Clinically Isolated SyndromePhase 1/2CISAVIDNCT01728922
Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome
A Phase 1/2 study testing 5000IU vitamin D and 10000IU vitamin D in people with Clinically Isolated Syndrome and Multiple Sclerosis, run by University College Dublin at 1 site in Ireland.
Trial summary
The primary purpose of this study is to assess the immune response to vitamin D supplementation at two doses (5,000 IU and 10,000 IU daily) in both healthy controls and patients with clinically isolated syndrome compared to placebo. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Clinically Isolated Syndrome, Multiple Sclerosis
- What is being tested?
- 5000IU vitamin D and 10000IU vitamin D
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteIreland
- Study dates
- 6 Nov 2012to 5 Jun 2016
- Phase
- Phase 1/2
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
None listed.
Who cannot join
- Patients in whom any disease other than demyelination could explain their signs and symptoms.
- Participants with known disease of the parathyroids, a history of vitamin D intolerance, sarcoidosis, a history of hypercalcaemia of any cause.
- Participants with a baseline abnormality in serum urea, creatinine, calcium, parathormone.
- Participants on thiazide diuretics (hypercalcaemia risk).
- Patients with occurrence of a relapse less than six weeks prior to entry to study.
- Previous treatment with beta-interferons or glatiramer acetate or steroids in the last three months.
- Any previous treatment with mitoxantrone or other immunosuppressant.
- Participants already taking supplemental vitamin D.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome and Healthy Control Participants. An Exploratory Double Blind Placebo Randomised Controlled Study.
The primary purpose of this study is to assess the immune response to vitamin D supplementation at two doses (5,000 IU and 10,000 IU daily) in both healthy controls and patients with clinically isolated syndrome compared to placebo. Secondary endpoints include (1) disease outcome in the clinically isolated syndrome in terms of clinical relapses and evidence of new lesions on MRI (McDonald's MS), 2) Safety of doses used
Read the detailed description
Primary endpoint: To determine the effects of vitamin D supplementation at two doses a) 5,000 IU daily b) 10,000 IU daily compared to c) placebo a 24 weeks period on the change from baseline in frequency of CD4 T cell subsets and cytokine responses by peripheral blood mononuclear cells in 1) patients with the clinically isolated syndrome. 2) healthy control participants.
Secondary endpoints:
- To determine whether there is a dose response effect of supplementation using 5,000 IU and 10,000 IU of vitamin D versus placebo over 24 weeks on the change from baseline in the frequency of CD4 T cell subsets and cytokine responses by PBMC in 1) patients with the clinically isolated syndrome (CIS) 2) healthy control participants
- To establish whether there is a clinical response to vitamin D measured by a) change in the number of T2 lesions and Gadolinium enhancing lesions on MRI scanning at 24 weeks compared to baseline b) reduction in relapses over 24 weeks in treated (both 5,000 IU and 10,000 IU) CIS patients versus CIS patients receiving placebo.
- Conditions
- Clinically Isolated Syndrome, Multiple Sclerosis
- Being tested
- 5000IU vitamin D, 10000IU vitamin D, Placebo
- Keywords
- Clinically isolated syndrome, Multiple sclerosis, Vitamin D, Immune response, CD4 T cell subsets, Cytokine
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5000IU vitamin DDietary supplement
Also called Vigantol Oil
Vigantol Oil
10000IU vitamin DDietary supplement
Also called Vigantol Oil
Vigantol Oil
PlaceboOther
Also called Placebo Oil
Placebo Oil
| Study group | Role | What they receive |
|---|---|---|
| Healthy control - 5,000 IU vitamin D | Active comparator | 13 healthy controls will be administered 5,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed. Receives: Dietary Supplement: 5000IU vitamin D |
| Healthy control - 10,000 IU vitamin D | Active comparator | 13 healthy controls will be administered 10,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed. Receives: Dietary Supplement: 10000IU vitamin D |
| CIS - placebo | Placebo comparator | 15 patients will be administered placebo and all outcome measures will be assessed. Receives: Other: Placebo |
| CIS - 5,000 IU vitamin D | Active comparator | 15 patients will be administered 5,000 IU vitamin D and all outcomes will be assessed. Receives: Dietary Supplement: 5000IU vitamin D |
| CIS - 10,000 IU vitamin D | Active comparator | 15 patients will be administered 10,000 IU of vitamin D and all outcome measures assessed. Receives: Dietary Supplement: 10000IU vitamin D |
| Healthy control - placebo | Placebo comparator | 13 control participants who will be administered placebo. These will be assessed for the primary outcome and safety outcomes only. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effects of two doses of vitamin D and placebo therapy on the change in the frequency of CD4 T cell subsets and cytokine responses of PBMC over 24 weeks of therapy from baseline.
A number of measures will be examined in particular IL-10 production and the frequency of Th17 cells.
Measured: This outcome measure will be assessed at baseline and at 24 weeks.
Secondary outcomes (3)
The number of new T2 and gadolinium enhancing lesions compared to baseline amongst the study group.
The MRI out-come measure will assess the a) number of Gadolinium enhancing lesions b) the number of new and enlarging T2 lesions c) the combined unique lesion count (new and enlarging T2 lesions plus Gadolinium enhancing lesions) after 24 weeks of therapy in the three arms, 5000IU, 10,000IU vitamin D and placebo . Mean and median new T2 and gadolinium-enhancing lesions at 24 weeks (end of the trial) will be compared for each treatment allocation group. In addition the mean and median number of new T2 lesions plus gadolinium enhancing lesions in all the CIS patients on vitamin D will be compared to the mean and median in the placebo group.
Measured: Baseline and 24 weeks
Relapse occurrence in the CIS patients during 24 weeks of the trial
Relapse occurrence in the CIS patients during 24 weeks of the trial;(i) annualised relapse rates (ARR), (ii) percentage of patients free from relapses and (iii) time to first relapse will be compared for each treatment allocation group. In addition the same relapse measures will be applied to both vitamin D treated groups combined and compared to those in the placebo group.
Measured: At each clinic visit or as the need arises.
The percentage of CIS patients in each treatment arm free from any evidence of disease activity (No relapses, no new T2 lesions, no gadolinium enhancing lesions).
Measured: At 24 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2012 (estimated)
- Study start6 Nov 2012
- Primary completion5 Jun 2015
- Study completion5 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clinically Isolated SyndromeStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double-blind, dose ranging, two doses of vitamin D, randomised parallel groups with placebo arms in clinically isolated syndrome and heathy control participants
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College Dublin
- Sponsor type
- University, hospital or other
- Collaborators
- University of Dublin, Trinity College, St Vincent's University Hospital, Ireland
- Responsible party
- Principal investigator, Professor Michael Hutchinson, University College Dublin
- Investigators
- Michael Hutchinson, MB, FRCP, Principal investigator, St Vincent's University Hospital, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01728922
- Sponsor's protocol ID
- 2012CIS/VD/SVUH
- Acronym
- CISAVID
- Status last verified
- May 2017
- First submitted
- 8 Nov 2012
- Last updated
- 3 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all demographic details and outcome measures may be obtained directly from the PI by e-mail
Publications
O'Connell K, Kelly S, Kinsella K, Jordan S, Kenny O, Murphy D, Heffernan E, O'Laoide R, O'Shea D, McKenna C, Cassidy L, Fletcher J, Walsh C, Brady J, McGuigan C, Tubridy N, Hutchinson M. Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: study protocol for an exploratory randomized double- blind placebo-controlled trial. Trials. 2013 Aug 27;14:272. doi: 10.1186/1745-6215-14-272.
PubMed 23981773
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome and Healthy Control Participants. An Exploratory Double Blind Placebo Randomised Controlled Study.
- ClinicalTrials.gov ID
- NCT01728922
- Acronym / sponsor ID
- CISAVID / 2012CIS/VD/SVUH
- Conditions
- Clinically Isolated Syndrome, Multiple Sclerosis
- Keywords
- Clinically isolated syndrome, Multiple sclerosis, Vitamin D, Immune response, CD4 T cell subsets, Cytokine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- University College DublinUniversity, hospital or other
- Collaborators
- University of Dublin, Trinity College, St Vincent's University Hospital, Ireland
- Study start
- 6 Nov 2012 (actual)
- Primary completion
- 5 Jun 2015 (actual)
- Study completion
- 5 Jun 2016 (actual)
- First posted
- 20 Nov 2012 (estimated)
- 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.
The primary purpose of this study is to assess the immune response to vitamin D supplementation at two doses (5,000 IU and 10,000 IU daily) in both healthy controls and patients with clinically isolated syndrome compared to placebo. Secondary endpoints include (1) disease outcome in the clinically isolated syndrome in terms of clinical relapses and evidence of new lesions on MRI (McDonald's MS), 2) Safety of doses used
Detailed description
Primary endpoint: To determine the effects of vitamin D supplementation at two doses a) 5,000 IU daily b) 10,000 IU daily compared to c) placebo a 24 weeks period on the change from baseline in frequency of CD4 T cell subsets and cytokine responses by peripheral blood mononuclear cells in 1) patients with the clinically isolated syndrome. 2) healthy control participants.
Secondary endpoints:
- To determine whether there is a dose response effect of supplementation using 5,000 IU and 10,000 IU of vitamin D versus placebo over 24 weeks on the change from baseline in the frequency of CD4 T cell subsets and cytokine responses by PBMC in 1) patients with the clinically isolated syndrome (CIS) 2) healthy control participants
- To establish whether there is a clinical response to vitamin D measured by a) change in the number of T2 lesions and Gadolinium enhancing lesions on MRI scanning at 24 weeks compared to baseline b) reduction in relapses over 24 weeks in treated (both 5,000 IU and 10,000 IU) CIS patients versus CIS patients receiving placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- double-blind, dose ranging, two doses of vitamin D, randomised parallel groups with placebo arms in clinically isolated syndrome and heathy control participants
| Arm | Type | Receives |
|---|---|---|
| Healthy control - 5,000 IU vitamin D | Active comparator | Dietary Supplement: 5000IU vitamin D13 healthy controls will be administered 5,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed. |
| Healthy control - 10,000 IU vitamin D | Active comparator | Dietary Supplement: 10000IU vitamin D13 healthy controls will be administered 10,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed. |
| CIS - placebo | Placebo comparator | Other: Placebo15 patients will be administered placebo and all outcome measures will be assessed. |
| CIS - 5,000 IU vitamin D | Active comparator | Dietary Supplement: 5000IU vitamin D15 patients will be administered 5,000 IU vitamin D and all outcomes will be assessed. |
| CIS - 10,000 IU vitamin D | Active comparator | Dietary Supplement: 10000IU vitamin D15 patients will be administered 10,000 IU of vitamin D and all outcome measures assessed. |
| Healthy control - placebo | Placebo comparator | Other: Placebo13 control participants who will be administered placebo. These will be assessed for the primary outcome and safety outcomes only. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (8 listed)
- Patients in whom any disease other than demyelination could explain their signs and symptoms.
- Participants with known disease of the parathyroids, a history of vitamin D intolerance, sarcoidosis, a history of hypercalcaemia of any cause.
- Participants with a baseline abnormality in serum urea, creatinine, calcium, parathormone.
- Participants on thiazide diuretics (hypercalcaemia risk).
- Patients with occurrence of a relapse less than six weeks prior to entry to study.
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 |
|---|---|---|
| 5000IU vitamin DAlso: Vigantol OilVigantol Oil | Dietary supplement | CIS - 5,000 IU vitamin D, Healthy control - 5,000 IU vitamin D |
| 10000IU vitamin DAlso: Vigantol OilVigantol Oil | Dietary supplement | CIS - 10,000 IU vitamin D, Healthy control - 10,000 IU vitamin D |
| PlaceboAlso: Placebo OilPlacebo Oil | Other | CIS - placebo, Healthy control - placebo |
Primary outcome
The effects of two doses of vitamin D and placebo therapy on the change in the frequency of CD4 T cell subsets and cytokine responses of PBMC over 24 weeks of therapy from baseline.
Time frame: This outcome measure will be assessed at baseline and at 24 weeks.
A number of measures will be examined in particular IL-10 production and the frequency of Th17 cells.
3 secondary outcomes
The number of new T2 and gadolinium enhancing lesions compared to baseline amongst the study group.
Time frame: Baseline and 24 weeks
Relapse occurrence in the CIS patients during 24 weeks of the trial
Time frame: At each clinic visit or as the need arises.
The percentage of CIS patients in each treatment arm free from any evidence of disease activity (No relapses, no new T2 lesions, no gadolinium enhancing lesions).
Time frame: At 24 weeks.
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 3 May 2017.
- Derived from this study: PubMed 23981773O'Connell K, Kelly S, Kinsella K, Jordan S, Kenny O, Murphy D, Heffernan E, O'Laoide R, O'Shea D, McKenna C, Cassidy L, Fletcher J, Walsh C, Brady J, McGuigan C, Tubridy N, Hutchinson M. Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: study protocol for an exploratory randomized double- blind placebo-controlled trial. Trials. 2013 Aug 27;14:272. doi: 10.1186/1745-6215-14-272.
- Individual participant dataSharing planned: Yes. all demographic details and outcome measures may be obtained directly from the PI by e-mail
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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.
Michael Hutchinson, MB, FRCP principal investigator
St Vincent's University Hospital, Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 5000IU vitamin D and 10000IU vitamin D in people with Clinically Isolated Syndrome and Multiple Sclerosis, run by University College Dublin at 1 site in Ireland.
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 0 inclusion and 8 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 3 May 2017. 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 Ireland. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The effects of two doses of vitamin D and placebo therapy on the change in the frequency of CD4 T cell subsets and cytokine responses of PBMC over 24 weeks of therapy from baseline. (time frame: This outcome measure will be assessed at baseline and at 24 weeks.). 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 NCT01728922, 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 3 May 2017.