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

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 2

Locations

Egypt

Study Type

Interventional

Intervention

Placebo

Digoxin 0.25 mg

Ursodeoxycholic acid (UDCA) 500 mg

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Digoxin, Ursodeoxycholic acid, Synovial inflammation, leukocyte infiltration, Autoimmune diseases, Th17 and Treg 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 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.

Sites / Locations

Menoufia University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Arm Label

Control

Digoxin

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 digoxin 0.25 mg every other day + DMARDs 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 Clinical Disease Activity Index (CDAI) 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 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)

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

Changes from baseline Measurement of IL-17A and HIF-1α at 12 and 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 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

NCT ID

NCT04834557

First Posted

April 2, 2021

Last Updated

March 21, 2023

Sponsor

Tanta University

1. Study Identification

Unique Protocol Identification Number

NCT04834557

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

November 1, 2021 (Actual)

Primary Completion Date

May 18, 2022 (Actual)

Study Completion Date

September 30, 2022 (Actual)

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

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis, Digoxin, Ursodeoxycholic acid, Synovial inflammation, leukocyte infiltration, Autoimmune diseases, Th17 and Treg 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

90 (Actual)

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

Digoxin

Arm Type

Experimental

Arm Description

Participants in this arm will receive digoxin 0.25 mg every other day + DMARDs for 24 weeks.

Arm Title

Ursodeoxycholic acid (UDCA)

Arm Type

Experimental

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)

Digoxin 0.25 mg

Intervention Description

All subjects will receive digoxin administered at 0.25 mg every other day 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 add-on treatment to the current DMARDs treatments for rheumatoid arthritis.

Primary Outcome Measure Information:

Title

Changes from Baseline in Clinical Disease Activity Index (CDAI) Score

Description

Time Frame

Baseline, after 12 weeks, after 24 weeks

Title

Changes in C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR)

Description

Time Frame

Baseline, after 12 weeks, after 24 weeks

Secondary Outcome Measure Information:

Title

Changes from baseline Measurement of IL-17A and HIF-1α at 12 and 24 weeks

Description

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.

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

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.

Overall Study Officials: