The Immunomodulatory Effects of Oral Nanocurcumin in Multiple Sclerosis Patients
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 2
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
Nanocurcumin
Placebo
Sponsored by

About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple sclerosis, Nanocurcumin, MicroRNAs, Th17 cells, Treg cells
Eligibility Criteria
Inclusion Criteria:
- Willingness to cooperate
- Aged 18 to 65 years
- The diagnosis of Multiple sclerosis by Neurologist
- Patients in Relapsing Remitting (RRMS)
- Patients with Expanded Disability Status Scale (EDSS) <5/5.
Exclusion Criteria:
- Use of nutritional supplements and antioxidant and immunosuppressive drugs 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
Sites / Locations
- Drug Applied Research Center, Tabriz, Iran
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Patients who received nanocurcumin
Patients who received placebo
Arm Description
Patients who received nanocurcumin
Patients who received placebo
Outcomes
Primary Outcome Measures
EDSS measurment
EDSS measurment by neurologist
Secondary Outcome Measures
Treg cells frequency
Flowcytometry (Treg cells produce anti-inflammatory cytokines)
Th17 cells frequency
Flowcytometry (Th17 cells produce inflammatory cytokine and increase inflammation)
IL-17 and RORγt expression
qPCR method
IL-17 secretion levels
ELISA method
microRNAs (miRNA-326) expression
Evaluate the diagnostic value of microRNAs in quantitative polymerase chain reaction (qPCR), in MS patients as compared with healthy control
TGF-β and FoxP3 expression
qPCR method
TGF-β secretion levels
ELISA method
microRNAs (miRNA-106b and miRNA-25) expression
Evaluate the diagnostic value of microRNAs in quantitative polymerase chain reaction
Full Information
NCT ID
NCT03150966
First Posted
May 6, 2017
Last Updated
September 13, 2018
Sponsor
Tabriz University of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT03150966
Brief Title
The Immunomodulatory Effects of Oral Nanocurcumin in Multiple Sclerosis Patients
Official Title
The Effects of Oral Nanocurcumin on Expression Levels of microRNAs and Treg Cells and Th17 Cells Development Factors in Multiple Sclerosis Patients
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
June 8, 2016 (Actual)
Primary Completion Date
August 10, 2017 (Actual)
Study Completion Date
November 7, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tabriz University of Medical Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Multiple sclerosis is the most common autoimmune disease of the central nervous system, most ranging in age from 40-20 years of age is associated with neurons inflammation and demyelination. Increasing aggressive activities of Th17 and Th1 cells that their function is to secrete proinflammatory cytokines and decreasing the number and activity of regulatory T cells, which normally leads to controlling inflammation, are seen in these patients.Many studies have carried out to assess the prevalence of Tregs and Th17 in autoimmune disorders such as MS. The Treg /Th17 functional balance is necessary for the impediment of autoimmune and inflammatory diseases by preventing harmful injury to the host and increasing effective immune responses. miRNAs have been shown to play a pivotal role in the pathogenesis of various diseases including autoimmune or auto-inflammatory diseases. Curcumin, the active principle constituent of turmeric, is proved to be capable of regulating cellular responses and the growth of different cell types in the immune system such as B cells, T cells, macrophages, dendritic cells and natural killer cells. Curcumin has a combination of activities such as anti-inflammatory, antioxidant, anti-proliferation, anti-invasive, and can used in the treatment of Alzheimer's, Parkinson's, Multiple sclerosis, Cardiovascular disease, Bacterial diseases and Arthritis. The solubility of curcumin in nanomicelles spherical water increases to more than 100 thousand times, which significantly enhances the absorption of curcumin. The present study aimed at investigating the effects of nanocurcumin on the 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 MS.
.
Detailed Description
In this study, fresh blood samples were acquired from 50 MS patients introduced by corresponding physician and Neurologist. As the aim of the current study was the assessment of nanocurcumin in MS patients, the peripheral blood collection was collected in two steps. After the first blood collection via venipuncture, 25 patients received nanocurcumin capsules each day and the remaining 25 patients took placebo for 6 months. Accordingly, the second sampling from the mentioned population was collected after 6 months. 9 patients were excluded from the study: 3 did not provide informed consent, 5 lived quite far away from the place in which follow-up examinations were performed, and 1 patient developed cancer. In all cases, 15 ml of blood was utilized for peripheral blood mononuclear cells (PBMC) isolation. PBMC is used to measure the expression levels of miRNA-106b, miRNA-25 and miRNA-326. In this regard, specific kits extracted miRNA from cells is used. Then the version of miRNA using Quantitative Real time polymerase chain reaction(qPCR).Then the frequency of Treg and Th17 cells in peripheral blood of patients will be examined by Flowcytometry and compared to the control group. The expression of key transcription factor (Foxp3) and specific cytokines (TGF-β) related to the Treg cells and key transcription factor (RORγt) and specific cytokines, interleukin-17(IL-17), related to the Th17 are measured by Quantitative Real time PCR. Elisa methos is used to assess the amount of the cytokine TGF-β and IL-17 in cultured cells.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Multiple sclerosis, Nanocurcumin, MicroRNAs, Th17 cells, Treg cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Patients who received nanocurcumin
Arm Type
Experimental
Arm Description
Patients who received nanocurcumin
Arm Title
Patients who received placebo
Arm Type
Placebo Comparator
Arm Description
Patients who received placebo
Intervention Type
Drug
Intervention Name(s)
Nanocurcumin
Other Intervention Name(s)
Patients who received nanocurcumin
Intervention Description
Patients will take 80 mg nanocurcumin in the form of capsules daily during the 6 month study period
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Patients who received placebo
Intervention Description
Patients will take placebo in the form of capsules daily during 6 months study period
Primary Outcome Measure Information:
Title
EDSS measurment
Description
EDSS measurment by neurologist
Time Frame
6 months after treatment
Secondary Outcome Measure Information:
Title
Treg cells frequency
Description
Flowcytometry (Treg cells produce anti-inflammatory cytokines)
Time Frame
6 months after treatment
Title
Th17 cells frequency
Description
Flowcytometry (Th17 cells produce inflammatory cytokine and increase inflammation)
Time Frame
6 months after treatment
Title
IL-17 and RORγt expression
Description
qPCR method
Time Frame
6 months after treatment
Title
IL-17 secretion levels
Description
ELISA method
Time Frame
6 months after treatment
Title
microRNAs (miRNA-326) expression
Description
Evaluate the diagnostic value of microRNAs in quantitative polymerase chain reaction (qPCR), in MS patients as compared with healthy control
Time Frame
6 months after treatment
Title
TGF-β and FoxP3 expression
Description
qPCR method
Time Frame
6 months after treatment
Title
TGF-β secretion levels
Description
ELISA method
Time Frame
6 months after treatment
Title
microRNAs (miRNA-106b and miRNA-25) expression
Description
Evaluate the diagnostic value of microRNAs in quantitative polymerase chain reaction
Time Frame
6 months after treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Willingness to cooperate
Aged 18 to 65 years
The diagnosis of Multiple sclerosis by Neurologist
Patients in Relapsing Remitting (RRMS)
Patients with Expanded Disability Status Scale (EDSS) <5/5.
Exclusion Criteria:
Use of nutritional supplements and antioxidant and immunosuppressive drugs 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mehdi Yousefi, Ph.D
Organizational Affiliation
Tabriz University of Medical Scienses
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Hormoz Ayromlou, Neurologist
Organizational Affiliation
Tabriz University of Medical Scienses
Official's Role
Study Chair
Facility Information:
Facility Name
Drug Applied Research Center, Tabriz, Iran
City
Tabriz
Country
Iran, Islamic Republic of
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24096187
Citation
Hoang PD, Cameron MH, Gandevia SC, Lord SR. Neuropsychological, balance, and mobility risk factors for falls in people with multiple sclerosis: a prospective cohort study. Arch Phys Med Rehabil. 2014 Mar;95(3):480-6. doi: 10.1016/j.apmr.2013.09.017. Epub 2013 Oct 3.
Results Reference
background
PubMed Identifier
23363979
Citation
Schneider A, Long SA, Cerosaletti K, Ni CT, Samuels P, Kita M, Buckner JH. In active relapsing-remitting multiple sclerosis, effector T cell resistance to adaptive T(regs) involves IL-6-mediated signaling. Sci Transl Med. 2013 Jan 30;5(170):170ra15. doi: 10.1126/scitranslmed.3004970.
Results Reference
background
PubMed Identifier
23576680
Citation
Schwarz A, Schumacher M, Pfaff D, Schumacher K, Jarius S, Balint B, Wiendl H, Haas J, Wildemann B. Fine-tuning of regulatory T cell function: the role of calcium signals and naive regulatory T cells for regulatory T cell deficiency in multiple sclerosis. J Immunol. 2013 May 15;190(10):4965-70. doi: 10.4049/jimmunol.1203224. Epub 2013 Apr 10.
Results Reference
background
PubMed Identifier
21338381
Citation
Jadidi-Niaragh F, Mirshafiey A. Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scand J Immunol. 2011 Jul;74(1):1-13. doi: 10.1111/j.1365-3083.2011.02536.x.
Results Reference
background
PubMed Identifier
7118227
Citation
Rao TS, Basu N, Siddiqui HH. Anti-inflammatory activity of curcumin analogues. Indian J Med Res. 1982 Apr;75:574-8. No abstract available.
Results Reference
background
PubMed Identifier
22445295
Citation
Lescher J, Paap F, Schultz V, Redenbach L, Scheidt U, Rosewich H, Nessler S, Fuchs E, Gartner J, Bruck W, Junker A. MicroRNA regulation in experimental autoimmune encephalomyelitis in mice and marmosets resembles regulation in human multiple sclerosis lesions. J Neuroimmunol. 2012 May 15;246(1-2):27-33. doi: 10.1016/j.jneuroim.2012.02.012. Epub 2012 Mar 22.
Results Reference
background
PubMed Identifier
22108567
Citation
Martinelli-Boneschi F, Fenoglio C, Brambilla P, Sorosina M, Giacalone G, Esposito F, Serpente M, Cantoni C, Ridolfi E, Rodegher M, Moiola L, Colombo B, De Riz M, Martinelli V, Scarpini E, Comi G, Galimberti D. MicroRNA and mRNA expression profile screening in multiple sclerosis patients to unravel novel pathogenic steps and identify potential biomarkers. Neurosci Lett. 2012 Feb 2;508(1):4-8. doi: 10.1016/j.neulet.2011.11.006. Epub 2011 Nov 7.
Results Reference
background
PubMed Identifier
19838199
Citation
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. Erratum In: Nat Immunol. 2010 Jun;11(6):543.
Results Reference
background
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The Immunomodulatory Effects of Oral Nanocurcumin in Multiple Sclerosis Patients
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