The Effects of Nanocurcumin on Treg Cells and Th17 Cells Responses in Ankylosing Spondylitis Patients
Condition: Ankylosing Spondylitis
MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
Study type: Interventional
Phase: Phase 2

Summary: 
      Ankylosing Spondylitis (AS) is a chronic rheumatic disease that principally affects the
      intervertebral and sacroiliac joints. Two major features of AS are inflammation and bone
      reformation. Th17 cells as a new subpopulation of CD4+ T cells, are characterized by the
      production of pro-inflammatory cytokines. Th17 cells have been implicated in autoimmune
      diseases, pathogenesis and diagnosis of several inflammatory diseases, such as AS. Regulatory
      T cells (Treg) with suppressive effects on inflammation and autoimmunity have been reported
      to implicate in pathology of AS. The Treg /Th17 functional balance is essential for the
      prevention of autoimmune and inflammatory diseases by preventing deleterious impairment to
      the host and mounting effective immune responses. A group of circulating miRNA in plasma is
      found to be the change they can be involved in inflammation or inhibit it. miRNAs have been
      shown to play a pivotal role in the pathogenesis of various diseases including autoimmune or
      auto-inflammatory diseases.The function and molecular pathways of several key deregulated
      miRNAs, are elucidated in AS patients. Curcumin is an active component of turmeric which is a
      perennial plant. Curcumin is able to exert anti-atherogenic, anti-cancer and
      anti-inflammatory effects. The curcumin induces down-regulation of various inflammatory
      cytokines including TNF-α and IL-1. The solubility of curcumin in nanomicelles spherical
      water increases to more than 100 thousand times, which significantly enhances the absorption
      of curcumin. The aim of the present study was to understand the nano-curcumin effects on
      frequency of Treg and Th17 cells, expression levels of their associated transcription factors
      and cytokines, secretion levels of their associated cytokines and also related miRNAs
      expression levels in peripheral blood of patients with AS and their correlation with the
      disease progression.
    

Detailed description: 
      A16-weeks randomized placebo-controlled study was conducted on a total of 24 patients with
      age range of 22 to 50, who were clinically diagnosed with ankylosing spondylitis on the basis
      of clinical manifestations. The AS patients were divided into 2 subgroup with a block
      randomization, 12 out of 24 received a daily dose of 80 mg oral nano-curcumin and 12 patients
      received placebo as control group in a period of 4 months. Peripheral blood samples (8 ml)
      were obtained from the patients in both control and treatment groups before and after
      nano-curcumin treatment for 4 months. PBMCs were isolated from samples using Ficoll
      separation technique. Subsequently, cells were cultured in the presence of PMA. Treg cells
      associated immunological parameters such as mRNA expression levels of mir-146a, mir-27 and
      mir-17, TGF-β, IL-10, IL-6 and FoxP3 and alsoTh17 related immunological parameters such as
      mRNA expression of mir-141, mir-155 and mir-200, IL-17, IL-23 and RORγt were measured by
      real-time PCR, also Treg and Th17 frequency and their related cytokines secretion levels were
      evaluated respectively by flowcytometry and ELISA technique in both groups, pre and
      post-treatment.
    

Intervention name(s): Nanocurcumin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Nanocurcumin capsules (the formulation of curcumin nanoparticles, Exirnanosina). Subjects randomized to Nanocurcumin Arm will receive 80 mg/day for 4 months; Subjects randomized to Placebo Arm will receive placebo in the form of capsules for 4 months
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Ankylosing spondylitis, Nanocurcumin, MicroRNA, Th17 cells