Relapsing Remitting Multiple SclerosisPhase 4NCT01225289
Impact of Vitamin A Supplementation on Immune System in Multiple Sclerosis Patients
A Phase 4 study testing Vitamin A in people with Relapsing Remitting Multiple Sclerosis, run by Tehran University of Medical Sciences at 2 sites in Iran.
Trial summary
The aim of this study is to study the comparison between the effects of supplementation with 25000 IU preformed vitamin A (retinyl palmitate) or placebo for 6 months on immune system and Th1/Th2 balance in patients with Multiple Sclerosis. Read more about this study
- Who is it for?
- Ages 20 to 45 years
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis
- What is being tested?
- Vitamin A
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 2 sitesIran
- Study dates
- Oct 2009to Jan 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients who have used interferon beta in last 3 months. Patients with 1-5 EDSS
Who cannot join
- Patients who have diseases which affect on Th1/Th2 balance such as asthma, active viral infections, and autoimmune diseases, OR
- Patients who have allergy to vitamin A compounds, OR
- Patients who have used vitamin supplements in last 3 months.
Trial locations and contacts
2 sites in 1 country.
Iran2 sites
Tehran University of Medical Sciences, School of Public Health Tehran, Tehran, Iran, Islamic Republic o
Tehran, Tehran Province
Tehran University of Medical Sciences, School of Public Health
Tehran, Tehran Province
About this study
Official title: The Study of the Effects of Vitamin A Supplementation on Immune System and Th1/Th2 Balance in Patients With Multiple Sclerosis
The aim of this study is to study the comparison between the effects of supplementation with 25000 IU preformed vitamin A (retinyl palmitate) or placebo for 6 months on immune system and Th1/Th2 balance in patients with Multiple Sclerosis.
Read the detailed description
Multiple Sclerosis (MS) is a chronic inflammatory disease where Th1 like responses from myelin-specific CD4+ T cells, as secretion of pro-inflammatory IFN-g, are believed to play a major role in the pathogenesis. The myelin-specific T cells that mediate tissue destruction in MS are believed to become activated outside the central nervous system (CNS) in lymphoid tissue and when they cross the blood brain barrier they will re-encounter their antigen. Immune deviation is the redirection of the immune response from most often Th1 like responses to Th2 like responses, even though the opposite can also occur. Vitamin A (VA) or VA-like analogs known as retinoids, are potent hormonal modifiers of type 1 or type 2 responses but a definitive description of their mechanism(s) of action is lacking. High level dietary vitamin A enhances Th2 cytokine production and IgA responses, and is likely to decrease Th1 cytokine production. Retinoic acid inhibits IL 12 production in activated macrophages, and RA pretreatment of macrophages reduces IFNγ production and increases IL4 production in antigen primed CD4 T cells. Supplemental treatment with vitamin A or retinoic acid (RA) decreases IFNγ and increases IL5, IL10, and IL4 production. Thus, vitamin A deficiency biases the immune response in a Th1 direction, whereas high level dietary vitamin A may bias the response in a Th2 direction.
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Being tested
- Vitamin A, Placebo
- Keywords
- Multiple Sclerosis, Vitamin A, CD4-Positive T-Lymphocytes, Th1 Cells, Th2 Cells
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin ADietary supplement
Also called Retinyl palmitate
25000 IU/day (one capsule per day) Vitamin A for 6 months
PlaceboDrug
1 capsule per day for six months
| Study group | Role | What they receive |
|---|---|---|
| with Multiple Sclerosis/ vitamin A | Active comparator | Patients with MS confirmed Relapsing Remitting Type who receive 25000 IU/day vitamin A Receives: Dietary Supplement: Vitamin A |
| with Multiple Sclerosis/ placebo | Placebo comparator | Patients with Multiple Sclerosis confirmed Relapsing Remitting Type who receive 1 cap of placebo per day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference Serum Levels of High-sensitive C-reactive Protein (Hs-CRP), Before and After of Supplementation
Measured: first day and after 6 month
Secondary outcomes (3)
Difference of IL-4 Levels in Supernatant of Peripheral Blood Mononucleated Cells (PBMCs) Stimulated With Phytohemagglutinin (PHA), Before and After of Supplementation
Measured: first day and after 6 month
Difference of Retinol Binding Protein (RBP) / Transthyretin (TTR) Ratio, (Difference of RBP/ TTR Ratio), Before and After of Supplementation
Measured: first day and after 6 month
Peripheral Blood Mononucleated Cells (PBMCs) Proliferation Assay (BrdU Colorimetric)
difference of PBMCs proliferation stimulated with myelin oligodendrocyte glycoprotein (MOG), before and after of supplementation
Measured: first day and after 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2010 (estimated)
- Study startOct 2009
- Primary completionDec 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsing Remitting 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tehran University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ali Akbar Saboor Yaraghi, Tehran University of Medical Sciences
- Investigators
- Ali Akbar Saboor Yaraghi, PhD, Principal investigator, Tehran University of Medical SciencesSima Jafarirad, PhD student, Principal investigator, Tehran University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01225289
- Sponsor's protocol ID
- 88-03-27-9576
- Status last verified
- Feb 2014
- First submitted
- 6 Sep 2010
- Last updated
- 14 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Mohammadzadeh Honarvar N, Harirchian MH, Koohdani F, Siassi F, Abdolahi M, Bitarafan S, Salehi E, Sahraian MA, Eshraghian MR, Saboor-Yarghi AA. The effect of vitamin A supplementation on retinoic acid-related orphan receptor gammat (RORgammat) and interleukin-17 (IL-17) gene expression in Avonex-treated multiple sclerotic patients. J Mol Neurosci. 2013 Nov;51(3):749-53. doi: 10.1007/s12031-013-0058-9. Epub 2013 Jul 19.
PubMed 23868508
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Study of the Effects of Vitamin A Supplementation on Immune System and Th1/Th2 Balance in Patients With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01225289
- Acronym / sponsor ID
- 88-03-27-9576
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Vitamin A, CD4-Positive T-Lymphocytes, Th1 Cells, Th2 Cells
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Tehran University of Medical SciencesUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 21 Oct 2010 (estimated)
- Results
- Posted 14 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to study the comparison between the effects of supplementation with 25000 IU preformed vitamin A (retinyl palmitate) or placebo for 6 months on immune system and Th1/Th2 balance in patients with Multiple Sclerosis.
Detailed description
Multiple Sclerosis (MS) is a chronic inflammatory disease where Th1 like responses from myelin-specific CD4+ T cells, as secretion of pro-inflammatory IFN-g, are believed to play a major role in the pathogenesis. The myelin-specific T cells that mediate tissue destruction in MS are believed to become activated outside the central nervous system (CNS) in lymphoid tissue and when they cross the blood brain barrier they will re-encounter their antigen. Immune deviation is the redirection of the immune response from most often Th1 like responses to Th2 like responses, even though the opposite can also occur. Vitamin A (VA) or VA-like analogs known as retinoids, are potent hormonal modifiers of type 1 or type 2 responses but a definitive description of their mechanism(s) of action is lacking. High level dietary vitamin A enhances Th2 cytokine production and IgA responses, and is likely to decrease Th1 cytokine production. Retinoic acid inhibits IL 12 production in activated macrophages, and RA pretreatment of macrophages reduces IFNγ production and increases IL4 production in antigen primed CD4 T cells. Supplemental treatment with vitamin A or retinoic acid (RA) decreases IFNγ and increases IL5, IL10, and IL4 production. Thus, vitamin A deficiency biases the immune response in a Th1 direction, whereas high level dietary vitamin A may bias the response in a Th2 direction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| with Multiple Sclerosis/ vitamin A | Active comparator | Dietary Supplement: Vitamin APatients with MS confirmed Relapsing Remitting Type who receive 25000 IU/day vitamin A |
| with Multiple Sclerosis/ placebo | Placebo comparator | Drug: PlaceboPatients with Multiple Sclerosis confirmed Relapsing Remitting Type who receive 1 cap of placebo per day |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Patients who have used interferon beta in last 3 months. Patients with 1-5 EDSS
Key exclusion criteria (3 listed)
- Patients who have diseases which affect on Th1/Th2 balance such as asthma, active viral infections, and autoimmune diseases, OR
- Patients who have allergy to vitamin A compounds, OR
- Patients who have used vitamin supplements in last 3 months.
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 |
|---|---|---|
| Vitamin AAlso: Retinyl palmitate25000 IU/day (one capsule per day) Vitamin A for 6 months | Dietary supplement | with Multiple Sclerosis/ vitamin A |
| Placebo1 capsule per day for six months | Drug | with Multiple Sclerosis/ placebo |
Primary outcome
Difference Serum Levels of High-sensitive C-reactive Protein (Hs-CRP), Before and After of Supplementation
Time frame: first day and after 6 month
3 secondary outcomes
Difference of IL-4 Levels in Supernatant of Peripheral Blood Mononucleated Cells (PBMCs) Stimulated With Phytohemagglutinin (PHA), Before and After of Supplementation
Time frame: first day and after 6 month
Difference of Retinol Binding Protein (RBP) / Transthyretin (TTR) Ratio, (Difference of RBP/ TTR Ratio), Before and After of Supplementation
Time frame: first day and after 6 month
Peripheral Blood Mononucleated Cells (PBMCs) Proliferation Assay (BrdU Colorimetric)
Time frame: first day and after 6 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23868508Mohammadzadeh Honarvar N, Harirchian MH, Koohdani F, Siassi F, Abdolahi M, Bitarafan S, Salehi E, Sahraian MA, Eshraghian MR, Saboor-Yarghi AA. The effect of vitamin A supplementation on retinoic acid-related orphan receptor gammat (RORgammat) and interleukin-17 (IL-17) gene expression in Avonex-treated multiple sclerotic patients. J Mol Neurosci. 2013 Nov;51(3):749-53. doi: 10.1007/s12031-013-0058-9. Epub 2013 Jul 19.
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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.
Ali Akbar Saboor Yaraghi, PhD principal investigator
Tehran University of Medical Sciences
Sima Jafarirad, PhD student principal investigator
Tehran University of Medical Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vitamin A in people with Relapsing Remitting Multiple Sclerosis, run by Tehran University of Medical Sciences at 2 sites 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 1 inclusion and 3 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 14 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Difference Serum Levels of High-sensitive C-reactive Protein (Hs-CRP), Before and After of Supplementation (time frame: first day and after 6 month). 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 NCT01225289, which also lists 1 linked publication.
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 14 Mar 2014.