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

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ClinicalTrials.gov Identifier: NCT03140657
Recruitment Status : Completed
First Posted : May 4, 2017
Last Update Posted : September 17, 2018
Sponsor:
Information provided by (Responsible Party):
Tabriz University of Medical Sciences

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.

Condition or disease Intervention/treatment Phase
Ankylosing Spondylitis Drug: Nanocurcumin Drug: Placebo Phase 2

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  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: The Effects of Oral Nanocurcumin on Expression Levels of microRNAs and Treg Cells and Th17 Cells Development Factors in Ankylosing Spondylitis Patients
Actual Study Start Date : April 29, 2017
Actual Primary Completion Date : November 7, 2017
Actual Study Completion Date : January 18, 2018

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Assessments of Ankylosing Spondylitis Signs and Symptoms (BASDI) [ Time Frame: 4 months after treatment ]
    Number of Subjects With a Reduction in Signs and Symptoms


Secondary Outcome Measures :
  1. 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)

  2. Serum IL-17 levels [ Time Frame: 4 months after treatment ]
    Elisa method (Th17 cells produce inflammatory cytokine, IL17, and increase inflammation).

  3. RORγt expression [ Time Frame: 4 months after treatment ]
    qPCR method (RoRγt, a transcription factor, induce Th17 cell differentiation and increase inflammation).

  4. IL-17 expression [ Time Frame: 4 months after treatment ]
    qPCR method (Th17 cells produce inflammatory cytokine, IL17, and increase inflammation).

  5. Th17 cells frequency [ Time Frame: 4 months after treatment ]
    Flowcytometry (Th17 cells produce inflammatory cytokine, IL17, and increase inflammation).

  6. 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)

  7. 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).

  8. FoxP3 expression [ Time Frame: 4 months after treatment ]
    qPCR method (FoxP3, a transcription factor, induce Treg cell differentiation and decrease inflammation).

  9. TGF-β, IL-10, IL-6 expression [ Time Frame: 4 months after treatment ]
    qPCR method (Treg cells produce anti-inflammatory cytokine, and decrease inflammation).

  10. Treg cells frequency [ Time Frame: 4 months after treatment ]
    Flowcytometry (Treg cells produce anti-inflammatory cytokine, and decrease inflammation).



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Ages Eligible for Study:   23 Years to 46 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03140657


Locations
Iran, Islamic Republic of
Connective Tissue Diseases Research Center
Tabriz, Iran, Islamic Republic of, 0413
Sponsors and Collaborators
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:

Responsible Party: Tabriz University of Medical Sciences
ClinicalTrials.gov Identifier: NCT03140657     History of Changes
Other Study ID Numbers: TabrizUMS-Rheumatology-003
First Posted: May 4, 2017    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tabriz University of Medical Sciences:
Ankylosing spondylitis, Nanocurcumin, MicroRNA, Th17 cells

Additional relevant MeSH terms:
Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis