Immune Metabolic Associations in Psoriatic Arthritis (IMAPA)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03399708 |
|
Recruitment Status :
Completed
First Posted : January 16, 2018
Last Update Posted : November 25, 2019
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment |
|---|---|
| Psoriasis Psoriatic Arthritis | Drug: Apremilast 30mg |
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).
| 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 |
- 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.
- Changes in cardiometabolic profile [ Time Frame: 3 months ]To characterise dynamic changes in cardiometabolic profile with formal assessment at 3 months.
- Lipids [ Time Frame: 6 months ]Change in lipid profile
- NMR metabolomic profile [ Time Frame: 6 months ]Change in NMR metabolomic profile
- Blood pressure [ Time Frame: 6 months ]Change in blood pressure
- endothelial function [ Time Frame: 3 months ]change in endothelial function
- MRI imaging [ Time Frame: 3 months ]change in visceral, subcutaneous, liver, and pancreatic fat as assessed by MRI imaging
- GLP-1 levels [ Time Frame: 6 months ]Change in fasting & post-prandial GLP-1 levels
- adipose tissue [ Time Frame: 3 months ]Change in adipose tissue composition
- immune profile [ Time Frame: 6 months ]Change circulating cytokines
Biospecimen Retention: Samples Without DNA
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Probability Sample |
Inclusion Criteria:
- Age ≥ 18 years
- Have either a diagnosis of PsA (n=40) fulfilling the CASPAR criteria or Chronic plaque psoriasis (confirmed by dermatologist) (n=20)
- Eligible for apremilast therapy in line with the licence and SMC approval
- Able and willing to give written informed consent and comply with the requirements of the study protocol.
Exclusion Criteria:
- History of or current autoimmune rheumatic disease other than PsA or psoriasis
- Severe renal disease (eGFR ≤30ml/min)
- Liver disease with ALT/AST >4 times ULN
- Haemoglobin ≤9 g/dl
- Inflammatory bowel disease or coeliac disease
- Patients with any cancer currently receiving chemo- or radiotherapy
- Severe depression and/or history of suicidal ideation or attempts.
- Currently receiving other leflunomide or biologics
- Current oral steroids or IM steroids within 6 weeks of baseline.
- 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
- Current insulin therapy for diabetes
- Current use of GLP-1 agonists or dipeptidyl peptidase-4 (DPP-IV) inhibitors
- Statin therapy started/stopped or dose altered within 3 months of baseline visit
- Thyroxine started or dose altered within 6 weeks of baseline
- Acitretin within 8 weeks of baseline
- Pregnancy or breast feeding
- Women planning to become pregnant during the study period
- 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
- Known HIV, hepatitis B and C infection
- Patient unable to participate in long term data collection
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
| United Kingdom | |
| Glasgow Royal Infirmary | |
| Glasgow, Scotland, United Kingdom, G31 2ER | |
| Principal Investigator: | Stefan Siebert, MBChB PhD | Glasgow University and NHS GGC |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
|
apremilast PDE4 inhibition cardiometabolic immune profile |
|
Arthritis Arthritis, Psoriatic Psoriasis Joint Diseases Musculoskeletal Diseases Skin Diseases, Papulosquamous Skin Diseases Spondylarthropathies Spondylarthritis Spondylitis Spinal Diseases Bone Diseases Apremilast |
Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics 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 |