Clinical trial NCT03610139: Longitudinal Effect of Vitamin D3 Replacement on Cognitive Performance and MRI Markers in Multiple Sclerosis Patients
Official title: Longitudinal Effect of Vitamin D3 Replacement on Cognitive Performance and MRI Markers in Multiple Sclerosis Patients: A Single-Blind Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Clinically Isolated Syndrome
Clinically Isolated Syndrome, CNS Demyelinating
Vitamin D3 Deficiency
Keywords: cognitive performance
vitamin D3 replacement
Lebanon
Lead sponsor: American University of Beirut Medical Center
Sponsor class: OTHER
First posted: 2018-08-01
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This is a longitudinal single blind randomized trial to test the effects of high compared to low dose vitamin D3 supplementation on cognitive performance at 6 and 12 months, and MRI measures of 12 months duration. A cognitive assessment battery will be administered at baseline, 6 and 12 months. Related clinical data and information on depression and anxiety, lifestyle, and food sources of vitamin D and sun exposure among other variables will also be collected.

Detailed description: Background: Multiple Sclerosis is strongly associated with low serum 25 hydroxy-vitamin-D (25(OH)D) and impaired cognitive performance. In our previous research, participants with low serum 25OHD levels showed significant improvements in visuo-spatial memory delayed recall after 3 months of vitamin D3 supplementation. In addition, serum 25(OH)D was significantly associated with this memory function at baseline and at 3 months. Therefore, the aim of this proposed study is 1) to evaluate the long-term effects 6 and 12 months of high (50,000 IU weekly then 10,000 IU weekly) compared to low dose (800 IU daily) vitamin D3 replacement on cognitive function in MS, and 2) to correlate it with the MRI brain measurements of the hippocampus and the frontal cortex volumes, as well as brain parenchymal fraction, and cerebellum. The investigators will then explore these MRI measures in MS patients with deficient 25(OH)D levels at baseline and at 12 months, and correlate it with their cognitive performance.

Methods: This is a longitudinal single blind randomized trial to test the effects of high compared to low dose vitamin D3 supplementation on cognitive performance at 6 and 12 months, and MRI measures of 12 months duration. A cognitive assessment battery, comprised of the Montreal Cognitive Assessment (only at baseline), Stroop, Symbol Digit Modalities Test, Brief Visual Memory Test, and Verbal Memory Test in Arabic, will be administered at baseline, 6 and 12 months. Related clinical data and information on depression and anxiety, lifestyle, and food sources of vitamin D and sun exposure among other variables will also be collected.

Expected results: MS patients with serum 25(OH)D deficiency who receive high dose vitamin D3 supplementation will demonstrate decreased cognitive impairment at 6 and 12 months post supplementation when compared to those who received low vitamin D3 dose and to their pre-supplementation status. The MRI findings are expected to be associated with cognitive performance at baseline, and serum 25(OH)D levels at baseline, and 12 months.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent form
* Males/ Females
* Age ≥ 18 years old
* Have a definite diagnosis of RRMS as per the revised McDonald 2010 or CIS.
* Untreated or on any MS therapy
* Showed no clinical evidence of relapses during the past month and disease duration not greater than 10 years.
* Subjects who have a serum vitamin D level below 25 ng/ml

Exclusion Criteria:

* All subjects using drugs associated with hypercalcemia.
* Pregnant and with history of primary hyper PTH.
* Subjects with hypercalcemia, renal dysfunction, malignancy, or granulomatous disease, dementia, traumatic brain injury, diagnosis of epilepsy or history of seizure, psychiatric disease other than anxiety and depression, or are found to be suicidal on screening, or taking psychoactive medications other than antidepressants
* Subjects who have a serum vitamin D level above 25 ng/ml
* Subjects who have not done an MRI scan up to 3 months before or after the baseline visit.
* Subjects who have a history of kidney stones
* Subjects with malabsorption
* Individuals with history of alcohol abuse/dependence and/or substance use/abuse/dependence will also be excluded from the study. Men who consume more than 15 drinks per week and women who consume more than eight drinks per week will be considered excessive alcohol consumers and will be excluded from the study.

Primary outcomes:
measure: Change from Baseline Brief Visuospatial Memory Test-Revised (BVMT-R) scores at 6 months
timeFrame: 6 months
measure: Change from Baseline Arabic Verbal Memory Test (VMAT) scores at 6 months
timeFrame: 6 months
measure: Change from Baseline Symbol Digit Modalities Test (SDMT) scores at 6 months
timeFrame: 6 months
measure: Change from Baseline Stroop test scores at 6 months
timeFrame: 6 months
measure: Change from Baseline Brief Visuospatial Memory Test-Revised (BVMT-R) scores at 12 months
timeFrame: 12 months
measure: Change from Baseline Arabic Verbal Memory Test (VMAT) scores at 12 months
timeFrame: 12 months
measure: Change from Baseline Symbol Digit Modalities Test (SDMT) scores at 12 months
timeFrame: 12 months
measure: Change from Baseline Stroop test scores at 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Change from Baseline Magnetic Resonance Imaging Brain Markers of the Hippocampus volume at 12 months
timeFrame: 12 months
measure: Change from Baseline Magnetic Resonance Imaging Brain Markers of the frontal cortex volume at 12 months
timeFrame: 12 months
measure: Change from Baseline Magnetic Resonance Imaging Brain Markers of the brain parenchymal fraction at 12 months
timeFrame: 12 months
measure: Change from Baseline Magnetic Resonance Imaging Brain Markers of the Cerebellum at 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: Beirut
country: Lebanon
facility: Nehme & Therese Tohme Multiple Sclerosis Center
Study officials:
affiliation: American University of Beirut Medical Center
name: Hala Darwish, PhD, RN
role: PRINCIPAL_INVESTIGATOR
References:
citation: Darwish H, Haddad R, Osman S, Ghassan S, Yamout B, Tamim H, Khoury S. Effect of Vitamin D Replacement on Cognition in Multiple Sclerosis Patients. Sci Rep. 2017 Apr 4;7:45926. doi: 10.1038/srep45926.
citation: Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology. 2012 Sep 25;79(13):1397-405. doi: 10.1212/WNL.0b013e31826c197f.
citation: Darwish H, Zeinoun P, Ghusn H, Khoury B, Tamim H, Khoury SJ. Serum 25-hydroxyvitamin D predicts cognitive performance in adults. Neuropsychiatr Dis Treat. 2015 Aug 25;11:2217-23. doi: 10.2147/NDT.S87014. eCollection 2015.
citation: van der Schaft J, Koek HL, Dijkstra E, Verhaar HJ, van der Schouw YT, Emmelot-Vonk MH. The association between vitamin D and cognition: a systematic review. Ageing Res Rev. 2013 Sep;12(4):1013-23. doi: 10.1016/j.arr.2013.05.004. Epub 2013 May 29.