Current Clinical Trials

This section will be populated with more information about our current studies in the next few weeks.  You many find a summary outline of some of our open studies below.  If you have any questions, please email us on: arthritisresearch@glasgow.ac.uk.

Biomarker Association in Skin and Synovium in Psoriatic Arthritis Study (BASSPA)

Study Summary (including aims, timelines and funder):

Psoriatic arthritis (PsA) is an inflammatory arthritis which affects up to 30% of patients with psoriasis. The relationship between the joint disease (inflammatory arthritis) and skin disease (psoriasis) is not completely understood but the immune system is involved in both aspects of the disease. Currently, there is no way of determining which treatment will be most beneficial in individual patients and treatment decisions in clinic remain based largely on "trial-and error" with no good biomarkers to support these decisions.  

With the BASSPA study, we want to better understand inflammation in arthritis and psoriasis. To do this, westudy the immune cells and proteins/biomarkers in blood and urine samples, together with detailed clinical assessments. In addition, we perform biopsies of the skin and joint in a sub-group of people with PsA, so that we can study these cells and proteins in the skin and joints too. 

A better understanding of inflammation in arthritis and psoriasis and how people respond to treatments can help researchers predict how people will respond to different treatments. 

 Primary research objective

  • To find disease specific biomarkers and cell types in blood, skin and the lining of joints in patients with PsA.

Secondary research objectives

  • To correlate these biomarkers and cell populations with clinical activity.
  • To assess the effect of PsA treatments on blood, skin and synovial biomarkers and cell populations.

This prospective, observational study will recruit 30 patients with PsA (and 5 controls with rheumatoid arthritis, RA) who are due to start a disease modifying drug (DMARD) or biologic as part of their standard clinical care. It will measure immune cells and proteins/biomarkers before and during treatment. Participants are followed up for 1 year. 

The first participant was recruited in March 2018 and it is expected that recruitment will conclude at the end of June 2019. 

The study is funded by Boehringer Ingelheim.

Who can participate? (Inclusion/exclusion criteria)

Patients with PsA (30) and RA (5) who have active disease and are due to start or change a disease modifying drug (DMARD) or biologic as part of their standard clinical care.

 What does the study involve?

The study involves 5 visits in a 12-month period. 

At all visits, a clinical assessment is performed, questionnaires completed, and blood tests taken. Urine samples are collected at 3 visits. 

At the first visit, participants also have an ultrasound performed and X-rays of hands and feet. 

A sub-group of 10 patients with PsA will undergo skin and joint biopsies at the first visit. Skin +/- joint biopsies are repeated after 3 months. 

Are there any benefits or risks associated with taking part in this study?

This is an observational study with no direct benefit for the participants. 

As with any invasive procedures, there are risks associated with skin and synovial biopsies. These are discussed in detail with participants who consider participation in the sub-study.  

 


BIOlogical-Factors that Limit sustAined Remission in rhEumatoid arthritis (BIO-FLARE)

Study Summary (including aims, timelines and funder):

Rheumatoid arthritis is a relapsing and remitting autoimmune disease. The challenge that we will address is why immune-mediated inflammatory diseases (IMIDs) remit and relapse. Whilst a considerable amount is understood about factors which may contribute to development of RA and about disease mechanisms, nothing is known of the factors that trigger disease relapses (flares), converting the disease from an inactive to an active state. The underpinning mechanism(s) of flare have been difficult to study because they occur unpredictably. By studying patients who flare, we will attempt to capture signals that may determine which patients are most likely to flare, as well as understanding the biology behind the phenomenon of flare itself. This may eventually lead to future work on treatable targets in disease management.   Funder: Medical Research Council

What does the study involve?

In this study, we will recruit patients in remission from RA on traditional disease modifying therapies (DMARDs), namely methotrexate, sulfasalazine, and/or hydroxychloroquine. These patients will then discontinue their DMARDs and be closely followed-up by the research team. Previous research suggests 50% will experience flare, while the remainder will remain in remission. They will have regular assessment of their disease activity (physical examination and questionnaires), along with clinical and research blood samples taken. Urine samples will be taken at each visit. If a patient in the study experiences a flare, they will have an ultrasound-guided synovial biopsy taken under local anaesthetic. Samples of blood, urine and synovium (joint lining) will be analysed for gene expression, synovial cell subtypes, molecular pathways, immune cell profiles, and antibody status. 

After 6 months, if a patient does not experience a flare, they will be referred back to their usual rheumatologist and may be able to remain off of DMARDs. If a patient experiences flare at any time, they will receive steroid treatment and be referred back to their usual rheumatologist to restart their DMARDs. 

Are there any benefits or risks associated with taking part in this study?

The main perceived ethical issue will be withdrawal of DMARD therapy from patients in clinical remission, although this might in fact be considered potentially beneficial for participants. DMARDs are not without adverse (side) effects, ranging from common symptoms such as nausea to less common but more serious side-effects such as bone marrow suppression, infection, and liver or lung injury. The risk of some of these problems is dependent on cumulative lifetime dosage. With this in mind, regular blood test monitoring is standard care while patients are taking these medications. These add a further inconvenience to patients, as well as additional costs to healthcare providers. Our qualitative data (submitted for publication) and feedback from patients’ engagement groups show that many patients view DMARDs as a significant burden on quality of life, and would value the opportunity of DMARD discontinuation. Minimisation of DMARDs in the setting of RA remission is supported by current RA management guidelines issued by the National Institute of Health and Care Excellence, as well as the European League Against Rheumatism 

Synovial biopsy represents a further potential ethical issue. Minimally invasive ultrasound-guided synovial biopsy has been practiced since 2007. This procedure was specifically developed to minimise discomfort and inconvenience for patients with newly developed arthritis and has been shown to be safe and well tolerated by patients, as well as generating high quality samples, including from patients in clinical remission. The three main units using this technique internationally (including Birmingham) have completed more than 1000 biopsies with no major adverse events. Audit of biopsies in Birmingham has demonstrated that >90% of patients experience nothing more than mild to moderate discomfort during the procedure, with >80% of patients likely to consent to a second biopsy. Biopsy of patients in remission is optional in BIO-FLARE, and would only be considered where a sufficient synovial biopsy target is identified by ultrasound. 

Offsetting these above potential issues is the fact that up to 50% of patients are likely to remain off of DMARDs for prolonged periods of time, potentially for several years. Furthermore, participants will be contributing to an important piece of research that addresses a clinically important question. 

 

Study contacts for further information

Dr Seán Kerrigan, Glasgow Clinical Research Facility 0141 211 6800 or email: arthritisresearch@glasgow.ac.uk


Characterising the Centralised Pain Phenotype in Chronic Rheumatic Disease (CENTAUR)

Study Summary (including aims, timelines and funder):

Psoriatic arthritis (PsA) is an inflammatory arthritis which affects both joint (inflammatory arthritis) and skin (psoriasis). In recent decades, the introduction of extraordinarily effective treatments have transformed patient outcomes. However, a considerable number of patients continue to experience persistent chronic pain, despite apparent disease remission. This may be explained by the existence of alternative sources of pain. We believe that pain is not only caused by joint inflammation, but also the nervous system (brain and nerves).,We call this the  centralised component of pain.

Several studies have explored the central component of pain in different rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and fibromyalgia. Currently, there are no investigations exploring this type of pain in PsA. Even though there are treatments available to manage centralised pain, there are not the clinical tools or biomarkers to help distinguish the different sources of pain.  These are vital to improve the management and ultimately the quality of life of patients.

The CENTAUR study aims to characterise centralised pain in PsA patients. To do this, we are going to use comprehensive measurement including objective pain sensory tests and Magnetic Resonance Imaging (MRI) brain scans alongside  questionnaires and diseases activity measurements.

The primary research objective is to investigate the neurobiology of PsA patients, especially in patients with high centralised pain.

The secondary research objective is to develop a simple questionnaire which may be used routinely in clinic to characterise the type of pain reported by the patients and finally to inform precise treatment decisions.

This observational study will recruit 50 patients with PsA who are due to start a new disease modifying drug (DMARD) as part of standard clinical care. Clinical data, objective and subjective pain assessments will be collected at baseline and selected measures will be repeated at 3 and 6 months.

The recruitment is expected to start in April 2019 and it will conclude at the end of July 2021. 

The study is funded by Versus Arthritis (previously named Arthritis Research UK).

Who can participate? (Inclusion/exclusion criteria)

Patients with a diagnosis of PsA who have evidence of active disease active disease and are due to start a new disease modifying drug (DMARD) as part of their standard clinical care. 

Patients with any contraindication to MRI or with peripheral neuropathy can be not be enrolled in the study.

What does the study involve? 

Eligible patients who agree to participate will attend the clinical research facility at baseline, 3 and 6 months. 

At the baseline visit, the patient will undertake a clinical assessment, blood samples, questionnaire, quantitative sensory testing (QST), and a MRI brain scan. The clinical assessment and blood samples will reflect standard care. The questionnaire will assess symptoms and risk factors of pain. The QST is a well standardised set of tests suitable to measure sensitivity of pressure and visual stimuli. The MRI scan will be recording structural and functional information of the participant brain with particular focus on that areas known to be involved in pain. 

At the 3 and 6 months visits, only the clinical assessments, blood sampling and questionnaire assessments will be performed.

Are there any benefits or risks associated with taking part in this study?

A benefit from taking part in this study may not be directly achieved. However, the future results will help patients with PsA and rheumatic diseases in general. Moreover, joining a clinical trial may reveal a new medical condition that will be properly follow up and treated.

MRI is a very well-known imaging test which is overall safe. It does not involve the use of any radiation. Patients with contraindications to the MRI scan, such as metal implants or claustrophobia, will be appropriately excluded. QST is a set of different procedures commonly employed in research which have been planned following safety standards. However, a temporary discomfort may arise in the areas tested.  

Study contacts for further information 

Dr Flavia Sunzini (Clinical Research Fellow):  Flavia.Sunzini@glasgow.ac.uk

Dr Neil Basu (Chief Investigator): Neil.Basu@glasgow.ac.uk

 

 


Inhibition of Co-Stimulation in Rheumatoid Arthritis (ICoSRA)

Study Summary (including aims, timelines and funder):

ICoSRA is an international clinical study which utilises laboratory based, genetic patient screening and analysis to unravel immune responses in people with rheumatoid arthritis. The study aims to identify predictive markers of response to rheumatoid arthritis treatment regimes.  It also will provide new information about why the disease occurs and thereby point to future possible approaches to cure.

Rheumatoid arthritis (RA) is a chronic inflammatory immune-mediated arthritis which leads to pain, swelling and destruction of joints. RA affects more than 500,000 subjects in the UK and incurs significant health and economic cost. Most patients require potent immune suppressing drugs such as methotrexate, which help reduce pain and stiffness, and protect the joints against damage. However, many patients do not respond or are unable to tolerate methotrexate. In these patients, biologic drugs such as abatacept are used to try to control the arthritis.  

Abatacept is an injectable medicine designed to target and inhibit a specific molecule involved in “costimulation” of the inflammatory signal (that switches on white blood cells) that is thought to be important in RA. While abatacept has been shown to be effective in trials and clinical practice, the exact mechanism of action of abatacept in RA has not been fully elucidated. Understanding these actions is likely to inform both the use of abatacept in RA and lead to increased understanding of inflammation in humans with implications for further therapies. This six month prospective open-label study, therefore, aims to investigate the effects of inhibiting co-stimulation on a variety of important inflammatory cell types and processes in humans with RA.

This study is funded by Bristol-Myers Squibb.

Who can participate? (Inclusion/exclusion criteria)

25 participants with RA who have bad prognostic genetic markers (ACPA and HLA-DR4) and who were scheduled to receive subcutaneous abatacept as part of their standard clinical treatment will be recruited. 

 What does the study involve?

Consenting participants will be followed for a total of 24 weeks during which time they will have additional venous blood and urine samples taken to investigate the effects of abatacept on their immune cells and system. The primary endpoint of the study is the characterisation of the immune response following costimulatory modulation in RA patients at 12 weeks. Secondary endpoints include change in immunological response and its association with clinical outcome measures up to 24 weeks.

Are there any benefits or risks associated with taking part in this study?

We cannot predict the outcome of the study, but there is the possibility that there will be benefits to those subjects receiving the active drug, including reduction of joint symptoms and effects on the disease process that could delay or even prevent the onset of arthritis or RA.  Another important benefit to participating is that you will be monitored very closely by the clinical research team. You will have a dedicated research nurse who you will be able to contact directly with any questions or concerns relating to your care or participation throughout the study.  


Immune Metabolic Associations in Psoriatic Arthritis (IMAPA)

Study Summary (including aims, timelines and funder):

Psoriatic arthritis (PsA) and psoriasis are characterised by immune, metabolic, and vascular dysfunction. There is an increase in Major Adverse Cardiovascular Events in PsA and psoriasis not explained by conventional cardiovascular risk factors. Further, obesity is strongly associated with psoriasis and PsA. Dietary interventions leading to weight loss are associated with improvement in disease activity. Phosphodiesterase 4 (PDE4) inhibition with apremilast, licensed for treatment of PsA and psoriasis, has been noted to be associated with weight loss. PDE4 may help explain the link between immune and cardiometabolic dysfunction characterising PsA and psoriasis, with pathogenic and therapeutic implications.

This study aims to use apremilast as a clinical molecular probe to evaluate the effects of PDE4 inhibition on metabolic, vascular, and immune status in patients with PsA and psoriasis. 

Measurement of metabolic, immunological and vascular outcomes in 60 patients with PsA and/or psoriasis receiving apremilast as part of their standard clinical care will be taken. A subgroup of participants with PsA will also undergo more in-depth investigations including MRI of abdominal fat distribution, subcutaneous adipose tissue biopsy, vascular endothelial function, and more detailed immunophenotyping. Participants will be recruited from rheumatology and dermatology clinics in NHS Greater Glasgow and Clyde (primary site), as well as from NHS Lanarkshire and NHS Highland.

This is an investigator-initiated study funded by Celgene, manufacturer of apremilast, with sub-study funding from the BHF Centre of Research Excellence. Celgene do not supply or fund apremilast, this is prescribed as part of standard clinical care.

Who can participate? 

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Have either a diagnosis of: PsA fulfilling the CASPAR criteria or Chronic plaque psoriasis (confirmed by dermatologist) 
  3. Eligible for apremilast therapy in line with the licence and SMC approval
  4. Able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria:

  1. History of or current autoimmune rheumatic disease other than PsA or psoriasis
  2. Severe renal disease (eGFR ≤30ml/min)
  3. Liver disease with ALT/AST >4 times ULN
  4. Haemoglobin ≤9 g/dl
  5. Inflammatory bowel disease or coeliac disease
  6. Patients with any cancer currently receiving chemo- or radiotherapy
  7. Severe depression and/or history of suicidal ideation or attempts.
  8. Currently receiving other leflunomide or biologics
  9. Current oral steroids or IM steroids within 6 weeks of baseline.
  10. Clinically meaningful weight loss of >3kg, current or planned use of weight loss medication e.g. orlistat, or severe calorie restriction within the first 3 months of the study
  11. Current insulin therapy for diabetes
  12. Current use of GLP-1 agonists or dipeptidyl peptidase-4 (DPP-IV) inhibitors
  13. Statin therapy started/stopped or dose altered within 3 months of baseline visit
  14. Thyroxine started or dose altered within 6 weeks of baseline
  15. Acitretin within 8 weeks of baseline
  16. Pregnancy or breast feeding
  17. Women planning to become pregnant during the study period
  18. Women of reproductive age or male partners of women of reproductive age unwilling to use effective contraception while taking apremilast & for at least 28 days after last dose of apremilast
  19. Known HIV, hepatitis B and C infection
  20. Patient unable to participate in long term data collection

What does the study involve?

Participants will undergo four assessments: baseline prior to starting apremilast, and at 1 month, 3 months and 6 months of treatment.  At baseline, month 3, and month 6 visits, an oral glucose tolerance test (OGTT) will be performed; at month 1, a single set of fasting blood samples are taken.  In addition, formal assessment of affected joints (66/68 joint count) and skin (PASI) will be undertaken, as well as standard anthropometric measurements and blood pressure at each visit. The participant will be asked to complete a series of questionnaires related to appetite, physical activity, activities of daily living, mood, and gastrointestinal symptoms. A subset of participants will undergo whole body MRI to assess body fat distribution, subcutaneous fat biopsy, vascular function assessment with EndoPAT, and will have blood drawn for more detailed immunophenotyping. 

Are there any benefits or risks associated with taking part in this study?

Every participant will receive apremilast and will therefore receive active medication. The decision to initiate apremilast will be made by the patient’s usual specialist (rheumatologist or dermatologist) as part of their standard clinical care and independently of the study. Decisions to stop or continue with apremilast will be based on standard clinical care. Therefore, participants in the study will receive exactly the same treatments as those not participating, so will have no different medication exposure or risk than standard care.  Please consult your rheumatologist or dermatologist and/ or the product literature for potential side effects of apremilast.

All study components are generally well-tolerated.  Participants in the sub-study who undergo subcutaneous fat biopsy may experience some bruising after the procedure, this should settle within a week or two.  There is a small risk of local infection of the skin, bleeding, or pain around the biopsy site, but these are uncommon and short-lived.  Individuals undergoing MRI are asked to complete a safety questionnaire prior to this to ensure they are suitable.

Study contacts for further information

Dr Lyn D Ferguson (Clinical Research Fellow): lyn.ferguson@glasgow.ac.uk

Dr Stefan Siebert (Chief Investigator): Stefan.siebert@glasgow.ac.uk


Stratification of Biologic Therapies for RA by Pathobiology (STRAP)

Study Summary (including aims, timelines and funder):

Part of the MATURA consortium led by Queen Mary University London, the Stratification of Biologic Therapies for RA by Pathobiology (STRAP) study is investigating 3 biological therapies; Rituximab, Tocilizumab and Etanercept. The study started in November 2015 and is investigating whether the most effective drug for a specific patient can be identified by examining the joint tissue from synovial biopsies. 

The aim of this study is to investigate whether the most effective choice of biologic medicine for people with RA may be guided by examining the joint tissue (synovial tissue) and, in particular, whether different levels of immune cells (called B cells) within the joint can predict response to treatment.

The ultimate aim is to provide a tailored approach to treatment decisions for people with RA, in order to maximize their potential response to biologic medicines. 

Who can participate? (Inclusion/exclusion criteria)

Patients with active (DAS28 ≥ 5.1) who have failed at least 2 Disease Modifying Anti-Rheumatic Drugs (or DMARDs; including methotrexate, sulfasalazine and hydroxychloroquine), who have not previously received treatment with biologic drugs.

Glasgow started recruitment in October 2016.  11 patients have been recruited in Glasgow to date.  

What does the study involve?

With your permission, you will first attend a screening visit (approximately 1 hour), which will assess your eligibility for the study in more detail, which will include:

  • Full medical history including medical conditions and surgical procedures, allergies, medication list, etc 
  • Completing questionnaires
  • A full physical examination 
  • Thorough examination of all your joints
  • Chest X-ray
  • Electrocardiography (ECG)
  • Routine blood test
  • Vital signs including blood pressure, pulse rate, 
  • Urine pregnancy test if you are a woman of child-bearing age

If the tests show that you are suitable for the study and you agree to take part, you will need to agree to have a biopsy of one of your inflamed joints (usually the knee or wrist joint). This will be done by a doctor and will involve removal of small tissue samples from the lining of the joint (synovial tissue). Following this, you will be assigned to one of three treatments (etanercept, rituximab or tocilizumab), which you will first receive on the ‘baseline’ visit.  Subsequently, you will attend follow-up visits every 4 weeks for a total of 24 weeks. During these visits, you will be asked to complete questionnaires and have some tests carried out. 

 These tests may include:

  • Blood tests
  • Additional biopsies (optional)
  • X-rays of your hands and feet

Are there any benefits or risks associated with taking part in this study?

A perceived risk to the patient may be that of undergoing synovial biopsy.  Minimally invasive ultrasound-guided synovial biopsy has been practiced since 2007. This procedure was specifically developed to minimise discomfort and inconvenience for patients with newly developed arthritis and has been shown to be safe and well tolerated by patients, as well as generating high quality samples, including from patients in clinical remission. The three main units using this technique internationally (including Birmingham) have completed more than 1000 biopsies with no major adverse events. Audit of biopsies in Birmingham has demonstrated that >90% of patients experience nothing more than mild to moderate discomfort during the procedure, with >80% of patients likely to consent to a second biopsy.

We cannot predict the outcome of the study or participants individual responses to treatment.  The three therapies participants may receive in the study are routinely used in patients with RA by clinicians as usual clinical care.  They have all proven effective for the management of RA, but determining which drug is best for which patient is ultimately what the trial aims to discover; hence, responses may vary within the study as they would in standard care.  An important benefit to participating is that patients will be monitored very closely by the clinical research team. They will have a dedicated research nurse who you will be able to contact directly with any questions or concerns relating to your care or participation throughout the study.  

 Additionally, although not of direct benefit, participation in this study will provide important new information about the feasibility and acceptability of approaches to preventing RA.

 

Study contacts for further information

Dr Seán Kerrigan, Glasgow Clinical Research Facility 0141 211 6800 or email: arthritisresearch@glasgow.ac.uk