Sarcopenia and Rheumatoid Arthritis Musculoskeletal Diseases Sarcopenia and Rheumatoid Arthritis
Conditions
Interventions
Current intervention as of 05/02/2021:
Observational single-arm study of skeletal muscle metabolism in patients with rheumatoid arthritis receiving tofacitinib
Potential participants will be identifi
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 2010 ACR/ EULAR classification criteria for a diagnosis of rheumatoid arthritis 2. At least 6 months disease duration 3. Inadequate response to intensive therapy with synthetic disease-modifying anti-rheumatic drugs (DMARDs) alone, or inadequate response to at least one biologic DMARD, thereby qualifying for treatment with tofacitinib according to local guidelines. 4. Aged >18 years 5. Willing and able to provide written informed consent. 6. ACR Functional Class I-III 7. Willing to undergo muscle biopsy on 2 occasions. 8. Willing to undergo MRI and MRS and Dexa scan on 3 occasions 9. Active systemic disease, as exemplified by a C-reactive protein of at least 10 mg/l
Exclusion criteria
Exclusion criteria: 1. Serum creatinine that is above the upper limit of normal at baseline. 2. Patients receiving glucocorticoids 3. Patients will be excluded if they have any contraindications to tofacitinib which include: 3.1 Pregnancy and lactation 3.2 Women of childbearing potential (WOCP) who are not prepared to use effective contraception during treatment with tofacitinib and for at least 4 weeks after the last dose. 3.3 Severe hepatic impairment (Child Pugh C) 3.4 Active TB, serious infections such as sepsis or opportunistic infections as detailed in the SmPC 3.5 Chronic infections (HIV, hepatitis B, hepatitis C) 4. Participants will be excluded if they have any contraindications to muscle biopsies. These include: 4.1 Participants on anticoagulant therapy. These include vitamin K antagonists, thrombin inhibitors, and heparin and low molecular weight heparin preparations. 4.2 Participants on antiplatelet therapy. *Participants on aspirin for primary prevention will be included in this study. However, aspirin will be held for 7 days prior to the muscle biopsies and recommenced 48 hours after. 4.3 Participants who are known to have bleeding disorders. These include, but are not limited to, haemophilia, Factor II, V, VII, X, or XII deficiencies and Von Willebrand's disease 4.4 Previous reactions to local anesthetics 4.5 Platelets count 190 kg 5.7 Claustrophobia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in muscle bulk measured by accelerated MRI of lower limbs | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 05/02/2021: 1. Muscle function/strength at baseline, and 1 and 6 months after commencing tofacitinib assessed by hand grip and timed raise from chair 2. Muscle biochemistry assessed by magnetic resonance spectroscopy of skeletal muscle: content of ATP, phosphocreatine and inorganic phosphate at baseline, 1 month and 6 months, assessed by magnetic resonance spectroscopy. 3. Serum biochemistry: Serum creatinine, serum creatine phosphokinase, serum aspartate transaminase, serum aldolase, serum myoglobin and serum cystatin C at baseline, 1 month and 6 months. 4. Relationship between changes in serum biochemistry (serum creatinine, serum creatine phosphokinase) to biochemical, structural, functional and histological/molecular changes in muscle 5. Relationship between changes noted in muscle and reduction in systemic inflammation 6. Body composition using DEXA at baseline, 1 month and 6 months Previous secondary outcome measures 1. Muscle function/strength at baseline, and 1 and 6 months after commencing Tofacitinib assessed by hand grip and timed- raised from chair 2. Muscle biochemistry assessed by magnetic resonance spectroscopy of skeletal muscle: content of ATP, phosphocreatine and inorganic phosphate at baseline, 1 month and 6 months, assessed by magnetic resonance spectroscopy. 3. Serum biochemistry: Serum creatinine, serum creatine phosphokinase, serum aspartate transaminase, serum Aldolase, serum Myoglobin and serum Cystatin C at baseline, 1 month and 6 months. 4. Relationship between changes in serum biochemistry (serum creatinine, serum creatine phosphokinase) to biochemical, structural, functional and histological/molecular changes in muscle 5. Relationship between changes noted in muscle and reduction in systemic inflammation | — |
Countries
England, United Kingdom
Contacts
Public ContactJosh Bennett
Outcome results
None listed