Lincoln, USA)	6 month
Secondary	Muscle biopsy of the Vastus lateralis	Muscle structure using standardised haemotoxylin/eosin and immunohistochemistry	6 month
Secondary	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	6 month
Secondary	Handgrip strength	Both hands using handheld Dynamometer (North Coast Medical, Morgan Hill)	6 month