The Immunomodulatory Effects of Oral Nanocurcumin in Multiple Sclerosis Patients

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03150966
• Other study ID #: TabrizUMS-Nerve-002
• Status: Completed
• Phase: Phase 2
• Start date: June 8, 2016
• Est. completion date: November 7, 2017

Study information

• Verified date: May 2017
• Source: Tabriz University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: November 7, 2017
• Est. primary completion date: August 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Nanocurcumin
Patients will take 80 mg nanocurcumin in the form of capsules daily during the 6 month study period
• Placebo
Patients will take placebo in the form of capsules daily during 6 months study period

Locations

Country	Name	City	State
Iran, Islamic Republic of	Drug Applied Research Center, Tabriz, Iran	Tabriz

Sponsors (1)

Lead Sponsor	Collaborator
Tabriz University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

References & Publications (8)

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. — View 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. — View 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. Review. — View Citation

Lescher J, Paap F, Schultz V, Redenbach L, Scheidt U, Rosewich H, Nessler S, Fuchs E, Gärtner J, Brück 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. — View 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. — View Citation

Rao TS, Basu N, Siddiqui HH. Anti-inflammatory activity of curcumin analogues. Indian J Med Res. 1982 Apr;75:574-8. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	EDSS measurment	EDSS measurment by neurologist	6 months after treatment
Secondary	Treg cells frequency	Flowcytometry (Treg cells produce anti-inflammatory cytokines)	6 months after treatment
Secondary	Th17 cells frequency	Flowcytometry (Th17 cells produce inflammatory cytokine and increase inflammation)	6 months after treatment
Secondary	IL-17 and ROR?t expression	qPCR method	6 months after treatment
Secondary	IL-17 secretion levels	ELISA method	6 months after treatment
Secondary	microRNAs (miRNA-326) expression	Evaluate the diagnostic value of microRNAs in quantitative polymerase chain reaction (qPCR), in MS patients as compared with healthy control	6 months after treatment
Secondary	TGF-ß and FoxP3 expression	qPCR method	6 months after treatment
Secondary	TGF-ß secretion levels	ELISA method	6 months after treatment
Secondary	microRNAs (miRNA-106b and miRNA-25) expression	Evaluate the diagnostic value of microRNAs in quantitative polymerase chain reaction	6 months after treatment