AzTrials
AzTrials

Multiple SclerosisPhase 2NCT02096133

Vitamin D3 and the Stress-axis in MS

A Phase 2 study testing Cholecalciferol in people with Multiple Sclerosis, run by Academic MS Center Limburg at 2 sites in Netherlands.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Patients with multiple sclerosis (MS) have an increased risk of developing a major depression. The investigators observed a protective effect of high vitamin D levels on the risk of depression in MS. This might be driven by the effect of vitamin D on the stress-axis. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Multiple Sclerosis
What is being tested?
Cholecalciferol
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
54 participants
Where
2 sitesNetherlands
Study dates
13 Oct 2014to 7 Nov 2016
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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female
  • Relapsing Remitting MS
  • At start of study > 6 weeks in clinical remission of disease
  • Age > 18 years.
  • Premenopausal
  • Treated with either no immune-modulating treatment, or the currently registered MS modulating treatments: Interferon beta 1a (Rebif®), Interferon Beta 1b (Betaferon® or Avonex®), Glatiramer Acetate (Copaxone®), dimethylfumarate (Tecfidera®), teriflunomide (Aubagio®)) or fingolimod (Gilenya®).

Who cannot join

  • Any contraindication to vitamin D according to Summary of Product Characteristics: Hypercalcaemia, hypervitaminosis D, nephrolithiasis, diseases or conditions resulting in hypercalcaemia and/or hypercalciuria (incl. primary hyperparathyroidism), severe renal impairment .
  • Use of dexamethasone or other systemic glucocorticosteroids <2 months prior to first study visit
  • Supplementation of >=1000 IU/d (25µg) vitamin D2 or D3
  • Medical history of disturbed vitamin D/ calcium metabolism other than low intake
  • Present clinical (major)depression
  • Present treatment with anti-depressants, benzodiazepines, or neuroleptics.
  • Treatment with high-dose dexamethasone for MS exacerbation during study.
  • Pregnancy or the intention to become pregnant during the study period.

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

  • Canisius Wilhelmina Ziekenhuis

    Nijmegen

  • Academic MS Center Limburg, Orbis Medical Center

    Sittard-Geleen, 6162 BG

Other trials in Netherlands

About this study

Official title: Regulation of the Stress-axis by Vitamin D3 in Subjects With Multiple Sclerosis; a Double-blinded, Randomized, Placebo-controlled Study

Patients with multiple sclerosis (MS) have an increased risk of developing a major depression. The investigators observed a protective effect of high vitamin D levels on the risk of depression in MS. This might be driven by the effect of vitamin D on the stress-axis. Therefore, the main goal of the present study is to assess whether high dose vitamin D supplementation results in a suppression of the stress-axis, as measured by decreased levels of cortisol.

Read the detailed description

The lifetime incidence of a major depression in Multiple Sclerosis (MS) is 50%. (Patten et al. Neurology 2003; 61(11):1524-7) Our group reported a negative correlation between vitamin D status and depression score of the Hospital Anxiety and Depression Scale (HADS) in a cross-sectional dataset of Dutch MS patients. (Knippenberg et al. Acta Neurol Scand 2011; 124(3):171-5) This suggests an interaction between vitamin D and biological mechanisms affecting susceptibility to depression. Currently, we have two main hypotheses: 1) Vitamin D regulates the hypothalamic stress axis in MS. Based on our findings that cortisol releasing hormone (CRH)-positive hypothalamic neurons in the brains of MS patients stained positive for the vitamin D receptor (VDR) and 1,25(OH)2D-24-hydroxylase (24-OHase). (smolders et al. J Neuropathol Exp Neurol 2013;72(2):91-105) 2) Vitamin D affects T cell cytokine profile and hereby the odds of developing depression. Also in non-MS depressed patients increased levels of pro-inflammatory cytokines are detected (Maes et al. Metab Brain Dis 2009; 24: 27-53). Vitamin D3 has shown to be a potent promotor of T cell regulation both in vitro and in vivo. (Smolders et al. J Neuroimmunol 2008;194:7-17 and Smolders et al. PLoS One 2010;5:e15235) The main goal of this study is to assess whether supplementation of high doses vitamin D3 results in a suppression of saliva cortisol day-curves in subjects with multiple sclerosis, and we will explore whether the pro-inflammatory cytokine profile of T lymphocytes is regulated.

Being tested
Cholecalciferol, Placebo comparator
Keywords
Multiple sclerosis, vitamin D, HPA-axis, cortisol
Medical subject headings
Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CholecalciferolDrug

    Also called Vigantol Oil

    Vitamin D3 solution

  • Placebo comparatorOther

    Placebo comparator

Study groups in NCT02096133
Study groupRoleWhat they receive
CholecalciferolExperimentalPatients receive 1dd 100ug vitamin D3 (drops) for 16 weeks
Receives: Drug: Cholecalciferol
Placebo comparatorPlacebo comparatorplacebo drops during 16 weeks
Receives: Other: Placebo comparator

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The area under the curve (AUC) of the cortisol day curve

    This number is constructed by combining the saliva cortisol levels at awakening, 11:00, 15:00, 20:00, and 22:00 hours (5 time-points).

    Measured: At baseline and after 16 weeks of supplementation.

Secondary outcomes (5)

  1. The slope of the cortisol day-curve

    The slope of the day-curve is the slope of the decrease of saliva cortisol measured throughout the cortisol day curve

    Measured: At baseline and after 16 weeks of supplementation

  2. The cortisol awakening response

    The awakening response is described by the rise in saliva cortisol from awakening to 60 minutes after awakening with respectively measurements at awakening, 15 minutes, 30 minutes, 45 minutes and 60 minutes (5 time-points).

    Measured: At baseline and after 16 weeks of supplementation

  3. Clinical outcomes on depression

    The clinical outcomes on depression will be measured by the depression sub-score of HADS and the FSSS fatigue score.

    Measured: At baseline and after 16 weeks of supplementation

  4. Efficacy of supplementation

    To measure efficacy 25(OH)D levels will be measured.

    Measured: At baseline and after 16 weeks of supplementation. Side effects will also be checked at 8 weeks of supplementation.

  5. Side effects

    Side effects will be measured after 8 and 16 weeks of treatment. Serum levels of calcium, albumin and creatinine will be determined, as well as calcium and creatinine levels in urine.

    Measured: At baseline, after 8 and after 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2014 (estimated)
  2. Study start13 Oct 2014
  3. Primary completion7 Nov 2016
  4. Study completion7 Nov 2016

Why it stopped: difficulties with inclusion

Resources

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
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02096133
Sponsor's protocol ID
EMR200109_635
Other IDs
2014-000728-97, 2014
Status last verified
Jan 2017
First submitted
21 Mar 2014
Last updated
25 Jan 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Rolf L, Damoiseaux J, Huitinga I, Kimenai D, van den Ouweland J, Hupperts R, Smolders J. Stress-Axis Regulation by Vitamin D3 in Multiple Sclerosis. Front Neurol. 2018 Apr 26;9:263. doi: 10.3389/fneur.2018.00263. eCollection 2018.

    PubMed 29755397

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cholecalciferol in people with Multiple Sclerosis, run by Academic MS Center Limburg at 2 sites in Netherlands.

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 6 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: stopped early, as of the sponsor's last update on 25 Jan 2017. 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 Netherlands. 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 was stopped early (reason given: difficulties with inclusion). Results are not available in the source record.

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 area under the curve (AUC) of the cortisol day curve (time frame: At baseline and after 16 weeks of supplementation.). 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 NCT02096133, 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 25 Jan 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in