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

Adel A.Gomaa

Status: Not yet enrolling

Conditions: Rheumatoid Arthritis

Treatments: Dietary Supplement: "placebo"; Dietary Supplement: "apigenin" and "glycyrrhizin"; Dietary Supplement: "glycyrrhizin" and "boswellic acid"

Study type: Interventional

Funder types: Other

Identifiers

NCT05788705

Natural JAK STAT Inhibitors

Details and patient eligibility

About

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)

Full 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.

Enrollment: 75 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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75 participants in 3 patient groups, including a placebo group

"apigenin" and "glycyrrhizin"

Active Comparator group

Description:

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

Treatment:

Dietary Supplement: "apigenin" and "glycyrrhizin"

"boswellic acid" and "glycyrrhizin"

Active Comparator group

Description:

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

Treatment:

Dietary Supplement: "glycyrrhizin" and "boswellic acid"

"placebo"

Placebo Comparator group

Description:

Patients will receive daily two capsules contain placebo for 6 months

Treatment:

Dietary Supplement: "placebo"