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

May 15, 2019 updated by: Mehdi Yousefi, Tabriz University of Medical Sciences

The Effects of Oral Nanocurcumin on Expression Levels of microRNAs and Treg Cells and Th17 Cells Development Factors in Ankylosing Spondylitis Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

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

21 years to 44 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

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
Experimental: Nanocurcumin Arm
Nanocurcumin capsules (the formulation of curcumin nanoparticles, Exirnanosina). Subjects randomized to Nanocurcumin Arm will receive 80 mg/day for 4 months.
Drug: Nanocurcumin
Nanocurcumin capsules (the formulation of curcumin nanoparticles, Exirnanosina). Subjects randomized to Nanocurcumin Arm will receive 80 mg/day for 4 months
Placebo Comparator: Placebo
Subjects randomized to Placebo Arm will receive placebo in the form of capsules for 4 months.
Drug: Placebo
Subjects randomized to Placebo Arm will receive placebo in the form of capsules for 4 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessments of Ankylosing Spondylitis Signs and Symptoms (BASDI)
Time Frame: 4 months after treatment
Number of Subjects With a Reduction in Signs and Symptoms
4 months after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mir-141, mir-155 and mir-200 expression
Time Frame: 4 months after treatment
qPCR method (mir-141, mir-155 and mir-200 induces differentiation of Th17 cells and increase inflammation)
4 months after treatment
Serum IL-17 levels
Time Frame: 4 months after treatment
Elisa method (Th17 cells produce inflammatory cytokine, IL17, and increase inflammation).
4 months after treatment
RORγt expression
Time Frame: 4 months after treatment
qPCR method (RoRγt, a transcription factor, induce Th17 cell differentiation and increase inflammation).
4 months after treatment
IL-17 expression
Time Frame: 4 months after treatment
qPCR method (Th17 cells produce inflammatory cytokine, IL17, and increase inflammation).
4 months after treatment
Th17 cells frequency
Time Frame: 4 months after treatment
Flowcytometry (Th17 cells produce inflammatory cytokine, IL17, and increase inflammation).
4 months after treatment
mir-27, mir-17 and mir-146a expression
Time Frame: 4 months after treatment
PCR method (mir-27, mir-17 and mir-146a induces differentiation of Treg cells)
4 months after treatment
Serum TGF-β, IL-10, IL-6 levels
Time Frame: 4 months after treatment
Elisa method (Treg cells produce anti-inflammatory cytokine, and decrease inflammation).
4 months after treatment
FoxP3 expression
Time Frame: 4 months after treatment
qPCR method (FoxP3, a transcription factor, induce Treg cell differentiation and decrease inflammation).
4 months after treatment
TGF-β, IL-10, IL-6 expression
Time Frame: 4 months after treatment
qPCR method (Treg cells produce anti-inflammatory cytokine, and decrease inflammation).
4 months after treatment
Treg cells frequency
Time Frame: 4 months after treatment
Flowcytometry (Treg cells produce anti-inflammatory cytokine, and decrease inflammation).
4 months after treatment

Collaborators and Investigators

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

Sponsor

Tabriz University of Medical Sciences

Investigators

  • Study Director: Mehdi Yousefi, Ph.D, SCARM Institute
  • Study Director: Mehrzad Hajaliloo Bonab, Rheumatology, Tabriz University of Medical Sciences, Tabriz, Iran

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 (Actual)

April 29, 2017

Primary Completion (Actual)

November 7, 2017

Study Completion (Actual)

January 18, 2018

Study Registration Dates

First Submitted

April 28, 2017

First Submitted That Met QC Criteria

May 2, 2017

First Posted (Actual)

May 4, 2017

Study Record Updates

Last Update Posted (Actual)

May 17, 2019

Last Update Submitted That Met QC Criteria

May 15, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TabrizUMS-Rheumatology-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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