The GRK2 Inhibitor Paroxetine as a Novel Adjunct to Conventional Therapy in Rheumatoid Arthritis Patients

NCT04757571 | Withdrawn Phase 1 DMC

• 1 other identifier: RS10/2021
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Among three MAPK families, paroxetine was found to be able to decrease the phosphorylation of ERK. It was reported that paroxetine attenuates the symptoms of collage induced arthritis rats due to its inhibitory effect on T cell activation and infiltration to synovial tissue via suppression of ERK pathway. This study aimed to evaluate the therapeutic efficacy of paroxetine in rheumatoid arthritis. Paroxetine prevents the joint inflammation which is at the very early stage. paroxetine could inhibit GRK2 with selectivity over other GRKs. Medications developed for maintaining the immunologic equilibrium. such as GRK2 inhibitors, will be the novel trends in RA treatment that could avoid the adverse side effects that are common with current treatment options.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• ACR 20% improvement criteria (ACR20) response rate

  based on tender and swollen joint counts, patient's assessment of pain, patient and physician global assessment of arthritis, Health Assessment Questionnaire Disability Index (HAQ DI), and CRP level

  week 12

• ACR50 & ACR70 response rate

  based on tender and swollen joint counts, patient's assessment of pain, patient and physician global assessment of arthritis, Health Assessment Questionnaire Disability Index (HAQ DI), and CRP level

  week 12

• Disease activity scale in 28 joints (DAS-28)

  Scale assessing severity of rheumatoid arthritis based on number of tender, swollen joints, erythrocyte sedimentation rate (ESR) levels, and patient self-assessment of his condition (global health assessment). Whereas "28" describes the number of different joints including in the measurement: proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2), knees (2).

  week 12

Secondary Outcomes (5)

• GRK2 expression

  week 12

• TNF-α

  week 12

• Inteleukins

  12 weeks

• CRP

  12 weeks

• Drug Adverse effects

  12 weeks

Study Arms (2)

Paroxetine

EXPERIMENTAL

Paroxetine 20 mg daily plus standard therapy

Drug: Paroxetine

Placebo

PLACEBO COMPARATOR

Placebo tablet daily plus standard therapy

Drug: Placebo

Interventions

Paroxetine DRUG

Paroxetine 20 mg tablet plus standard therapy

Paroxetine

Placebo DRUG

Placebo tablet plus standard therapy

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with active rheumatoid arthritis based on DAS28 score. Patients received the standard therapy (i.e. one or more conventional DMARDs) for at least three months.

You may not qualify if:

• Known hypersensitivity to metformin.
• Patients who have a prior diagnosis with diabetes mellitus.
• Patients receive metformin for any other indications.
• Patients with congestive heart failure.
• Patients with a history of myocardial infarction.
• Patients with severe anemia.
• Patients with active infections or other inflammatory diseases.
• Patients receiving biological therapy.
• Pregnancy or lactation.
• Patients with impaired liver functions.
• Patients with impaired kidney functions (serum creatinine concentrations ≥1.5 and ≥1.4 mg/dL in males and females respectively).
• Patients with malignancies.

Sponsors & Collaborators

• Sadat City University: lead

Study Sites (1)

Faculty of Pharmacy

Shibīn al Kawm, Menoufia, 13829, Egypt

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Paroxetine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Clinical Pharmacy

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 17, 2021
• Study Start: February 1, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

EG (1)