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

Multiple Sclerosis (MS) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01952483
• Other study ID #: IM.SK1.04
• Status: Completed
• Phase: N/A
• First received: September 19, 2013
• Last updated: January 10, 2018
• Start date: August 2012
• Est. completion date: June 30, 2017

Study information

• Verified date: January 2018
• Source: American University of Beirut Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: June 30, 2017
• Est. primary completion date: May 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-ß 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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis (MS)
• Sclerosis

Locations

Country	Name	City	State
Lebanon	AUBMC Multiple Sclerosis Center	Beirut	Riad El Solh

Sponsors (1)

Lead Sponsor	Collaborator
American University of Beirut Medical Center

Country where clinical trial is conducted

Lebanon, 

References & Publications (5)

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 Jan 8. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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