Ankylosing SpondylitisPhase 2NCT03140657
The Effects of Nanocurcumin on Treg Cells and Th17 Cells Responses in Ankylosing Spondylitis Patients
A Phase 2 study testing Nanocurcumin in people with Ankylosing Spondylitis, run by Tabriz University of Medical Sciences at 1 site in Iran.
Trial 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. Read more about this study
- Who is it for?
- Ages 23 to 46 years
- Conditions the study is for
- Ankylosing Spondylitis
- What is being tested?
- Nanocurcumin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteIran
- Study dates
- 29 Apr 2017to 18 Jan 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 23 to 46 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Ankylosing Spondylitis
- Being tested
- Nanocurcumin, Placebo
- Keywords
- Ankylosing spondylitis, Nanocurcumin, MicroRNA, Th17 cells
- Medical subject headings
- Spondylitis, Ankylosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NanocurcuminDrug
Nanocurcumin capsules (the formulation of curcumin nanoparticles, Exirnanosina). Subjects randomized to Nanocurcumin Arm will receive 80 mg/day for 4 months
PlaceboDrug
Subjects randomized to Placebo Arm will receive placebo in the form of capsules for 4 months
| Study group | Role | What they receive |
|---|---|---|
| Nanocurcumin Arm | Experimental | Nanocurcumin capsules (the formulation of curcumin nanoparticles, Exirnanosina). Subjects randomized to Nanocurcumin Arm will receive 80 mg/day for 4 months. Receives: Drug: Nanocurcumin |
| Placebo | Placebo comparator | Subjects randomized to Placebo Arm will receive placebo in the form of capsules for 4 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessments of Ankylosing Spondylitis Signs and Symptoms (BASDI)
Number of Subjects With a Reduction in Signs and Symptoms
Measured: 4 months after treatment
Secondary outcomes (10)
mir-141, mir-155 and mir-200 expression
qPCR method (mir-141, mir-155 and mir-200 induces differentiation of Th17 cells and increase inflammation)
Measured: 4 months after treatment
Serum IL-17 levels
Elisa method (Th17 cells produce inflammatory cytokine, IL17, and increase inflammation).
Measured: 4 months after treatment
RORγt expression
qPCR method (RoRγt, a transcription factor, induce Th17 cell differentiation and increase inflammation).
Measured: 4 months after treatment
IL-17 expression
qPCR method (Th17 cells produce inflammatory cytokine, IL17, and increase inflammation).
Measured: 4 months after treatment
Th17 cells frequency
Flowcytometry (Th17 cells produce inflammatory cytokine, IL17, and increase inflammation).
Measured: 4 months after treatment
mir-27, mir-17 and mir-146a expression
PCR method (mir-27, mir-17 and mir-146a induces differentiation of Treg cells)
Measured: 4 months after treatment
Serum TGF-β, IL-10, IL-6 levels
Elisa method (Treg cells produce anti-inflammatory cytokine, and decrease inflammation).
Measured: 4 months after treatment
FoxP3 expression
qPCR method (FoxP3, a transcription factor, induce Treg cell differentiation and decrease inflammation).
Measured: 4 months after treatment
TGF-β, IL-10, IL-6 expression
qPCR method (Treg cells produce anti-inflammatory cytokine, and decrease inflammation).
Measured: 4 months after treatment
Treg cells frequency
Flowcytometry (Treg cells produce anti-inflammatory cytokine, and decrease inflammation).
Measured: 4 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2017
- Study start29 Apr 2017
- Primary completion7 Nov 2017
- Study completion18 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Ankylosing SpondylitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tabriz University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mehdi Yousefi, Tabriz University of Medical Sciences
- Investigators
- Mehdi Yousefi, Ph.D, Study director, SCARM instituteMehrzad Hajaliloo Bonab, Rheumatology, Study director, Tabriz University of Medical Sciences, Tabriz, Iran
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03140657
- Sponsor's protocol ID
- TabrizUMS-Rheumatology-003
- Status last verified
- May 2019
- First submitted
- 28 Apr 2017
- Last updated
- 17 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25452811Jethwa 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.
PubMed 26080615Wang 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.
PubMed 19247658Rao TS, Basu N, Siddiqui HH. Anti-inflammatory activity of curcumin analogues. Indian J Med Res. 1982 Apr;75:574-8. No abstract available.
PubMed 7118227Gupta 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.
PubMed 23143785Lv 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.
PubMed 26273623Du 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.
PubMed 19838199
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Oral Nanocurcumin on Expression Levels of microRNAs and Treg Cells and Th17 Cells Development Factors in Ankylosing Spondylitis Patients
- ClinicalTrials.gov ID
- NCT03140657
- Acronym / sponsor ID
- TabrizUMS-Rheumatology-003
- Conditions
- Ankylosing Spondylitis
- Keywords
- Ankylosing spondylitis, Nanocurcumin, MicroRNA, Th17 cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Tabriz University of Medical SciencesUniversity, hospital or other
- Study start
- 29 Apr 2017 (actual)
- Primary completion
- 7 Nov 2017 (actual)
- Study completion
- 18 Jan 2018 (actual)
- First posted
- 4 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nanocurcumin Arm | Experimental | Drug: NanocurcuminNanocurcumin capsules (the formulation of curcumin nanoparticles, Exirnanosina). Subjects randomized to Nanocurcumin Arm will receive 80 mg/day for 4 months. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects randomized to Placebo Arm will receive placebo in the form of capsules for 4 months. |
Who may qualify
- Ages
- 23 to 46 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NanocurcuminNanocurcumin capsules (the formulation of curcumin nanoparticles, Exirnanosina). Subjects randomized to Nanocurcumin Arm will receive 80 mg/day for 4 months | Drug | Nanocurcumin Arm |
| PlaceboSubjects randomized to Placebo Arm will receive placebo in the form of capsules for 4 months | Drug | Placebo |
Primary outcome
Assessments of Ankylosing Spondylitis Signs and Symptoms (BASDI)
Time frame: 4 months after treatment
Number of Subjects With a Reduction in Signs and Symptoms
10 secondary outcomes
mir-141, mir-155 and mir-200 expression
Time frame: 4 months after treatment
Serum IL-17 levels
Time frame: 4 months after treatment
RORγt expression
Time frame: 4 months after treatment
IL-17 expression
Time frame: 4 months after treatment
Th17 cells frequency
Time frame: 4 months after treatment
mir-27, mir-17 and mir-146a expression
Time frame: 4 months after treatment
Serum TGF-β, IL-10, IL-6 levels
Time frame: 4 months after treatment
FoxP3 expression
Time frame: 4 months after treatment
TGF-β, IL-10, IL-6 expression
Time frame: 4 months after treatment
Treg cells frequency
Time frame: 4 months after treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2019.
- Background: PubMed 25452811Wang 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.
- Background: PubMed 26080615Jethwa 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.
- Background: PubMed 19247658Wang 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.
- Background: PubMed 7118227Rao TS, Basu N, Siddiqui HH. Anti-inflammatory activity of curcumin analogues. Indian J Med Res. 1982 Apr;75:574-8. No abstract available.
- Background: PubMed 23143785Gupta 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.
- Background: PubMed 26273623Lv 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.
- Background: PubMed 19838199Du 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mehdi Yousefi, Ph.D study director
SCARM institute
Mehrzad Hajaliloo Bonab, Rheumatology study director
Tabriz University of Medical Sciences, Tabriz, Iran
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nanocurcumin in people with Ankylosing Spondylitis, run by Tabriz University of Medical Sciences at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessments of Ankylosing Spondylitis Signs and Symptoms (BASDI) (time frame: 4 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03140657, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2019.