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Evaluating the Effect of Ursodeoxycholic Acid in Patients With Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status
Recruiting
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Placebo
Ursodeoxycholic acid (UDCA) 500 mg
Sponsored by
Tanta University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Ursodeoxycholic acid, Synovial inflammation, Th17 cells, Synovial hypoxia

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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) Patients who are unconscious and unable to complete the study. Patients with acute inflammation of the gall bladder or the biliary tract, frequent episodes of biliary colic, and impaired contractility of the gall bladder, will be excluded. Patients with cholestasis, primary biliary cirrhosis, or biliary obstruction will also be excluded. Patients who have received an organ transplant.

Sites / Locations

  • Menoufia University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Control

Ursodeoxycholic acid (UDCA)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Changes from Baseline in DAS28-CRP activity Score
To evaluate the effect of the use of digoxin and 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.
Changes in ACR 20, ACR 50, ACR 70 response criteria
The American College of Rheumatology (ACR) response criteria criteria (ACR20, ACR50, ACR70) for rheumatoid arthritis (RA) have 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 few placebo-treated patients as improved

Secondary Outcome Measures

Changes from baseline Measurement of inflammatory markers (IL-17A, IL-23, HIF-1α, VEGF) at 12 and 24 weeks
Serum IL-17A, IL-23, VEGF and HIF-1α levels (pg/ml) will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturer's protocol.
Numbers of participants with treatment-related adverse events
The adverse events in each group will be observed and documented during the whole procedure to show the safety of the treatment.

Full Information

First Posted
July 23, 2023
Last Updated
August 1, 2023
Sponsor
Tanta University
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1. Study Identification

Unique Protocol Identification Number
NCT05973370
Brief Title
Evaluating the Effect of Ursodeoxycholic Acid in Patients With Rheumatoid Arthritis
Official Title
Evaluating the Effect of Ursodeoxycholic Acid in Patients With Rheumatoid Arthritis in Egypt
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
July 30, 2023 (Anticipated)
Study Completion Date
October 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tanta University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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 treatments for rheumatoid arthritis patients with variant disease activity.
Detailed Description
This study is a randomized, open-labeled, controlled prospective study to evaluate 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 treatments for rheumatoid arthritis patients with variant disease activity. The study population will be rheumatoid arthritis patients attending the Physical Medicine, Rheumatology and Rehabilitation Department at Menoufia University Hospital, Menoufia, Egypt. A total of 60 rheumatoid arthritis patients who will meet the inclusion criteria will be enrolled in this study. The 60 participants will be divided into 30 rheumatoid arthritis patients who will receive placebo + the current DMARDs treatments of rheumatoid arthritis for 24 weeks and serve as the control group, and 30 rheumatoid arthritis patients who will receive DMARDs + ursodeoxycholic acid (UDCA) 500 mg/day for 24 weeks. Clinical Examinations and laboratory parameters will be performed and measured at the beginning of the study, 12 weeks and 24 weeks after randomization to evaluate the efficacy of and UDCA in the treatment of rheumatoid arthritis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, Ursodeoxycholic acid, Synovial inflammation, Th17 cells, Synovial hypoxia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This study is a randomized controlled prospective study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Participants in this arm will receive Placebo with the current DMARDs treatments for rheumatoid arthritis for 24 weeks.
Arm Title
Ursodeoxycholic acid (UDCA)
Arm Type
Active Comparator
Arm Description
Participants in this arm will receive ursodeoxycholic acid (UDCA) 500 mg/day + DMARDs for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered to the control group for 24 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.
Intervention Type
Drug
Intervention Name(s)
Ursodeoxycholic acid (UDCA) 500 mg
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes from Baseline in DAS28-CRP activity Score
Description
To evaluate the effect of the use of digoxin and 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.
Time Frame
Baseline, after 12 weeks, after 24 weeks
Title
Changes in ACR 20, ACR 50, ACR 70 response criteria
Description
The American College of Rheumatology (ACR) response criteria criteria (ACR20, ACR50, ACR70) for rheumatoid arthritis (RA) have 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 few placebo-treated patients as improved
Time Frame
Baseline, after 12 weeks, after 24 weeks
Secondary Outcome Measure Information:
Title
Changes from baseline Measurement of inflammatory markers (IL-17A, IL-23, HIF-1α, VEGF) at 12 and 24 weeks
Description
Serum IL-17A, IL-23, VEGF and HIF-1α levels (pg/ml) will be measured by means of the human enzyme-linked immunosorbent assay (ELISA) technique according to the manufacturer's protocol.
Time Frame
Baseline, after 12 weeks, after 24 weeks
Title
Numbers of participants with treatment-related adverse events
Description
The adverse events in each group will be observed and documented during the whole procedure to show the safety of the treatment.
Time Frame
Baseline, after 12 weeks, after 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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) Patients who are unconscious and unable to complete the study. Patients with acute inflammation of the gall bladder or the biliary tract, frequent episodes of biliary colic, and impaired contractility of the gall bladder, will be excluded. Patients with cholestasis, primary biliary cirrhosis, or biliary obstruction will also be excluded. Patients who have received an organ transplant.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mariam George Tadros, Master
Phone
+20 1503030620
Email
mariam.tadros77@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Dalia Salah Seif, Associate Professor
Phone
+20 1008312704
Email
sdalia30@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nageh Ahmed El-Mahdy, Professor
Organizational Affiliation
Professor of Pharmacology and Toxicology Faculty of Pharmacy, Tanta University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Medhat Ismail Abdel Hamid, Professor
Organizational Affiliation
Professor of Pharmacology and Toxicology Faculty of Medicine, Al-Azhar University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Dalia Salah Seif, Associate Professor
Organizational Affiliation
Associate Professor of Physical Medicine, Rheumatology and Rehabilitation Faculty of Medicine, Menoufyia University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Enass Yousef Osman, PHD
Organizational Affiliation
Lecturer of Pharmacology and toxicology, Faculty of Pharmacy, Tanta University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Mariam George Tadros Bolous, Master
Organizational Affiliation
Assistant Lecturer of Clinical pharmacy, Faculty of Pharmacy, Sinai University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Menoufia University Hospital
City
Shibīn Al Kawm
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariam George Tadros Bolous, Master Degree
Phone
+20 1503030620
Email
mariam.tadros77@gmail.com
First Name & Middle Initial & Last Name & Degree
Dalia Salah Seif, Associate Professor
Phone
+20 1008312704
Email
sdalia30@gmail.com

12. IPD Sharing Statement

Citations:
PubMed Identifier
20872595
Citation
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.
Results Reference
background
PubMed Identifier
20872596
Citation
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.
Results Reference
background
PubMed Identifier
28539269
Citation
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.
Results Reference
background
PubMed Identifier
27340129
Citation
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.
Results Reference
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Evaluating the Effect of Ursodeoxycholic Acid in Patients With Rheumatoid Arthritis

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