Elucidating Shared Mechanisms Contributing to NAFLD and PsA Disease Severity With Guselkumab Therapy

Study Purpose

While many studies examine Nonalcoholic fatty liver disease (NAFLD), little is known about its progression to high-risk nonalcoholic steatohepatitis (NASH) in PsA patients. Shared disease mechanisms may explain the increased severity in PsA. This study involves two visits from PsA patients with NAFLD and active disease signs (e.g., swollen joint, enthesitis, or psoriatic plaque). It aims to assess the impact of biological therapies on liver disorders, joints, and skin in PsA patients.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages N/A and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Adults with diagnosis of PsA fulfilling the classification for PsA (CASPAR) criteria. 2. Must have: 1 or more swollen joint(s) and/or one or more active sites of enthesitis. 3. AND/OR.1 or more psoriatic plaques. 4. No changes in the regular medication regimen within the last three months, and no use of systemic and/or chronic steroids within 8 weeks leading up to the study. 5. Overweight or obese by BMI ≥ 25.0 kg/m2 or ≥ 23.0 for Asian participants. 6. Patients are starting Guselkumab therapy for PsA as indicated by primary rheumatologist. 7. Elevated liver fat on controlled attenuation parameter (CAP) ≥ 288 dB/m, which is consistent with NAFLD after exclusion of secondary causes of liver disease.

Exclusion Criteria:

1. Patients with prior exposure to IL12/23i, IL-17i, JAKi, or TYK2i. Patients with exposure to more than 2 TNFi. 2. Evidence of other causes of chronic liver disease.
  • - Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg).
  • - Previous or current infection with Hepatitis C as defined by presence of hepatitis C virus Abin serum (anti-HCV Ab).
  • - Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy.
  • - Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis.
  • - Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
  • - Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
  • - Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D.
  • - Drug-induced liver disease as defined on the basis of typical exposure and history.
  • - Bile duct obstruction as shown by imaging studies.
  • - History of gastrointestinal bypass surgery or ingestion of medications known to produce steatosis, such as corticosteroids, high-dose estrogen, tamoxifen, amiodarone or tetracycline in the previous 6 months.
  • - Evidence of cirrhosis or previously known cirrhosis based on the results from previous liver biopsy or history of portal hypertension presented by ascites, hepatic encephalopathy or varices.
  • - Presence of regular and/or excessive use of alcohol (defined as >30g/day for males and >15g/day for females) for a period longer than 2 years at any times in the last 10 years.
  • - Serum creatinine > 2.0 mg/dL.
  • - The subject is a pregnant or nursing female or is planning to become pregnant.
  • - Life expectancy less than 5 years.
3. History of known HIV infection

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06586281
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

N/A
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of California, San Diego
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Psoriatic Arthritis
Additional Details

Nonalcoholic fatty liver disease (NAFLD), ranging from benign steatosis to severe nonalcoholic steatohepatitis (NASH), is increasingly common and linked to cirrhosis. Patients with psoriatic arthritis (PsA) are at higher risk for NAFLD and NASH, partly due to methotrexate (MTX) use, which is associated with hepatotoxicity. Key cytokines involved in PsA, such as TNF, IL-17, and IL-23, may also contribute to NAFLD progression. The proposed study aims to explore shared pathogenic pathways in NAFLD and PsA by evaluating the role of IL-17/23 through imaging, metabolomics, and synovial biopsies. Ultrasound-guided synovial biopsy, a safe and effective method, will be used to obtain tissue samples, enabling the identification of new molecular signatures and therapeutic targets to improve treatment of joint diseases.

Arms & Interventions

Arms

Experimental: psoriatic arthritis patients

Adults with active PsA and diagnosed NAFLD

Interventions

Drug: - Guselkumab

This is a longitudinal study consisting of a two-time visit by psoriatic arthritis patients. The aim of the study is to determine the effect of biological therapies in liver disorders in patients with psoriatic arthritis.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of California, San Diego, San Diego, California

Status

Recruiting

Address

University of California, San Diego

San Diego, California, 92037

Site Contact

Mehrnaz Aghili

[email protected]

858-246-4721