Clinical Study Evaluating the Effect of Carvedilol in Patients With Active Rheumatoid Arthritis

Sponsor

Tanta University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06108518

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study aims at investigating the possible efficacy and safety of carvedilol as an adjunctive therapy in patients with active rheumatoid arthritis and hypertension.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Carvedilol	Early Phase 1

Detailed Description

heumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. It is characterized with chronic production of pro-inflammatory cytokines, which lead to cartilage and bone degradation that results in tissue destruction by the patients' immune system (Guo et al., 2018).

The high systemic inflammatory burden associated with RA appears to be a key driver of increased CV risk. This inflammatory state is linked to endothelial dysfunction and accelerated atherosclerosis (Giollo et al., 2018). Consequently, RA increases the risk of cardiovascular (CV) mortality by up to 50% compared with the general population and CV disease is the leading cause of death in RA patients. This leads to suggestion that reducing inflammation lowers CV risk in RA (Dijkshoorn et al., 2022).

Therapies targeting inflammation remain the mainstay of RA treatment such as non- steroidal anti-inflammatory drugs (NSAIDs), non-biologic and biologic disease-modifying anti-rheumatic drugs (DMARDs), immune-osuppressants, and corticosteroids. However, current treatment strategies have many adverse effects and a significant proportion of RA patients did not effectively respond to them (Aletaha and Smolen., 2018). Consequently, it is crucial to find new therapeutic approaches for the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients.

Carvedilol is a non-selective β-blocker with α-adrenergic receptor antagonism properties which has been safely used in treatment of several cardiovascular disorders (Prajapati et al., 2017). Previous animal studies highlights evidences for the promising anti- arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) and eicosanoids including prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) (Arab and El-Sawalhi, 2013; Ahmed et al., 2017; Osman et al., 2017).

Taken together, carvedilol has powerful antioxidant/anti-inflammatory properties; we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

randomized, double blind placebo controlled parallel studyrandomized, double blind placebo controlled parallel study

Masking:

Double (Participant, Investigator)

Masking Description:

The blindness will be maintained by the similarity between the placebo and carvedilol tablets. The patients will be randomized by a neutral researcher using sealed envelope method with assigned code into two groups

Primary Purpose:

Other

Official Title:

Clinical Study Evaluating the Effect of Carvedilol in Patients With Active Rheumatoid Arthritis

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control group Group1 (Placebo group; n=35) which will receive the standard treatment for RA plus placebo tablet for 3 months.	Drug: Carvedilol Treatment group will take carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months.
Active Comparator: Treatment group Group 2 (Carvedilol group; n=35) which will receive the standard treatment for RA plus carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months.	Drug: Carvedilol Treatment group will take carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months.

Arm

Intervention/Treatment

Placebo Comparator: Control group

Group1 (Placebo group; n=35) which will receive the standard treatment for RA plus placebo tablet for 3 months.

Drug: Carvedilol

Treatment group will take carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months.

Active Comparator: Treatment group

Group 2 (Carvedilol group; n=35) which will receive the standard treatment for RA plus carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months.

Drug: Carvedilol

Treatment group will take carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months.

Outcome Measures

Primary Outcome Measures

change in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores. [12 week]
By the end of the study we should notice decrease in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores.

Secondary Outcome Measures

change in the serum level of the assessed biological markers [12 week]
By the end of the study we should notice decrease in serum level of the assessed biological markers C-reactive protein (CRP). 8-hydroxydeoxyguanosine (8-OHdG). Interlukin-6 (IL-6). Leukotriene B4 (LTB4

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with active rheumatoid arthritis (not in remission) according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria i.e 28 joints disease activity score (DAS-28) >2.6.
Patients with hypertension who are candidate to carvidolol.
Age range between 18 and 60 years old.
The studywillbecarriedoutbetween June 2023 and June 2025.
Both sexes.
Sex ratio, body mass index (BMI), age, disease activity, and disease duration matched patients.
Patients receive matched doses of standard treatment including methotrexate, non-steroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, acetaminophen, and low dose of oral corticosteroids (prednisolone < 15 mg) will be allowed to be enrolled the trial.
Intravenous, intra-articular or intramuscular corticosteroids; intra-articular hyaluronate sodium and biological DMARDs will not be permitted less than 4 weeks before the first dose of carvedilol.

Exclusion Criteria:

Patients with congestive heart failure, other heart disease (arrhythmia, ischemic heart disease including angina and myocardial infarction).
Patients with other inflammatory diseases and active infection.
Patients with glaucoma.
Patients with asthma, COPD, other lung diseases.
Patients with hepatic and biliary diseases.
Patients with chronic renal failure or those on dialysis.
Patients with peripheral intermittent claudication and peripheral circulatory disorders.
Patients receiving oral pednisolone greater than 15 mg/day.
Patients receiving biological DMARDs.
Patients with hypersensitivity to carvedilol.
Patients using antioxidants.
Pregnant and lactating females.
Patients receiving digitalis, anti-arrhythmic (amiodarone, propafenone) MAOI, cyclosporine, calcium channel blockers (verapamil, deltiazem), beta blockers, other antihypertensive medications hepatic microsomal enzymes inducers or inhibitors (phenytoin, rifampin, valoproate), oral hypoglycemic and insulin to avoid potential pharmacodynamics