The Effects of Nanocurcumin on Treg Cells and Th17 Cells Responses in Ankylosing Spondylitis Patients

NCT03140657 | Completed Phase 2 DMC

• 1 other identifier: TabrizUMS-Rheumatology-003
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ankylosing Spondylitis

Keywords

Ankylosing spondylitis, Nanocurcumin, MicroRNA, Th17 cells

Outcome Measures

Primary Outcomes (1)

• Assessments of Ankylosing Spondylitis Signs and Symptoms (BASDI)

  Number of Subjects With a Reduction in Signs and Symptoms

  4 months after treatment

Secondary Outcomes (10)

• mir-141, mir-155 and mir-200 expression

  4 months after treatment

• Serum IL-17 levels

  4 months after treatment

• RORγt expression

  4 months after treatment

• IL-17 expression

  4 months after treatment

• Th17 cells frequency

  4 months after treatment

Study Arms (2)

Nanocurcumin Arm

EXPERIMENTAL

Nanocurcumin capsules (the formulation of curcumin nanoparticles, Exirnanosina). Subjects randomized to Nanocurcumin Arm will receive 80 mg/day for 4 months.

Drug: Nanocurcumin

Placebo

PLACEBO COMPARATOR

Subjects randomized to Placebo Arm will receive placebo in the form of capsules for 4 months.

Drug: Placebo

Interventions

Nanocurcumin DRUG

Nanocurcumin capsules (the formulation of curcumin nanoparticles, Exirnanosina). Subjects randomized to Nanocurcumin Arm will receive 80 mg/day for 4 months

Nanocurcumin Arm

Placebo DRUG

Subjects randomized to Placebo Arm will receive placebo in the form of capsules for 4 months

Placebo

Eligibility Criteria

• Age: 23 Years - 46 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Willingness to cooperate
• Aged 22 to 50 years
• The diagnosis of ankylosing spondylitis by rheumatologist
• Patients with a BASDAI \> 4 as having active disease.
• Disease duration 5-8 years

You may not qualify if:

• Nutritional supplements and antioxidant alpha-lipoic acid a month before the study.
• Pregnancy and lactation
• History of diabetes and other chronic diseases
• History of other autoimmune diseases
• Occurrence of relapses during the study period
• Acceptance rate of less than 70% of supplements
• Unwillingness to continue to cooperate

Sponsors & Collaborators

• Tabriz University of Medical Sciences: lead

Study Sites (1)

Connective Tissue Diseases Research Center

Tabriz, 0413, Iran

Location

Related Publications (7)

• Wang C, Liao Q, Hu Y, Zhong D. T lymphocyte subset imbalances in patients contribute to ankylosing spondylitis. Exp Ther Med. 2015 Jan;9(1):250-256. doi: 10.3892/etm.2014.2046. Epub 2014 Nov 4.

  PMID: 25452811 BACKGROUND

• Jethwa H, Bowness P. The interleukin (IL)-23/IL-17 axis in ankylosing spondylitis: new advances and potentials for treatment. Clin Exp Immunol. 2016 Jan;183(1):30-6. doi: 10.1111/cei.12670. Epub 2015 Sep 30.

  PMID: 26080615 BACKGROUND

• Wang X, Lin Z, Wei Q, Jiang Y, Gu J. Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis. Rheumatol Int. 2009 Sep;29(11):1343-7. doi: 10.1007/s00296-009-0883-x. Epub 2009 Feb 27.

  PMID: 19247658 BACKGROUND

• Rao TS, Basu N, Siddiqui HH. Anti-inflammatory activity of curcumin analogues. Indian J Med Res. 1982 Apr;75:574-8. No abstract available.

  PMID: 7118227 BACKGROUND

• Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013 Jan;15(1):195-218. doi: 10.1208/s12248-012-9432-8. Epub 2012 Nov 10.

  PMID: 23143785 BACKGROUND

• Lv Q, Li Q, Zhang P, Jiang Y, Wang X, Wei Q, Cao S, Liao Z, Lin Z, Pan Y, Huang J, Li T, Jin O, Wu Y, Gu J. Disorders of MicroRNAs in Peripheral Blood Mononuclear Cells: As Novel Biomarkers of Ankylosing Spondylitis and Provocative Therapeutic Targets. Biomed Res Int. 2015;2015:504208. doi: 10.1155/2015/504208. Epub 2015 Jul 26.

  PMID: 26273623 BACKGROUND

• Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, Li Z, Wu Z, Pei G. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol. 2009 Dec;10(12):1252-9. doi: 10.1038/ni.1798. Epub 2009 Oct 18.

  PMID: 19838199 BACKGROUND

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

nanocurcumin

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Study Officials

• Mehdi Yousefi, Ph.D

  SCARM institute

  STUDY DIRECTOR

• Mehrzad Hajaliloo Bonab, Rheumatology

  Tabriz University of Medical Sciences, Tabriz, Iran

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 4, 2017
• Study Start: April 29, 2017
• Primary Completion: November 7, 2017
• Study Completion: January 18, 2018
• Last Updated: May 17, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)