Effect of Vitamin D Replacement on Immune Function and Cognition in MS Patients

NCT01952483 | Completed

• 1 other identifier: IM.SK1.04
• Study Type: observational
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

Assessing the immune activation in MS patients deficient in Vitamin D and whether Vitamin D supplementation reverse the immune activation Evaluating whether Vitamin D deficiency result in lower cognitive performance in MS patients and the effect of Vitamin D supplementation on reversing the cognitive impairment?

Conditions

Multiple Sclerosis (MS)

Keywords

Multiple Sclerosis (MS)

Outcome Measures

Primary Outcomes (1)

• Is there evidence of immune activation in MS patients deficient in Vitamin D and does Vitamin D supplementation reverse the immune activation?

  We will compare the immune responses in patients with Vitamin D deficiency (serum level \<20ng/ml) to those of patients with normal Vitamin D (serum level \>35 µg/ml). We will focus on proliferation and cytokine production to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) peptides and on the percentage of Th1 (IFN gamma producing cells) and Th17 (IL-17 producing cells) during in vitro polarization assays. Our hypothesis is that patients with low Vitamin D have increase proliferation to MBP and MOG and increased production of pro-inflammatory cytokines (IFN gamma and IL-17) and that Vitamin D supplementation will decrease this pro-inflammatory profile.

  3months

Secondary Outcomes (1)

• Does Vitamin D deficiency result in lower cognitive performance in MS patients and does Vitamin D supplementation reverse the cognitive impairment?

  3 months

Study Arms (2)

vitamin D deficient,

Vitamin D deficiency (serum level \<20ng/ml)

Vitamin D normal

Serum level \>35 ng/ml

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Group 1: low vitamin D (less than 25 ng/ml) Group 2: normal vitamin D level (greater than 35 ng/ ml)

You may qualify if:

• Definite diagnosis of Multiple Sclerosis following the revised McDonald MS diagnostic criteria
• Male and Female Aged 18 and above
• On interferon-β treatment (Rebif®, Avonex®, or Betaseron®)
• No signs of active inflammation or attack or new lesions on MRI

You may not qualify if:

• Treatment with immune modulating/ suppressive drugs other than IFN-b within 6 weeks prior to enrolment
• Pregnancy
• Hypercalcemia
• eglomerular filtration rate\<60
• History of primary hyperparathyroidism, hypercalcemia, renal dysfunction, cardiac disease, malignancy, or granulomatous disease
• The occurrence of an exacerbation (defined as an episode of neurologic dysfunction lasting at least 24 hours) within 4 weeks of enrollment
• History of dementia or related disorders
• History of traumatic brain injury
• Diagnosis of epilepsy or history of seizure
• Diagnosis of psychiatric disease, substance abuse/dependence, alcohol abuse/dependence
• Currently, on any of the following medications Lithium, or Thiazide diuretics

Sponsors & Collaborators

• American University of Beirut Medical Center: lead

Study Sites (1)

AUBMC Multiple Sclerosis Center

Beirut, Riad El Solh, 11-0236, Lebanon

Location

Related Publications (5)

• Khoo AL, Joosten I, Michels M, Woestenenk R, Preijers F, He XH, Netea MG, van der Ven AJ, Koenen HJ. 1,25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells. Immunology. 2011 Dec;134(4):459-68. doi: 10.1111/j.1365-2567.2011.03507.x.

  PMID: 22044285 BACKGROUND

• Zivadinov R, Sepcic J, Nasuelli D, De Masi R, Bragadin LM, Tommasi MA, Zambito-Marsala S, Moretti R, Bratina A, Ukmar M, Pozzi-Mucelli RS, Grop A, Cazzato G, Zorzon M. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2001 Jun;70(6):773-80. doi: 10.1136/jnnp.70.6.773.

  PMID: 11385012 BACKGROUND

• Adorini L, Penna G, Giarratana N, Roncari A, Amuchastegui S, Daniel KC, Uskokovic M. Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):437-41. doi: 10.1016/j.jsbmb.2004.03.013.

  PMID: 15225816 BACKGROUND

• Przybelski RJ, Binkley NC. Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function. Arch Biochem Biophys. 2007 Apr 15;460(2):202-5. doi: 10.1016/j.abb.2006.12.018. Epub 2007 Jan 8.

  PMID: 17258168 BACKGROUND

• Barake M, Daher RT, Salti I, Cortas NK, Al-Shaar L, Habib RH, Fuleihan Gel-H. 25-hydroxyvitamin D assay variations and impact on clinical decision making. J Clin Endocrinol Metab. 2012 Mar;97(3):835-43. doi: 10.1210/jc.2011-2584. Epub 2012 Jan 11.

  PMID: 22238386 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

We will focus on proliferation and cytokine production to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) peptides and on the percentage of Th1 (IFN gamma producing cells) and Th17 (IL-17 producing cells) during in vitro polarization assays

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Samia J Khoury, professor

  AUBMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: September 30, 2013
• Study Start: August 1, 2012
• Primary Completion: May 1, 2017
• Study Completion: June 30, 2017
• Last Updated: January 11, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)