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

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ClinicalTrials.gov Identifier: NCT04757571
Recruitment Status : Recruiting
First Posted : February 17, 2021
Last Update Posted : February 22, 2022
Sponsor:
Information provided by (Responsible Party):
Mahmoud Samy Abdallah, Sadat City University

Study Description
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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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Paroxetine Drug: Placebo Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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.
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Paroxetine
Paroxetine 20 mg daily plus standard therapy
 Drug: Paroxetine
Paroxetine 20 mg tablet plus standard therapy
Placebo Comparator: Placebo
Placebo tablet daily plus standard therapy
 Drug: Placebo
Placebo tablet plus standard therapy


Outcome Measures
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Primary Outcome Measures :
  1. ACR 20% improvement criteria (ACR20) response rate [ Time Frame: week 12 ]
    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

  2. ACR50 & ACR70 response rate [ Time Frame: week 12 ]
    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

  3. Disease activity scale in 28 joints (DAS-28) [ Time Frame: week 12 ]
    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).


Secondary Outcome Measures :
  1. GRK2 expression [ Time Frame: week 12 ]
    GRK2 expression in serum

  2. TNF-α [ Time Frame: week 12 ]
    Serum level Tumor necrosis factor- alpha (TNF-α)

  3. Inteleukins [ Time Frame: 12 weeks ]
    Serum levels of Interleukins (IL) IL-17, IL-1β , IL-6 & IL-10

  4. CRP [ Time Frame: 12 weeks ]
    Serum level of C-reactive protein (CRP)

  5. Drug Adverse effects [ Time Frame: 12 weeks ]
    Adverse effect incidence: adverse effect will be reported by patients or their caregivers and recorded by investigator.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04757571


Locations
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Egypt
Faculty of Pharmacy Recruiting
Shibīn Al Kawm, Menoufia, Egypt, 13829
Contact: Mahmoud S Abdallah, PhD    01063340887    Mahmoud.samy@fop.usc.edu.eg   
Contact    +201063340887    Mahmoud.samy@fop.usc.edu.eg   
Sponsors and Collaborators
Sadat City University
More Information
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Responsible Party: Mahmoud Samy Abdallah, Lecturer of Clinical Pharmacy, Sadat City University
ClinicalTrials.gov Identifier: NCT04757571    
Other Study ID Numbers: RS10/2021
First Posted: February 17, 2021    Key Record Dates
Last Update Posted: February 22, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Paroxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
 Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors