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Multiple SclerosisPhase 3D-Lay-MSNCT01817166

Efficacy of Cholecalciferol (Vitamin D3) for Delaying the Diagnosis of MS After a Clinically Isolated Syndrome

A Phase 3 study testing Vitamin D, Imaging and Lumbar puncture in people with Multiple Sclerosis, run by Centre Hospitalier Universitaire de Nīmes at 33 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The main objective of this study is to evaluate the efficacy and tolerance of 2 years of treatment with cholecalciferol (vitamin D3) in patients with a clinically isolated syndrome at high risk for MS (CIS). Read more about this study

Who is it for?
Ages 18 to 56 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
Vitamin D, Imaging and Lumbar puncture
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
316 participants
Where
33 sitesin 2 countries
Study dates
16 Jul 2013to 4 Jan 2023
Phase
Phase 3
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 56 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • The patient must have given his/her informed and signed consent
  • The patient must be insured or beneficiary of a health insurance plan
  • The patient is available for 24 months of follow-up
  • The patient has had a classic CIS with the past 90 days
  • Reference cerebro-medullary MRI scheduled within the 90 days after the beginning of symptoms
  • With MRI (cerebro ± medullary) showing demyelination according to spatial spread criteria by Swanton (2006):
Show all 12Show fewer
  • At least 1 lesion in at least 2 of the 4 following territories: (1) Peri-ventricular; (2) Juxta-cortical; (3) Sub-tentorial; (4) Medullary
  • No other suspected pathology
  • Vitamin D level in blood less than 100 nmol / l at the pre-inclusion visit
  • Women of childbearing potential must use very effective contraception for the duration of the study. A very effective contraceptive method is defined as a method resulting in a low failure rate (that is to say less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, IUDs, sexual abstinence, or partner with a vasectomy.
  • Randomisation stratification criteria:
  • The patient can also also meet the temporal dissemination criteria defined according to McDonald criteria 2010 (Polman et al., 2011), because this condition is currently not sufficient for prescribing a background treatment: Simultaneous presence of at least one asymptomatic lesion taking on contrast and at least one asymptomatic lesion not taking on contrast after injection of gadolinium

Who cannot join

  • The patient is participating in another study (this criteria does not apply to the POLAR study (RCB 2011-A01269-32); patients included in this study may simultaneously participate in the POLAR study)
  • The patient is in an exclusion period determined by a previous study
  • The patient is under judicial protection, under tutorship or curatorship
  • The patient refuses to sign the consent
  • It is impossible to correctly inform the patient
  • The patient is pregnant, parturient, or breastfeeding
Show all 18Show fewer
  • Major medical or psychiatric illness that, according to the investigator, would result in the patient running an unnecessary risk or that could affect compliance with the study protocol
  • Vitamin D insufficiency linked to currently active digestive or more general diseases (celiac disease, inflammatory bowel disease, intestinal bypass, short bowel syndrome, cirrhosis, nephrotic syndrome, hyperthyroidism, rickets, hypoparathyroidism, cancer, granulomatous diseases and lymphomas)
  • Moderate or severe renal insufficiency (creatinine clearance less than 60 ml / min)
  • Epilepsy not adequately controlled by treatment
  • Any illness requiring chronic treatment with corticosteroids
  • Patient with osteoporosis or history of osteopenia
  • Pathology requiring calcium intakes greater than 1 gram per day
  • Current or past history of hypercalcemia
  • Medications that affect the metabolism of vitamin D other than corticosteroids; e.g. anticonvulsants [phenobarbital, primidone, phenytoin] rifampicin, isoniazid, ketoconazole, 5-FU and leucovorin, thiazide diuretics.
  • Situations accompanied by increased vulnerability to hypercalcemia, e.g. arrhythmia or known heart disease, treatment with digitalis, and subjects with nephrolithiasis.
  • Contraindications to vitamin D3 as mentioned in the documentation for UVEDOSE
  • Known hypersensitivity to gadolinium and / or known inability to undergo an MRI (pacemaker, osteosynthesis material, intraocular metal splinter, etc ....).

Trial locations and contacts

33 sites in 2 countries.

33 sites in 2 countries

France32 sites

  • CHU d'Amiens - Hôpital Nord

    Amiens, 80054

  • CHU de Lyon - Hôpital Pierre Wertheimer

    Bron, 69677

  • CHU de Caen - Hôpital Côte de Nacre

    Caen, 14033

  • CHU de Clermont Ferrand - Hôpital Gabriel-Montpied

    Clermont-Ferrand, 63003

  • CH Sud Francilien

    Corbeil-Essonnes, 91100

  • Clinique des Cèdres - Capio

    Cornebarrieu, 31700

  • CHU de Dijon

    Dijon, 21079

  • CHU de Grenoble - Hôpital A Michallon

    Grenoble, 38043

  • CHRU de Lille - Hôpital Roger Salengro

    Lille, 59037

  • CHU de Limoges - Hôpital Dupuytren

    Limoges, 87042

  • Groupe Hospitalier de l'Institut Catholique de Lille

    Lomme, 59462

  • CHU de Montpellier - Hôpital Gui de Chauliac

    Montpellier, 34295

  • CHU de Nancy - Hôpital Central

    Nancy, 54035

  • CHU de Nantes - Hôtel-Dieu

    Nantes, 44093

  • CHU de Nice - Hôpital Pasteur

    Nice, 06002

  • CHU de Nîmes - Hôpital Universitaire Carémeau

    Nîmes, 30029

  • MAILLART Elisabeth - La Pitié Salpétrière

    Paris, 75013

  • Fondation Ophtalmologique Adolphe Rothschild

    Paris, 75019

  • APHP - Hôpital Saint-Antoine

    Paris, 75571

  • CH de Pau

    Pau, 64000

  • CH de Perpignan - Hôpital Saint Jean

    Perpignan, 66046

  • CH de Cornouaille - Site Quimper - Hôpital Laennec

    Quimper, 29107

  • CHU de Reims - Hôpital Maison Blanche

    Reims, 51092

  • CHU de Rennes - Hôpital PontChaillou

    Rennes, 35033

  • CHU de Rouen - Hôpital Charles Nicolle

    Rouen, 76031

  • CH de Poissy - Saint-Germain-en-Laye

    Saint-Germain-en-Laye, 78100

  • CH de Saumur

    Saumur, 49403

  • CHRU de Strasbourg - Hôpital Civil

    Strasbourg, 67091

  • CHRU de Toulouse - Hôpital Purpan

    Toulouse, 31059

  • CHRU de Tours - Hôpital Bretonneau

    Tours, 37044

  • CH de Versailles - Hôpital Mignot

    Versailles, 78000

  • CH de Vichy - Jacques Larin

    Vichy, 03207

Other trials in France

Martinique1 site

  • CHU de Martinique - Hôpital Pierre Zobda-Quitman

    Fort-de-France, 97200

Other trials in Martinique

About this study

Official title: Multicentric, Randomized, Double-blind Versus Placebo Study Evaluating the Efficacy of Treatment With Cholecalciferol (Vitamin D3) for Delaying the Diagnosis of Multiple Sclerosis (MS) After a Clinically Isolated Syndrome (CIS). Comparison of Conversion Rates After 2 Years.

The main objective of this study is to evaluate the efficacy and tolerance of 2 years of treatment with cholecalciferol (vitamin D3) in patients with a clinically isolated syndrome at high risk for MS (CIS).

Read the detailed description

The secondary objectives of this study are:

  1. evaluate clinical efficacy: delay to conversion; number of relapses/episodes per year B. evaluate efficacy in terms of resonance imaging parameters (cerebral/spinal MRI) C. evaluate efficacy in terms of slowing the progression of disability as measured by EDSS score and subscores D. measure and assess cognitive abilities (PASAT) E. evaluate changes in quality of life (EQ5D questionnaires, SF36, and TLS-TLS-QoL10 COPING10), fatigue questionnaire (FSMC) and anxiety / depression questionnaire (HADS) F. evaluate treatment tolerance G. to correlate changes in clinical and imaging parameters with the evolution of serum levels of 25(OH)D2 and 25(OH)D3 H. establish a biobank of DNA and RNA from all patients in the study and conduct analyses of gene polymorphisms involved in the metabolism of vitamin D and the HLA system based on the increased levels of vitamin D after supplementation I. establish a biobank of CSF, plasma, blood cells, serum and RNA samples for patients in selected centers for research on prognostic biomarkers of conversion J. establish a biobank consisting of plasma tubes collected for the determination of 25-hydroxy-vitamin D K. Estimate the rate of discordance between the conversion decision made by the study neurologist and the result of the MRI re-interpretation performed at the end of the study as well as the proportion of patients identified a posteriori as as erroneously included according to the centralized reading.
Being tested
Vitamin D, Placebo, Imaging, Lumbar puncture, Blood sampling
Keywords
cholecalciferol, vitamin D, immune disease, clinically isolated syndrome
Medical subject headings
Multiple Sclerosis, Immune System Diseases

What participants receive

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

  • Vitamin DDrug

    Also called Cholecalciferol

    Patients will receive 100.000 UI of cholecalciferol every 14 days for a maximum of 24 months or until conversion to full multiple sclerosis has occurred.

  • PlaceboDrug

    Patients will receive a placebo treatment mimicking 100.000 UI of cholecalciferol every 14 days for a maximum of 24 months or until conversion to full multiple sclerosis has occurred.

  • ImagingOther

    Also called Cerebro-medullar MRI

    All patients are scheduled for MRI scans at baseline, 3 months, 12 months, 24 months, as well as upon conversion to full MS.

  • Lumbar punctureBiological

    A baseline collection of cerebral spinal fluid may be required for certain patients (doctor's decision.)

  • Blood samplingBiological

    Blood sampling is required of all patients at baseline, 3 months, 6 months, 12 months, 18 months and 24 months, as well as upon conversion to MS.

  • Urine samplesBiological

    Urine samples are required of all patients at baseline, 3 months, 6 months, 12 months, 18 months, 24 months, and upon conversion to MS.

Study groups in NCT01817166
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPatients in this arm will receive a placebo treatment mimicking 100.000 UI of cholecalciferol every 14 days for a maximum of 24 months or until conversion to full multiple sclerosis has occurred. Intervention: Placebo Intervention: Imaging Intervention: Lumbar puncture Intervention: Blood sampling Intervention: Urine samples
Receives: Drug: Placebo; Other: Imaging; Biological: Lumbar puncture; Biological: Blood sampling; Biological: Urine samples
Vit DExperimentalPatients in this arm will receive 100.000 UI of cholecalciferol every 14 days for a maximum of 24 months or until conversion to full multiple sclerosis has occurred. Intervention: Vitamin D Intervention: Imaging Intervention: Lumbar puncture Intervention: Blood sampling Intervention: Urine samples
Receives: Drug: Vitamin D; Other: Imaging; Biological: Lumbar puncture; Biological: Blood sampling; Biological: Urine samples

What is being measured

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

  1. Conversion to MS yes/no

    Conversion to MS according to criteria described by McDonald (Polman et al 2005)

    Measured: 24 months

Secondary outcomes (75)

  1. Number of relapse episodes (number per year)

    Measured: 24 months

  2. number of new brain lesions found in FLAIR MRI or medullary lesions found in T2 MRI

    Measured: 3 months

  3. number of new brain lesions found in FLAIR MRI or medullary lesions found in T2 MRI

    Measured: 12 months

  4. number of new brain lesions found in FLAIR MRI or medullary lesions found in T2 MRI

    Measured: 24 months

  5. Number of new T1 lesions taking on Gadolinium highlighting

    qualitative variable: 0, 1, or >1

    Measured: 3 months

  6. Number of new T1 lesions taking on Gadolinium highlighting

    qualitative variable: 0, 1, or >1

    Measured: 12 months

  7. Number of new T1 lesions taking on Gadolinium highlighting

    qualitative variable: 0, 1, or >1

    Measured: 24 months

  8. Number of hyposignal T1 lesions (black holes)

    Measured: 3 months

  9. Number of hyposignal T1 lesions (black holes)

    Measured: 12 months

  10. Number of hyposignal T1 lesions (black holes)

    Measured: 24 months

  11. Lesional burden in mm^3 for each cerebral MRI

    Measured: 3 months

  12. Lesional burden in mm^3 for each cerebral MRI

    Measured: 12 months

  13. Lesional burden in mm^3 for each cerebral MRI

    Measured: 24 months

  14. Total number of Gadolinium highlighted lesions on T1 images

    Exact number (semiautomatic measure)

    Measured: 3 months

  15. Total number of Gadolinium highlighted lesions on T1 images

    Exact number (semiautomatic measure)

    Measured: 12 months

  16. Total number of Gadolinium highlighted lesions on T1 images

    Exact number (semiautomatic measure)

    Measured: 24 months

  17. Normalized cerebral volume (SIENAX) obtained from a T13D sequence

    mm^3

    Measured: 3 months

  18. Normalized cerebral volume (SIENAX) obtained from a T13D sequence

    mm^3

    Measured: 12 months

  19. Normalized cerebral volume (SIENAX) obtained from a T13D sequence

    mm^3

    Measured: 24 months

  20. Change in global cerebral volume (mm^3)

    Measured: baseline versus 24 months

  21. EDSS score, including all subscores

    Measured: baseline

  22. EDSS score, including all subscores

    Measured: 3 months

  23. EDSS score, including all subscores

    Measured: 12 months

  24. EDSS score, including all subscores

    Measured: 24 months

  25. EDSS score, including all subscores

    Measured: after second MS episode (1st relapse)(maximum 24 months)

  26. score for the PASAT 3 seconds section of the MSFC score

    Measured: baseline

  27. score for the PASAT 3 seconds section of the MSFC score

    Measured: 3 months

  28. score for the PASAT 3 seconds section of the MSFC score

    Measured: 12 months

  29. score for the PASAT 3 seconds section of the MSFC score

    Measured: 24 months

  30. score for the PASAT 3 seconds section of the MSFC score

    Measured: after second MS episode (1st relapse)(maximum 24 months)

  31. EQ5D questionnaire

    Measured: baseline

  32. EQ5D questionnaire

    Measured: 3 months

  33. EQ5D questionnaire

    Measured: 12 months

  34. EQ5D questionnaire

    Measured: 24 months

  35. SF36 questionnaire

    Measured: baseline

  36. SF36 questionnaire

    Measured: 3 months

  37. SF36 questionnaire

    Measured: 12 months

  38. SF36 questionnaire

    Measured: 24 months

  39. FSMC fatigue scale

    Measured: baseline

  40. FSMC fatigue scale

    Measured: 3 months

  41. FSMC fatigue scale

    Measured: 12 months

  42. FSMC fatigue scale

    Measured: 24 months

  43. TLS-QOL10 questionnaire

    Measured: baseline

  44. TLS-QOL10 questionnaire

    Measured: 3 months

  45. TLS-QOL10 questionnaire

    Measured: 12 months

  46. TLS-QOL10 questionnaire

    Measured: 24 months

  47. TLS-Coping10 questionnaire

    Measured: baseline

  48. TLS-Coping10 questionnaire

    Measured: 3 months

  49. TLS-Coping10 questionnaire

    Measured: 12 months

  50. TLS-Coping10 questionnaire

    Measured: 24 months

  51. HADS questionnaire

    Measured: baseline

  52. HADS questionnaire

    Measured: 3 months

  53. HADS questionnaire

    Measured: 12 months

  54. HADS questionnaire

    Measured: 24 months

  55. Presence/absence of adverse events

    Presence/absence of adverse events the severity of which will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3. Grades I, II, III, IV, V.

    Measured: baseline

  56. Presence/absence of adverse events

    Presence/absence of adverse events the severity of which will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3. Grades I, II, III, IV, V.

    Measured: 3 months

  57. Presence/absence of adverse events

    Presence/absence of adverse events the severity of which will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3. Grades I, II, III, IV, V.

    Measured: 6 months

  58. Presence/absence of adverse events

    Presence/absence of adverse events the severity of which will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3. Grades I, II, III, IV, V.

    Measured: 12 months

  59. Presence/absence of adverse events

    Presence/absence of adverse events the severity of which will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3. Grades I, II, III, IV, V.

    Measured: 18 months

  60. Presence/absence of adverse events

    Presence/absence of adverse events the severity of which will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3. Grades I, II, III, IV, V.

    Measured: 24 months

  61. 25(OH)D2+D3 serum level (nmol/l)

    Measured: baseline

  62. 25(OH)D2+D3 serum level (nmol/l)

    Measured: 3 months

  63. 25(OH)D2+D3 serum level (nmol/l)

    Measured: 6 months

  64. 25(OH)D2+D3 serum level (nmol/l)

    Measured: 12 months

  65. 25(OH)D2+D3 serum level (nmol/l)

    Measured: 18 months

  66. 25(OH)D2+D3 serum level (nmol/l)

    Measured: 24 months

  67. 25(OH)D2+D3 serum level (nmol/l)

    Measured: upon conversion to MS (maximum 24 months)

  68. Calciuria/creatinuria

    Measured: baseline

  69. Calciuria/creatinuria

    Measured: 3 months

  70. Calciuria/creatinuria

    Measured: 6 months

  71. Calciuria/creatinuria

    Measured: 12 months

  72. Calciuria/creatinuria

    Measured: 18 months

  73. Calciuria/creatinuria

    Measured: 24 months

  74. Calciuria/creatinuria

    Measured: upon conversion to MS (maximum 24 months)

  75. Delay until conversion to MS

    The number of days that pass from the beginning of treatment to conversion to MS according to McDonald 2005 criteria (Polman et al 2005)

    Measured: 24 months

Timeline

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

  1. First posted22 Mar 2013 (estimated)
  2. Study start16 Jul 2013
  3. Primary completion4 Jan 2023
  4. Study completion4 Jan 2023

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
316 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01817166
Sponsor's protocol ID
PHRC-N/2012/ET-01
Other IDs
2012-005821-59
Acronym
D-Lay-MS
Status last verified
Jan 2024
First submitted
20 Mar 2013
Last updated
12 Jan 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • Thouvenot E, Laplaud D, Lebrun-Frenay C, Derache N, Le Page E, Maillart E, Froment-Tilikete C, Castelnovo G, Casez O, Coustans M, Guennoc AM, Heinzlef O, Magy L, Nifle C, Ayrignac X, Fromont A, Gaillard N, Caucheteux N, Patry I, De Seze J, Deschamps R, Clavelou P, Biotti D, Edan G, Camu W, Agherbi H, Renard D, Demattei C, Fabbro-Peray P, Mura T, Rival M; D-Lay MS Investigators. High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial. JAMA. 2025 Apr 22;333(16):1413-1422. doi: 10.1001/jama.2025.1604.

    PubMed 40063041

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vitamin D, Imaging and Lumbar puncture in people with Multiple Sclerosis, run by Centre Hospitalier Universitaire de Nīmes at 33 sites in 2 countries.

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 12 inclusion and 18 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 12 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in France, Martinique. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Conversion to MS yes/no (time frame: 24 months). 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 NCT01817166, 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 12 Jan 2024.

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