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Evaluating the Effect of Digoxin and Ursodeoxycholic Acid in Patients With Rheumatoid Arthritis

Phase 2
Completed
Conditions
Rheumatoid Arthritis
Interventions
Drug: Ursodeoxycholic acid (UDCA) 500 mg
Drug: Placebo
Registration Number
NCT04834557
Lead Sponsor
Tanta University
Brief Summary

The purpose of this study is to investigate the potential therapeutic effects of the cardiac glycoside digoxin and 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 cardiac glycoside digoxin and 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 90 rheumatoid arthritis patients who will meet the inclusion criteria will be enrolled in this study. The 90 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, 30 rheumatoid arthritis patients who will receive DMARDs + digoxin 25 mg every other day for 24 weeks and the last 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 digoxin and UDCA in the treatment of rheumatoid arthritis.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
90
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 digoxin or 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Ursodeoxycholic acid (UDCA)Ursodeoxycholic acid (UDCA) 500 mgParticipants in this arm will receive ursodeoxycholic acid (UDCA) 500 mg/day + DMARDs for 24 weeks.
ControlPlaceboParticipants in this arm will receive Placebo with the current DMARDs treatments for rheumatoid arthritis for 24 weeks.
DigoxinDigoxin 0.25 mgParticipants in this arm will receive digoxin 0.25 mg every other day + DMARDs for 24 weeks.
Primary Outcome Measures
NameTimeMethod
Changes from Baseline in Clinical Disease Activity Index (CDAI) ScoreBaseline, after 12 weeks, after 24 weeks

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 Index (CDAI) scores. A lower CDAI score from Baseline would mean improvement in disease activity and an increase in CDAI score from Baseline would mean an increase in disease activity or a worsening in disease activity. Scores: 0.0-2.8 = Range for Remission; 2.9-10.0 = Range for Low disease activity; 10.1-22.0 Range for Moderate disease activity; 22.1-76 Range for High disease activity. Total range is from 0-100, with the high scores representing high disease activity.

Changes in C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR)Baseline, after 12 weeks, after 24 weeks

C- reactive Protein (CRP) values and Erythrocyte Sedimentation Rate (ESR) will be made at baseline and after 12 as well as 24 weeks to determine the number of patients whose test result improved or worsened CRP value (normal range \<1.0 mg/dl). ESR (normal range 0-28 mm/hr) . If the value is increased, the disease activity worsened. If the value is reduced the disease activity is improved.

Secondary Outcome Measures
NameTimeMethod
Changes from baseline Measurement of IL-17A and HIF-1α at 12 and 24 weeksBaseline, after 12 weeks, after 24 weeks

Serum IL-17A and HIF-1α levels 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 eventsBaseline, after 12 weeks, after 24 weeks

The adverse events in each group will be observed and documented during the whole procedure to show the safety of the treatment.

Trial Locations

Locations (1)

Menoufia University Hospital

🇪🇬

Shibīn Al Kawm, Egypt

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