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

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?

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis (MS)

Detailed Description

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 ng/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.

We will measure cognitive performance in patients with Vitamin D deficiency (serum level <20ng/ml) compared to those of patients with normal Vitamin D (serum level >35 ng/ml) after adjusting for educational levels and disease duration. We hypothesize that low Vitamin D has a negative effect on cognitive performance and that Vitamin D supplementation will improve cognitive function.

• Study Type: Observational
• Enrollment (Actual): 108

Contacts and Locations

Study Locations

• Lebanon
  • Riad El Solh
    • Beirut, Riad El Solh, Lebanon, 11-0236
      • AUBMC Multiple Sclerosis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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)

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
vitamin D deficient,; Vitamin D deficiency (serum level <20ng/ml)
Vitamin D normal; Serum level >35 ng/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Does Vitamin D deficiency result in lower cognitive performance in MS patients and does Vitamin D supplementation reverse the cognitive impairment?	We will measure cognitive performance in patients with Vitamin D deficiency (serum level <20ng/ml) compared to those of patients with normal Vitamin D (serum level >35 ng/ml) after adjusting for educational levels and disease duration. We hypothesize that low Vitamin D has a negative effect on cognitive performance and that Vitamin D supplementation will improve cognitive function.	3 months

Collaborators and Investigators

• Sponsor: American University of Beirut Medical Center
• Investigators: Principal Investigator: Samia J Khoury, professor, AUBMC

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: September 19, 2013
• First Submitted That Met QC Criteria: September 25, 2013
• First Posted (Estimate): September 30, 2013

Study Record Updates

• Last Update Posted (Actual): January 11, 2018
• Last Update Submitted That Met QC Criteria: January 10, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Multiple Sclerosis (MS)
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: IM.SK1.04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO