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

Rheumatoid Arthritis Clinical Trial

Official title:

The GRK2 Inhibitor Paroxetine as a Novel Adjunct to Conventional Therapy in Rheumatoid Arthritis Patients. A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04757571
• Other study ID #: RS10/2021
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: Sadat City University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Paroxetine
Paroxetine 20 mg tablet plus standard therapy
• Placebo
Placebo tablet plus standard therapy

Locations

Country	Name	City	State
Egypt	Faculty of Pharmacy	Shibin Al Kawm	Menoufia

Sponsors (1)

Lead Sponsor	Collaborator
Sadat City University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	GRK2 expression	GRK2 expression in serum	week 12
Secondary	TNF-a	Serum level Tumor necrosis factor- alpha (TNF-a)	week 12
Secondary	Inteleukins	Serum levels of Interleukins (IL) IL-17, IL-1ß , IL-6 & IL-10	12 weeks
Secondary	CRP	Serum level of C-reactive protein (CRP)	12 weeks
Secondary	Drug Adverse effects	Adverse effect incidence: adverse effect will be reported by patients or their caregivers and recorded by investigator.	12 weeks