Evaluating the Effect of Ursodeoxycholic Acid in Patients With Rheumatoid Arthritis

NCT05973370 | Completed Phase 2

• 1 other identifier: Effect of UDCA on Rheumatoid
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the potential therapeutic effects of the secondary bile acid ursodeoxycholic acid (UDCA) on synovial inflammation and disease activity when administered as add-on treatments to the current DMARDs treatment for rheumatoid arthritis patients with variant disease activity.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; Ursodeoxycholic acid; Synovial inflammation; Th17 cells; Synovial hypoxia

Outcome Measures

Primary Outcomes (2)

• Changes in ACR20 response criteria

  The American College of Rheumatology (ACR) response criteria (ACR20) for rheumatoid arthritis (RA) has been widely adopted as measures of medication efficacy in clinical trials. The ACR20 response has been the preferred endpoint for clinical trials because it is the response shown to discriminate optimally between active treatment and placebo while identifying a few placebo-treated patients as improved.

  Baseline, after 12 weeks, after 24 weeks

• Changes from Baseline in DAS28-CRP activity Score

  To evaluate the effect of the use of UDCA as an add-on therapy in patients with rheumatoid arthritis by evaluating the change from baseline in the clinical findings as measured by Clinical Disease activity score 28 (DAS28-CRP) scores. A lower DAS28-CRP score from Baseline would mean improvement in disease activity and an increase in DAS28-CRP score from Baseline would mean an increase in disease activity or a worsening in disease activity.

  Baseline, after 12 weeks, after 24 weeks

Secondary Outcomes (4)

• Changes in ACR50 and ACR70 response criteria

  Baseline, after 12 weeks, after 24 weeks

• Changes in EULAR response criteria

  Baseline, after 12 weeks, after 24 weeks

• Changes from baseline Measurement of inflammatory markers (IL-17A, IL-23, HIF-1α, VEGF) at 12 and 24 weeks

  Baseline, after 12 weeks, after 24 weeks

• Numbers of participants with treatment-related adverse events

  Baseline, after 12 weeks, after 24 weeks

Study Arms (2)

Control

PLACEBO COMPARATOR

Participants in this arm will receive Placebo with the current DMARDs treatments for rheumatoid arthritis for 24 weeks.

Drug: Placebo

Ursodeoxycholic acid (UDCA)

ACTIVE COMPARATOR

Participants in this arm will receive ursodeoxycholic acid (UDCA) 500 mg/day + DMARDs for 24 weeks.

Drug: Ursodeoxycholic acid (UDCA) 500 mg

Interventions

Placebo DRUG

Placebo will be administered to the control group for 24 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.

Control

Ursodeoxycholic acid (UDCA) 500 mg DRUG

All subjects will receive Ursodeoxycholic acid (UDCA) administered at 500 mg/day for 24 weeks as an addon treatment to the current DMARDs treatments for rheumatoid arthritis.

Ursodeoxycholic acid (UDCA)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with rheumatoid arthritis according to the ACR/EULAR 2010 criteria.
• Having active rheumatoid arthritis disease activity (the 28-joint disease activity score \[DAS28\] according to the CRP formula \> 2.6).
• Aged between 18 and 80 years.
• With clear consciousness and able to cooperate with this study.
• Personal willingness and ability to comply with the study follow-up schedule and other requirements of the study protocol.
• Both male and female will be included
• All patients receiving non-biological drugs will be also included.
• Sign an informed consent for the clinical study.

You may not qualify if:

• Pregnant or planning to be pregnant and breast-feeding women
• Patients suffering from any chronic diseases
• Patients with other autoimmune diseases, such as systemic lupus erythematosus, Sjogren's syndrome and mixed connective tissue disease.
• Patients who have a diagnosis of any other inflammatory arthritis (e.g., psoriatic arthritis or ankylosing spondylitis).
• Patients with a history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis).
• Patients with a current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease.
• Patients treated with biological therapy such as TNF-α or IL-1β antagonists.
• Patients with infectious or inflammatory diseases, endocrine disorders, any past or current psychiatric or neurological diseases.
• Patients with cardiovascular diseases such as arrhythmias and acute myocardial infarction.
• Patients with electrolyte disturbances (such as hypokalemia, hypomagnesemia, and hypercalcemia) could potentially elevate the risk of digoxin toxicity.
• Patients with clinically significant hepatic and renal dysfunction or impairment.
• Alcohol abuse
• Patients with evidence of viral (HBV or HCV), autoimmune hepatitis, and decompensated liver disease.
• Patients with cancer currently diagnosed or in medical history, if no recovery was achieved.
• Patients who are allergic to Ursodeoxycholic acid (UDCA)

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Menoufia University Hospital

Shibīn al Kawm, Egypt

Location

Related Publications (4)

• Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81. doi: 10.1002/art.27584.

  PMID: 20872595 BACKGROUND

• Neogi T, Aletaha D, Silman AJ, Naden RL, Felson DT, Aggarwal R, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Khanna D, Kvien TK, Laing T, Liao K, Mease P, Menard HA, Moreland LW, Nair R, Pincus T, Ringold S, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G; American College of Rheumatology; European League Against Rheumatism. The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report. Arthritis Rheum. 2010 Sep;62(9):2582-91. doi: 10.1002/art.27580.

  PMID: 20872596 BACKGROUND

• Lee EJ, Kwon JE, Park MJ, Jung KA, Kim DS, Kim EK, Lee SH, Choi JY, Park SH, Cho ML. Ursodeoxycholic acid attenuates experimental autoimmune arthritis by targeting Th17 and inducing pAMPK and transcriptional corepressor SMILE. Immunol Lett. 2017 Aug;188:1-8. doi: 10.1016/j.imlet.2017.05.011. Epub 2017 May 21.

  PMID: 28539269 BACKGROUND

• O'Dwyer AM, Lajczak NK, Keyes JA, Ward JB, Greene CM, Keely SJ. Ursodeoxycholic acid inhibits TNFalpha-induced IL-8 release from monocytes. Am J Physiol Gastrointest Liver Physiol. 2016 Aug 1;311(2):G334-41. doi: 10.1152/ajpgi.00406.2015. Epub 2016 Jun 23.

  PMID: 27340129 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Nageh Ahmed El-Mahdy, Professor

  Professor of Pharmacology and Toxicology Faculty of Pharmacy, Tanta University

  STUDY CHAIR

• Medhat Ismail Abdel Hamid, Professor

  Professor of Pharmacology and Toxicology Faculty of Medicine, Al-Azhar University

  STUDY CHAIR

• Dalia Salah Seif, Associate Professor

  Associate Professor of Physical Medicine, Rheumatology and Rehabilitation Faculty of Medicine, Menoufyia University

  STUDY DIRECTOR

• Enass Yousef Osman, PHD

  Lecturer of Pharmacology and toxicology, Faculty of Pharmacy, Tanta University

  STUDY DIRECTOR

• Mariam George Tadros Bolous, Master

  Assistant Lecturer of Clinical pharmacy, Faculty of Pharmacy, Sinai University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer of Clinical pharmacy, Faculty of Pharmacy, Sinai University

Model Details: This is a randomized, prospective, placebo-controlled study that will be conducted on 60 patients who fulfill the selection criteria and will be classified randomly into two groups.

Study Record Dates

• First Submitted: July 23, 2023
• First Posted: August 2, 2023
• Study Start: May 1, 2023
• Primary Completion: November 30, 2023
• Study Completion: May 30, 2024
• Last Updated: June 3, 2024

Record last verified: 2024-05

Locations

EG (1)