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

NCT05788705 | Unknown

• 1 other identifier: Natural JAK STAT Inhibitors
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

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)

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• The change in DAS28 based on C-reactive protein (DAS28-CRP)

  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 Outcomes (3)

• Change in visual analogue scale (VAS

  Before the intervention, 3 months after the intervention, and 6 months after the intervention

• Determination of effusion synovitis volume on musculoskeletal ultrasound(MSUS)

  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).

  Before the intervention, 3 months after the intervention, and 6 months after the intervention

Study Arms (3)

"apigenin" and "glycyrrhizin"

ACTIVE COMPARATOR

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"

"boswellic acid" and "glycyrrhizin"

ACTIVE COMPARATOR

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"

"placebo"

PLACEBO COMPARATOR

Patients will receive daily two capsules contain placebo for 6 months

Dietary Supplement: "placebo"

Interventions

"apigenin" and "glycyrrhizin" DIETARY_SUPPLEMENT

"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

"apigenin" and "glycyrrhizin"

"glycyrrhizin" and "boswellic acid" DIETARY_SUPPLEMENT

"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

"boswellic acid" and "glycyrrhizin"

"placebo" DIETARY_SUPPLEMENT

"Placebo "capsule will be administered two times daily for 6 months

"placebo"

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Adel A.Gomaa: lead

Related Publications (11)

• Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016 Oct 22;388(10055):2023-2038. doi: 10.1016/S0140-6736(16)30173-8. Epub 2016 May 3.

  PMID: 27156434 BACKGROUND

• Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018 Apr 27;6:15. doi: 10.1038/s41413-018-0016-9. eCollection 2018.

  PMID: 29736302 BACKGROUND

• Oton T, Carmona L. The epidemiology of established rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2019 Oct;33(5):101477. doi: 10.1016/j.berh.2019.101477. Epub 2020 Jan 25.

  PMID: 31987685 BACKGROUND

• Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, Germino R, Menon S, Sun Y, Wang C, Shapiro AB, Kanik KS, Connell CA; ORAL Surveillance Investigators. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med. 2022 Jan 27;386(4):316-326. doi: 10.1056/NEJMoa2109927.

  PMID: 35081280 BACKGROUND

• Hoisnard L, Pina Vegas L, Dray-Spira R, Weill A, Zureik M, Sbidian E. Risk of major adverse cardiovascular and venous thromboembolism events in patients with rheumatoid arthritis exposed to JAK inhibitors versus adalimumab: a nationwide cohort study. Ann Rheum Dis. 2023 Feb;82(2):182-188. doi: 10.1136/ard-2022-222824. Epub 2022 Oct 5.

  PMID: 36198438 BACKGROUND

• Yang J, Wang L, Guan X, Qin JJ. Inhibiting STAT3 signaling pathway by natural products for cancer prevention and therapy: In vitro and in vivo activity and mechanisms of action. Pharmacol Res. 2022 Aug;182:106357. doi: 10.1016/j.phrs.2022.106357. Epub 2022 Jul 19.

  PMID: 35868477 BACKGROUND

• Dudics S, Langan D, Meka RR, Venkatesha SH, Berman BM, Che CT, Moudgil KD. Natural Products for the Treatment of Autoimmune Arthritis: Their Mechanisms of Action, Targeted Delivery, and Interplay with the Host Microbiome. Int J Mol Sci. 2018 Aug 24;19(9):2508. doi: 10.3390/ijms19092508.

  PMID: 30149545 BACKGROUND

• Kumar R, Singh S, Saksena AK, Pal R, Jaiswal R, Kumar R. Effect of Boswellia Serrata Extract on Acute Inflammatory Parameters and Tumor Necrosis Factor-alpha in Complete Freund's Adjuvant-Induced Animal Model of Rheumatoid Arthritis. Int J Appl Basic Med Res. 2019 Apr-Jun;9(2):100-106. doi: 10.4103/ijabmr.IJABMR_248_18.

  PMID: 31041173 BACKGROUND

• Wu X, Wang W, Chen Y, Liu X, Wang J, Qin X, Yuan D, Yu T, Chen G, Mi Y, Mou J, Cui J, Hu A, E Y, Pei D. Glycyrrhizin Suppresses the Growth of Human NSCLC Cell Line HCC827 by Downregulating HMGB1 Level. Biomed Res Int. 2018 Jan 15;2018:6916797. doi: 10.1155/2018/6916797. eCollection 2018.

  PMID: 29568761 BACKGROUND

• Wu Y, Wang Z, Du Q, Zhu Z, Chen T, Xue Y, Wang Y, Zeng Q, Shen C, Jiang C, Liu L, Zhu H, Liu Q. Pharmacological Effects and Underlying Mechanisms of Licorice-Derived Flavonoids. Evid Based Complement Alternat Med. 2022 Jan 17;2022:9523071. doi: 10.1155/2022/9523071. eCollection 2022.

  PMID: 35082907 BACKGROUND

• Abid R, Ghazanfar S, Farid A, Sulaman SM, Idrees M, Amen RA, Muzammal M, Shahzad MK, Mohamed MO, Khaled AA, Safir W, Ghori I, Elasbali AM, Alharbi B. Pharmacological Properties of 4', 5, 7-Trihydroxyflavone (Apigenin) and Its Impact on Cell Signaling Pathways. Molecules. 2022 Jul 4;27(13):4304. doi: 10.3390/molecules27134304.

  PMID: 35807549 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Apigenin; Glycyrrhizic Acid; boswellic acid

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)

Flavones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pentacyclic Triterpenes; Triterpenes; Terpenes; Hydrocarbons; Organic Chemicals

Central Study Contacts

Adel A Gomaa, ph.D

CONTACT

01009534841; a.gomaa@aun.edu.eg

Safaa A Mahran, MD

CONTACT

01003385106; Safaa69@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PROF OF CLINICAL PHARMACOLOGY

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: March 29, 2023
• Study Start: July 1, 2023
• Primary Completion: July 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 29, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: July, 2025
• 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).