Clinical trial NCT04834557: Evaluating the Effect of Digoxin and Ursodeoxycholic Acid in Patients With Rheumatoid Arthritis
Official title: Evaluating the Effect of Digoxin and Ursodeoxycholic Acid in Patients With Rheumatoid Arthritis in Egypt
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Digoxin
Ursodeoxycholic acid
Synovial inflammation
leukocyte infiltration
Autoimmune diseases
Th17 and Treg cells
Synovial hypoxia
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2021-04-08
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a randomized controlled prospective study
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Changes from Baseline in Clinical Disease Activity Index (CDAI) Score
timeFrame: Baseline, after 12 weeks, after 24 weeks
measure: Changes in C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR)
timeFrame: Baseline, after 12 weeks, after 24 weeks
Secondary outcomes:
measure: Changes from baseline Measurement of IL-17A and HIF-1α at 12 and 24 weeks
timeFrame: Baseline, after 12 weeks, after 24 weeks
measure: Numbers of participants with treatment-related adverse events
timeFrame: Baseline, after 12 weeks, after 24 weeks
Other outcomes:
Locations:
city: Shibīn Al Kawm
country: Egypt
facility: Menoufia University Hospital
Study officials:
affiliation: Professor of Pharmacology and Toxicology Faculty of Pharmacy, Tanta University
name: Nageh Ahmed El-Mahdy, Professor
role: STUDY_CHAIR
affiliation: Professor of Pharmacology and Toxicology Faculty of Medicine, Al-Azhar University
name: Medhat Ismail Abdel Hamid, Professor
role: STUDY_CHAIR
affiliation: Associate Professor of Physical Medicine, Rheumatology and Rehabilitation Faculty of Medicine, Menoufyia University
name: Dalia Salah Seif, PHD
role: STUDY_DIRECTOR
affiliation: Lecturer of Pharmacology and toxicology, Faculty of Pharmacy, Tanta University
name: Enass Yousef Osman, PHD
role: STUDY_DIRECTOR
affiliation: Assistant Lecturer of Clinical pharmacy, Faculty of Pharmacy, Sinai University
name: Mariam George Tadros Bolous, Master
role: PRINCIPAL_INVESTIGATOR
References:
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