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

• Register: ClinicalTrials.gov
• Last refreshed on: 22 January 2024
• Main ID: NCT01817166
• Date of registration: 20/03/2013
• Prospective Registration: Yes
• Primary sponsor: Centre Hospitalier Universitaire de Nimes
• Public title: Efficacy of Cholecalciferol (Vitamin D3) for Delaying the Diagnosis of MS After a Clinically Isolated Syndrome D-Lay-MS
• Scientific 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.
• Date of first enrolment: July 16, 2013
• Target sample size: 316
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT01817166
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

France, Martinique

Contacts

• Name: Eric Thouvenot, MD, PhD
• Affiliation: Centre Hospitalier Universitaire de Nîmes

• Name: Eric Thouvennot, MD, PhD
• Affiliation: Centre Hospitalier Universitaire de Nîmes

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- 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

Exclusion Criteria:

- 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

- 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 ....).



Age minimum: 18 Years
Age maximum: 56 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Biological: Urine samples

Drug: Vitamin D

Drug: Placebo

Biological: Blood sampling

Biological: Lumbar puncture

Other: Imaging

Primary Outcome(s)

Conversion to MS yes/no [Time Frame: 24 months]

Secondary Outcome(s)

25(OH)D2+D3 serum level (nmol/l) [Time Frame: 12 months]

25(OH)D2+D3 serum level (nmol/l) [Time Frame: 18 months]

Calciuria/creatinuria [Time Frame: 24 months]

FSMC fatigue scale [Time Frame: 24 months]

Normalized cerebral volume (SIENAX) obtained from a T13D sequence [Time Frame: 3 months]

Presence/absence of adverse events [Time Frame: 3 months]

25(OH)D2+D3 serum level (nmol/l) [Time Frame: baseline]

FSMC fatigue scale [Time Frame: 3 months]

HADS questionnaire [Time Frame: 24 months]

Number of new T1 lesions taking on Gadolinium highlighting [Time Frame: 24 months]

Number of relapse episodes (number per year) [Time Frame: 24 months]

Presence/absence of adverse events [Time Frame: baseline]

SF36 questionnaire [Time Frame: 12 months]

Total number of Gadolinium highlighted lesions on T1 images [Time Frame: 24 months]

TLS-QOL10 questionnaire [Time Frame: 12 months]

Delay until conversion to MS [Time Frame: 24 months]

EDSS score, including all subscores [Time Frame: 24 months]

Calciuria/creatinuria [Time Frame: 12 months]

Calciuria/creatinuria [Time Frame: 6 months]

EQ5D questionnaire [Time Frame: 24 months]

EQ5D questionnaire [Time Frame: 3 months]

Change in global cerebral volume (mm^3) [Time Frame: baseline versus 24 months]

EDSS score, including all subscores [Time Frame: baseline]

Number of hyposignal T1 lesions (black holes) [Time Frame: 12 months]

score for the PASAT 3 seconds section of the MSFC score [Time Frame: 24 months]

EDSS score, including all subscores [Time Frame: after second MS episode (1st relapse)(maximum 24 months)]

Lesional burden in mm^3 for each cerebral MRI [Time Frame: 24 months]

Calciuria/creatinuria [Time Frame: 18 months]

Calciuria/creatinuria [Time Frame: baseline]

EDSS score, including all subscores [Time Frame: 12 months]

EDSS score, including all subscores [Time Frame: 3 months]

25(OH)D2+D3 serum level (nmol/l) [Time Frame: 3 months]

25(OH)D2+D3 serum level (nmol/l) [Time Frame: upon conversion to MS (maximum 24 months)]

score for the PASAT 3 seconds section of the MSFC score [Time Frame: 3 months]

score for the PASAT 3 seconds section of the MSFC score [Time Frame: after second MS episode (1st relapse)(maximum 24 months)]

HADS questionnaire [Time Frame: baseline]

Lesional burden in mm^3 for each cerebral MRI [Time Frame: 3 months]

FSMC fatigue scale [Time Frame: 12 months]

HADS questionnaire [Time Frame: 12 months]

EQ5D questionnaire [Time Frame: 12 months]

Lesional burden in mm^3 for each cerebral MRI [Time Frame: 12 months]

Number of new T1 lesions taking on Gadolinium highlighting [Time Frame: 12 months]

Presence/absence of adverse events [Time Frame: 18 months]

TLS-Coping10 questionnaire [Time Frame: 24 months]

TLS-QOL10 questionnaire [Time Frame: baseline]

Normalized cerebral volume (SIENAX) obtained from a T13D sequence [Time Frame: 24 months]

TLS-Coping10 questionnaire [Time Frame: baseline]

Normalized cerebral volume (SIENAX) obtained from a T13D sequence [Time Frame: 12 months]

number of new brain lesions found in FLAIR MRI or medullary lesions found in T2 MRI [Time Frame: 12 months]

Total number of Gadolinium highlighted lesions on T1 images [Time Frame: 12 months]

SF36 questionnaire [Time Frame: 24 months]

SF36 questionnaire [Time Frame: 3 months]

TLS-QOL10 questionnaire [Time Frame: 24 months]

Number of hyposignal T1 lesions (black holes) [Time Frame: 24 months]

number of new brain lesions found in FLAIR MRI or medullary lesions found in T2 MRI [Time Frame: 24 months]

Number of new T1 lesions taking on Gadolinium highlighting [Time Frame: 3 months]

score for the PASAT 3 seconds section of the MSFC score [Time Frame: 12 months]

TLS-Coping10 questionnaire [Time Frame: 12 months]

TLS-QOL10 questionnaire [Time Frame: 3 months]

TLS-Coping10 questionnaire [Time Frame: 3 months]

25(OH)D2+D3 serum level (nmol/l) [Time Frame: 24 months]

25(OH)D2+D3 serum level (nmol/l) [Time Frame: 6 months]

Calciuria/creatinuria [Time Frame: 3 months]

Calciuria/creatinuria [Time Frame: upon conversion to MS (maximum 24 months)]

EQ5D questionnaire [Time Frame: baseline]

FSMC fatigue scale [Time Frame: baseline]

HADS questionnaire [Time Frame: 3 months]

Number of hyposignal T1 lesions (black holes) [Time Frame: 3 months]

number of new brain lesions found in FLAIR MRI or medullary lesions found in T2 MRI [Time Frame: 3 months]

Presence/absence of adverse events [Time Frame: 24 months]

Presence/absence of adverse events [Time Frame: 12 months]

Presence/absence of adverse events [Time Frame: 6 months]

SF36 questionnaire [Time Frame: baseline]

Total number of Gadolinium highlighted lesions on T1 images [Time Frame: 3 months]

score for the PASAT 3 seconds section of the MSFC score [Time Frame: baseline]

Secondary ID(s)

PHRC-N/2012/ET-01

2012-005821-59

Source(s) of Monetary Support

Please refer to primary and secondary sponsors