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Immune Metabolic Associations in Psoriatic Arthritis (IMAPA)

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ClinicalTrials.gov Identifier: NCT03399708
Recruitment Status : Completed
First Posted : January 16, 2018
Last Update Posted : November 25, 2019
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde

Brief Summary:
To use apremilast in clinical practice as a molecular probe to evaluate the effects of PDE4 inhibition on the cardiometabolic status and immune profile in patients with PsA and psoriasis.

Condition or disease Intervention/treatment
Psoriasis Psoriatic Arthritis Drug: Apremilast 30mg

Detailed Description:

Psoriatic arthritis (PsA) and psoriasis are characterised by immune, metabolic, and vascular dysfunction. There is an increase in Major Adverse Cardiovascular Events in people with PsA and psoriasis not explained by conventional cardiovascular risk factors. Furthermore, obesity in psoriasis is associated with increased risk of developing PsA3. Dietary interventions leading to weight loss >5% are associated with a higher rate of achievement of minimal disease activity in overweight/obese patients with PsA treated with TNF inhibitors. Phosphodiesterase 4 (PDE4) inhibition with apremilast is licensed for the treatment of PsA and psoriasis and has been noted to be associated with weight loss. There is also data from animal models to suggest a role for PDE4 in glucose metabolism. However, the exact mechanisms underlying this are unclear and warrant investigation in humans. PDE4 may help explain the link between the immune and cardiometabolic dysfunction that characterises 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. The hypothesis is that PDE4 inhibition mediates profound and synergistic effects on immune and metabolic pathways in these conditions to improve metabolic status and normalise dysregulated immunity.

Measurement of metabolic, immunological and vascular outcomes in 60 patients (40 with PsA and 20 with psoriasis) receiving apremilast as part of their standard clinical care will be taken. A subgroup of 20 participants with PsA will also undergo more in-depth investigations including MRI of abdominal fat, subcutaneous fat biopsy, measurement of vascular endothelial function using EndoPAT and more detailed deep-immunophenotyping. Patients will be recruited from rheumatology and dermatology clinics in NHS Greater Glasgow and Clyde (primary site) and two other recruiting sites in Scotland via the Scottish Collaborative Arthritis Research network (SCAR).

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Study Type : Observational
Actual Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Immune Metabolic Associations in Psoriatic Arthritis Study
Actual Study Start Date : June 12, 2017
Actual Primary Completion Date : October 12, 2019
Actual Study Completion Date : October 25, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Apremilast

Intervention Details:
  • Drug: Apremilast 30mg
    Apremilast will used in line with its license. This includes the standard dose titration scheme (see section 6) and then the usual maintenance dose of 30 mg twice daily orally.

Primary Outcome Measures :
  1. Changes in cardiometabolic profile [ Time Frame: 3 months ]
    To characterise dynamic changes in cardiometabolic profile with formal assessment at 3 months.

Secondary Outcome Measures :
  1. Lipids [ Time Frame: 6 months ]
    Change in lipid profile

  2. NMR metabolomic profile [ Time Frame: 6 months ]
    Change in NMR metabolomic profile

  3. Blood pressure [ Time Frame: 6 months ]
    Change in blood pressure

  4. endothelial function [ Time Frame: 3 months ]
    change in endothelial function

  5. MRI imaging [ Time Frame: 3 months ]
    change in visceral, subcutaneous, liver, and pancreatic fat as assessed by MRI imaging

  6. GLP-1 levels [ Time Frame: 6 months ]
    Change in fasting & post-prandial GLP-1 levels

  7. adipose tissue [ Time Frame: 3 months ]
    Change in adipose tissue composition

  8. immune profile [ Time Frame: 6 months ]
    Change circulating cytokines

Biospecimen Retention:   Samples Without DNA
Routine blood (FBC, creatinine and/or GFR, LFTs) Acute phase reactants: ESR, CRP Oral Glucose Tolerance test (OGTT) = 0,30,60,90,120min (glucose, insulin) =0, 30, 120 min (GLP-1) Fasting lipids, HbA1c, glucose, insulin, GLP-1 levels Blood samples for NMR metabolomic profiling Circulating cytokines & adipokines

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with PsA and psoriasis.

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Have either a diagnosis of PsA (n=40) fulfilling the CASPAR criteria or Chronic plaque psoriasis (confirmed by dermatologist) (n=20)
  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 meanigful 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03399708

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United Kingdom
Glasgow Royal Infirmary
Glasgow, Scotland, United Kingdom, G31 2ER
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
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Principal Investigator: Stefan Siebert, MBChB PhD Glasgow University and NHS GGC
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Responsible Party: NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier: NCT03399708    
Other Study ID Numbers: GN16RH008
First Posted: January 16, 2018    Key Record Dates
Last Update Posted: November 25, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by NHS Greater Glasgow and Clyde:
PDE4 inhibition
immune profile
Additional relevant MeSH terms:
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Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Skin Diseases, Papulosquamous
Skin Diseases
Spinal Diseases
Bone Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Phosphodiesterase 4 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action