Efficacy of JAK STAT Pathways Inhibitors in Treatment of Patients With Rheumatoid Arthritis

March 27, 2023 updated by: Adel A.Gomaa

Evaluation of the Efficacy of Natural JAK_ STAT Pathways Inhibitors in Treatment of Patients With Rheumatoid Arthritis as a Complementary Medicine

There is no treatment that could utterly cure Rheumatoid arthritis (RA), but the disease is mainly improved by conventional disease-modifying anti rheumatic drugs. Methotrexate and biological DMARDs as JAK-STAT inhibitors may be used to control and delay the progression of the disease and improve the quality of lives of patients. However, DMARDs have deleterious effects on human health. Several natural components have JAK-STAT inhibitory effect such as Boswellic acid (Boswellia serrata extract), Glycyrrhizin (Glycyrrhiza glabra extr.) and Apigenin (Chamomile extr)

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Rheumatoid arthritis (RA) is a systemic chronic, progressive, autoimmune disease characterized by inflammatory cell infiltration and synovial proliferation, accompanied by injury to articular cartilage and subchondral bone The prevalence of RA in women is 3.6% and 1.7% for men . There is no treatment that could utterly cure RA, but the disease is mainly improved by conventional disease-modifying antirheumatic drugs. Methotrexate and biological DMARDs as JAK-STAT inhibitors may be used to control and delay the progression of the disease and improve the quality of lives of patients. However, DMARDs have deleterious effects on human health. Chronic use of these agents by pregnant patients may induce teratogenic effects . Many studies showed that some natural plant extracts or mixed herbal compounds effectively regulate the immune system and possess in vitro and/or in vivo inhibitory effects against STAT to alleviate RA by inhibiting pro-inflammatory cytokines. Several natural components have JAK-STAT inhibitory effect such as Boswellic acid (Boswellia serrata extract), Glycyrrhizin (Glycyrrhiza glabra extr.) and Apigenin (Chamomile extr.). Boswellic acid and its derivative acetyl-11- keto boswellic acid, are reported to be the most potent inhibitors in the synthesis of 5-LOX. Since 5-LOX is an important enzyme involved in the biosynthesis of leukotrienes and is significantly expressed in RA. B. serrata extract, when administered orally, inhibits IL-6, IL-1 , IFN- TNF- and PGE2 in complete Freund's adjuvant-induced arthritis in rats. Glycyrrhizin reduced the activity of JAK/STAT signaling pathway, which is the upstream regulator of HMGB1. These natural products have inhibitory effect for the STAT3 signaling pathway that have anti-inflammatory and anti-rheumatoid as well as anticancer effects. These inhibitors have been found to inhibit the STAT3 signaling pathway by reducing IL-6 production . Apigenin is a plant-derived flavonoid that is abundant in celery, Chamomile, plantain seed, and is effective in the prevention and treatment of inflammatory diseases, prostate cancer, and in inhibiting tumorigenesis and angiogenesis in melanoma, breast, skin, and colon cancers. Apigenin reduced p-JAK1/2 and p-STAT3 in breast cancer (BT-474) cells, and demonstrated antirheumatic and anticancer activity by inhibiting JAK-STAT . our aim To assess the efficacy of some natural JAK-STAT inhibitors as complementary medicine in the treatment of rheumatoid arthritis and attenuation of the side effects of regular methotrexate our Research outcome measures:

  1. Primary (main):

    1. The change in DAS28 based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index (CDAI)
    2. Rate of achieving 20%, 50% and 70% improvement in the American College Rheumatology criteria (ACR20, ACR50, ACR70).

  2. Secondary (subsidiary):

    1. Change in visual analogue scale (VAS).
    2. Determination of effusion synovitis volume on musculoskeletal ultrasound(MSUS)
    3. Determination of Inflammatory cytokines levels: (Tumour necrosis factor α and Interleukin 6).
    4. Safety and Tolerability Measures: adverse events including nausea, vomiting, dizziness and abdominal pain, CBC and urine analysis as well as kidney and liver function tests will be performed before enrolment.

Study Type

Interventional

Enrollment (Anticipated)

75

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female,ages18-60.
  • Patients who met criteria for the diagnosis of RA
  • Patients who were signed the informed consent form.

Exclusion Criteria:

  • Patients with Malignant tumours,
  • Patients with Infectious diseases,
  • Patients with Hematologic diseases.
  • Patients with other rheumatic diseases.

  • Women who are pregnant or breastfeeding.

    • Hypersensitivity to dietary supplement used in this study.
    • Hypertensive patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: "apigenin" and "glycyrrhizin"
Patients will receive one capsule contains 10 mg of apigenin (Matricaria chamomilla L extract) and one capsule contains glycyrrhizin 50(licorice extract) twice daily for 6 months
Dietary supplement: "apigenin" and "glycyrrhizin"
"apigenin" will be administered as capsule (10mg,eq 200mg Matricaria chamomilla L extract) two times daily. Also, "glycyrrhizin " will be administered as capsule(50 mg eq 250 mg licorice extract) two times daily. The two types of capsules administration will be continue for 6 months
Active Comparator: "boswellic acid" and "glycyrrhizin"
Patients will receive one capsule contains 200 mg boswellic acid (Boswellia serrata extract) and one capsule contains glycyrrhizin 50(licorice extract) twice daily for 6 months
Dietary supplement: "glycyrrhizin" and "boswellic acid"
"boswellic acid" will be administered as capsule (200mg,eq 250mg Boswellia serrata extract) two times daily. Also, "glycyrrhizin " will be administered as capsule(50 mg eq 250 mg licorice extract) two times daily. The two types of capsules administration will be continue for 6 months
Placebo Comparator: "placebo"
Patients will receive daily two capsules contain placebo for 6 months
Dietary supplement: "placebo"
"Placebo "capsule will be administered two times daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The change in DAS28 based on C-reactive protein (DAS28-CRP)
Time Frame: Before the intervention, 3 months after the intervention, and 6 months after the intervention
DAS-28 score: a DAS-28 score > 5.1 indicating high disease activity; 3.2< DAS-28 score≤5.1 indicates moderate disease activity; 2.6< DAS-28 score≤3.2 indicates low disease activity; DAS-28 score≤2.6 indicates basic disease remission
Before the intervention, 3 months after the intervention, and 6 months after the intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in visual analogue scale (VAS
Time Frame: Before the intervention, 3 months after the intervention, and 6 months after the intervention
each patient will be asked to indicate his or her current level of pain on 100mm scale.0scale indicate no pain and 100mm indicate worst pain imaginable
Before the intervention, 3 months after the intervention, and 6 months after the intervention
Determination of effusion synovitis volume on musculoskeletal ultrasound(MSUS)
Time Frame: Before the intervention, 3 months after the intervention, and 6 months after the intervention
Determination of effusion synovitis volume on musculoskeletal ultrasound
Before the intervention, 3 months after the intervention, and 6 months after the intervention
Determination of Inflammatory cytokines levels: (Tumour necrosis factor α and Interleukin 6).
Time Frame: Before the intervention, 3 months after the intervention, and 6 months after the intervention
laboratory test
Before the intervention, 3 months after the intervention, and 6 months after the intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Adel A.Gomaa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2023

Primary Completion (Anticipated)

July 1, 2025

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

February 27, 2023

First Submitted That Met QC Criteria

March 27, 2023

First Posted (Actual)

March 29, 2023

Study Record Updates

Last Update Posted (Actual)

March 29, 2023

Last Update Submitted That Met QC Criteria

March 27, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Natural JAK STAT Inhibitors

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will become available to interested investigators upon submitting a reasonable research request by email to A. Gomaa

(a.gomma@aun.edu.eg).

IPD Sharing Time Frame

July, 2025

IPD Sharing Access Criteria

Data will become available to interested investigators upon submitting a reasonable research request by email to A. Gomaa

(a.gomma@aun.edu.eg).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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