Multiple SclerosisPhase 2NCT03150966
The Immunomodulatory Effects of Oral Nanocurcumin in Multiple Sclerosis Patients
A Phase 2 study testing Nanocurcumin in people with Multiple Sclerosis, run by Tabriz University of Medical Sciences at 1 site in Iran.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- 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
- 41 participants
- Where
- 1 siteIran
- Study dates
- 8 Jun 2016to 7 Nov 2017
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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 Multiple Sclerosis Patients
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.
.
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- Nanocurcumin, Placebo
- Keywords
- Multiple sclerosis, Nanocurcumin, MicroRNAs, Th17 cells, Treg cells
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NanocurcuminDrug
Also called Patients who received nanocurcumin
Patients will take 80 mg nanocurcumin in the form of capsules daily during the 6 month study period
PlaceboDrug
Also called Patients who received placebo
Patients will take placebo in the form of capsules daily during 6 months study period
| Study group | Role | What they receive |
|---|---|---|
| Patients who received nanocurcumin | Experimental | Patients who received nanocurcumin Receives: Drug: Nanocurcumin |
| Patients who received placebo | Placebo comparator | Patients who received placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
EDSS measurment
EDSS measurment by neurologist
Measured: 6 months after treatment
Secondary outcomes (8)
Treg cells frequency
Flowcytometry (Treg cells produce anti-inflammatory cytokines)
Measured: 6 months after treatment
Th17 cells frequency
Flowcytometry (Th17 cells produce inflammatory cytokine and increase inflammation)
Measured: 6 months after treatment
IL-17 and RORγt expression
qPCR method
Measured: 6 months after treatment
IL-17 secretion levels
ELISA method
Measured: 6 months after treatment
microRNAs (miRNA-326) expression
Evaluate the diagnostic value of microRNAs in quantitative polymerase chain reaction (qPCR), in MS patients as compared with healthy control
Measured: 6 months after treatment
TGF-β and FoxP3 expression
qPCR method
Measured: 6 months after treatment
TGF-β secretion levels
ELISA method
Measured: 6 months after treatment
microRNAs (miRNA-106b and miRNA-25) expression
Evaluate the diagnostic value of microRNAs in quantitative polymerase chain reaction
Measured: 6 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 posted12 May 2017
- Study start8 Jun 2016
- Primary completion10 Aug 2017
- Study completion7 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies 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
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tabriz University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mehdi Yousefi, Ph.D, Study director, Tabriz University of Medical SciensesHormoz Ayromlou, Neurologist, Study chair, Tabriz University of Medical Scienses
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03150966
- Sponsor's protocol ID
- TabrizUMS-Nerve-002
- Status last verified
- May 2017
- First submitted
- 6 May 2017
- Last updated
- 17 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 24096187Schneider 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.
PubMed 23363979Schwarz 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.
PubMed 23576680Jadidi-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.
PubMed 21338381Rao TS, Basu N, Siddiqui HH. Anti-inflammatory activity of curcumin analogues. Indian J Med Res. 1982 Apr;75:574-8. No abstract available.
PubMed 7118227Lescher 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.
PubMed 22445295Martinelli-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.
PubMed 22108567Du 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 Sep 2018. 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 Multiple Sclerosis Patients
- ClinicalTrials.gov ID
- NCT03150966
- Acronym / sponsor ID
- TabrizUMS-Nerve-002
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple sclerosis, Nanocurcumin, MicroRNAs, Th17 cells, Treg cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Tabriz University of Medical SciencesUniversity, hospital or other
- Study start
- 8 Jun 2016 (actual)
- Primary completion
- 10 Aug 2017 (actual)
- Study completion
- 7 Nov 2017 (actual)
- First posted
- 12 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients who received nanocurcumin | Experimental | Drug: NanocurcuminPatients who received nanocurcumin |
| Patients who received placebo | Placebo comparator | Drug: PlaceboPatients who received placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| NanocurcuminAlso: Patients who received nanocurcuminPatients will take 80 mg nanocurcumin in the form of capsules daily during the 6 month study period | Drug | Patients who received nanocurcumin |
| PlaceboAlso: Patients who received placeboPatients will take placebo in the form of capsules daily during 6 months study period | Drug | Patients who received placebo |
Primary outcome
EDSS measurment
Time frame: 6 months after treatment
EDSS measurment by neurologist
8 secondary outcomes
Treg cells frequency
Time frame: 6 months after treatment
Th17 cells frequency
Time frame: 6 months after treatment
IL-17 and RORγt expression
Time frame: 6 months after treatment
IL-17 secretion levels
Time frame: 6 months after treatment
microRNAs (miRNA-326) expression
Time frame: 6 months after treatment
TGF-β and FoxP3 expression
Time frame: 6 months after treatment
TGF-β secretion levels
Time frame: 6 months after treatment
microRNAs (miRNA-106b and miRNA-25) expression
Time frame: 6 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 Sep 2018.
- Background: PubMed 24096187Hoang 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.
- Background: PubMed 23363979Schneider 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.
- Background: PubMed 23576680Schwarz 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.
- Background: PubMed 21338381Jadidi-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.
- 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 22445295Lescher 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.
- Background: PubMed 22108567Martinelli-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.
- 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
Tabriz University of Medical Scienses
Hormoz Ayromlou, Neurologist study chair
Tabriz University of Medical Scienses
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 Multiple Sclerosis, 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 Sep 2018. 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?
EDSS measurment (time frame: 6 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 NCT03150966, which also lists 8 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 Sep 2018.