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

NCT01817166 | Completed Phase 3 DMC

• 2 other identifiers: PHRC-N/2012/ET-012012-005821-59
• Study Type: interventional
• Target: 316
• Locations: 2 countries
• Sites: 33

Brief 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).

Conditions

Multiple Sclerosis

Keywords

cholecalciferol; vitamin D; immune disease; clinically isolated syndrome

Outcome Measures

Primary Outcomes (1)

• Conversion to MS yes/no

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

  24 months

Secondary Outcomes (75)

• Number of relapse episodes (number per year)

  24 months

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

  3 months

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

  12 months

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

  24 months

• Number of new T1 lesions taking on Gadolinium highlighting

  3 months

Other Outcomes (71)

• DNA sample (blood sample) for biobank

  baseline

• Hemogram

  baseline

• Hemogram

  3 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients 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

Drug: Placebo; Other: Imaging; Biological: Lumbar puncture; Biological: Blood sampling; Biological: Urine samples

Vit D

EXPERIMENTAL

Patients 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

Drug: Vitamin D; Other: Imaging; Biological: Lumbar puncture; Biological: Blood sampling; Biological: Urine samples

Interventions

Vitamin D DRUG

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.

Also known as: Cholecalciferol

Vit D

Placebo DRUG

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.

Placebo

Imaging OTHER

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

Also known as: Cerebro-medullar MRI

Placebo; Vit D

Lumbar puncture BIOLOGICAL

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

Placebo; Vit D

Blood sampling BIOLOGICAL

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.

Placebo; Vit D

Urine samples BIOLOGICAL

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

Placebo; Vit D

Eligibility Criteria

• Age: 18 Years - 56 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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):
• 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
• 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

You may not qualify if:

• 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 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
• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (33)

CHU d'Amiens - Hôpital Nord

Amiens, 80054, France

Location

CHU de Lyon - Hôpital Pierre Wertheimer

Bron, 69677, France

Location

CHU de Caen - Hôpital Côte de Nacre

Caen, 14033, France

Location

CHU de Clermont Ferrand - Hôpital Gabriel-Montpied

Clermont-Ferrand, 63003, France

Location

CH Sud Francilien

Corbeil-Essonnes, 91100, France

Location

Clinique des Cèdres - Capio

Cornebarrieu, 31700, France

Location

CHU de Dijon

Dijon, 21079, France

Location

CHU de Grenoble - Hôpital A Michallon

Grenoble, 38043, France

Location

CHRU de Lille - Hôpital Roger Salengro

Lille, 59037, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, 87042, France

Location

Groupe Hospitalier de l'Institut Catholique de Lille

Lomme, 59462, France

Location

CHU de Montpellier - Hôpital Gui de Chauliac

Montpellier, 34295, France

Location

CHU de Nancy - Hôpital Central

Nancy, 54035, France

Location

CHU de Nantes - Hôtel-Dieu

Nantes, 44093, France

Location

CHU de Nice - Hôpital Pasteur

Nice, 06002, France

Location

CHU de Nîmes - Hôpital Universitaire Carémeau

Nîmes, 30029, France

Location

MAILLART Elisabeth - La Pitié Salpétrière

Paris, 75013, France

Location

Fondation Ophtalmologique Adolphe Rothschild

Paris, 75019, France

Location

APHP - Hôpital Saint-Antoine

Paris, 75571, France

Location

CH de Pau

Pau, 64000, France

Location

CH de Perpignan - Hôpital Saint Jean

Perpignan, 66046, France

Location

CH de Cornouaille - Site Quimper - Hôpital Laennec

Quimper, 29107, France

Location

CHU de Reims - Hôpital Maison Blanche

Reims, 51092, France

Location

CHU de Rennes - Hôpital PontChaillou

Rennes, 35033, France

Location

CHU de Rouen - Hôpital Charles Nicolle

Rouen, 76031, France

Location

CH de Poissy - Saint-Germain-en-Laye

Saint-Germain-en-Laye, 78100, France

Location

CH de Saumur

Saumur, 49403, France

Location

CHRU de Strasbourg - Hôpital Civil

Strasbourg, 67091, France

Location

CHRU de Toulouse - Hôpital Purpan

Toulouse, 31059, France

Location

CHRU de Tours - Hôpital Bretonneau

Tours, 37044, France

Location

CH de Versailles - Hôpital Mignot

Versailles, 78000, France

Location

CH de Vichy - Jacques Larin

Vichy, 03207, France

Location

CHU de Martinique - Hôpital Pierre Zobda-Quitman

Fort-de-France, 97200, Martinique

Location

Related Publications (1)

• 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.

  PMID: 40063041 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Immune System Diseases

Interventions

Vitamin D; Cholecalciferol; X-Rays; Spinal Puncture; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Eric Thouvennot, MD, PhD

  Centre Hospitalier Universitaire de Nîmes

  STUDY DIRECTOR

• Eric Thouvenot, MD, PhD

  Centre Hospitalier Universitaire de Nîmes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2013
• First Posted: March 22, 2013
• Study Start: July 16, 2013
• Primary Completion: January 4, 2023
• Study Completion: January 4, 2023
• Last Updated: January 12, 2024

Record last verified: 2024-01

Locations

FR (32); MA (1)