Longitudinal Effect of Vitamin D3 Replacement on Cognitive Performance and MRI Markers in Multiple Sclerosis Patients

NCT03610139 | Unknown DMC

• 1 other identifier: BIO-2017-0395
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (8)

• Change from Baseline Brief Visuospatial Memory Test-Revised (BVMT-R) scores at 6 months

  It is a visuospatial memory test that is comprised of three memory trials (10 seconds each) followed by delayed recall trial after 25 minutes. It has been widely used as a quick measure of memory at bedside and in MS patients. The minimum score on each trial is 0 and the maximum score on each trial is 12. Higher values represent a better outcome.

  6 months

• Change from Baseline Arabic Verbal Memory Test (VMAT) scores at 6 months

  It is a verbal memory test. It consists of 45 words that are distributed among 3 lists (List A, List B, and a Recognition List). Lists A and B are each composed of 15 words belonging to 3 semantic categories: vegetables, animals, and stationary. The recognition list is composed 45 words that include homonyms, shared or related words and unrelated words with respect to the previous two lists. The VMAT is administered as follows: List A Immediate Free Recall (5 trials) - List B Immediate Free Recall Trial - List A Short Delay Free Recall Trial - List A Short Delay Cued Recall Trial - List A Long Delay Free Recall Trial - List A Long Delay Cued Recall Trial. After 25 minutes of the last trial, List A Delayed Recognition Trial is administered. For each trial, the minimum total score is 0 and the maximum total score is 15. Higher scores represent a better outcome. For each trial except the recognition trial, repeated and intrusive words are counted separately.

  6 months

• Change from Baseline Symbol Digit Modalities Test (SDMT) scores at 6 months

  It is a known and widely used speed of processing test. Oral SDMT will be administered; it does not require translation and has been used in Lebanon before. It consists of one trial. The minimum total score is 0 and the maximum total score is 110. Higher scores represent a better outcome.

  6 months

• Change from Baseline Stroop test scores at 6 months

  It is a highly established test of attention. Subject is given a list of colors in black ink to read (Stroop 1), then a list of colors in their corresponding ink color (Stroop 2), and then finally a list of colors with incongruent ink colors (Stroop 3), the participant is expected to read the word without being affected by interfering mismatching color. The number of words read in a minute (minus the errors) is the dependent measure and interference will be calculated using the following equation: Interference = Stroop 3 - \[(Stroop 1+Stroop 2)/2\]. For each of the 3 lists, the minimum total score is 0 and the maximum total score is 100. Higher scores represent a better outcome. For the interference, the minimum score is -100 and the maximum score is 0. Higher scores represent a better outcome.

  6 months

• Change from Baseline Brief Visuospatial Memory Test-Revised (BVMT-R) scores at 12 months

  It is a visuospatial memory test that is comprised of three memory trials (10 seconds each) followed by delayed recall trial after 25 minutes. It has been widely used as a quick measure of memory at bedside and in MS patients. The minimum score on each trial is 0 and the maximum score on each trial is 12. Higher values represent a better outcome.

  12 months

• Change from Baseline Arabic Verbal Memory Test (VMAT) scores at 12 months

  It is a verbal memory test. It consists of 45 words that are distributed among 3 lists (List A, List B, and a Recognition List). Lists A and B are each composed of 15 words belonging to 3 semantic categories: vegetables, animals, and stationary. The recognition list is composed 45 words that include homonyms, shared or related words and unrelated words with respect to the previous two lists. The VMAT is administered as follows: List A Immediate Free Recall (5 trials) - List B Immediate Free Recall Trial - List A Short Delay Free Recall Trial - List A Short Delay Cued Recall Trial - List A Long Delay Free Recall Trial - List A Long Delay Cued Recall Trial. After 25 minutes of the last trial, List A Delayed Recognition Trial is administered. For each trial, the minimum total score is 0 and the maximum total score is 15. Higher scores represent a better outcome. For each trial except the recognition trial, repeated and intrusive words are counted separately.

  12 months

• Change from Baseline Symbol Digit Modalities Test (SDMT) scores at 12 months

  It is a known and widely used speed of processing test. Oral SDMT will be administered; it does not require translation and has been used in Lebanon before. It consists of one trial. The minimum total score is 0 and the maximum total score is 110. Higher scores represent a better outcome.

  12 months

• Change from Baseline Stroop test scores at 12 months

  It is a highly established test of attention. Subject is given a list of colors in black ink to read (Stroop 1), then a list of colors in their corresponding ink color (Stroop 2), and then finally a list of colors with incongruent ink colors (Stroop 3), the participant is expected to read the word without being affected by interfering mismatching color. The number of words read in a minute (minus the errors) is the dependent measure and interference will be calculated using the following equation: Interference = Stroop 3 - \[(Stroop 1+Stroop 2)/2\]. For each of the 3 lists, the minimum total score is 0 and the maximum total score is 100. Higher scores represent a better outcome. For the interference, the minimum score is -100 and the maximum score is 0. Higher scores represent a better outcome.

  12 months

Secondary Outcomes (4)

• Change from Baseline Magnetic Resonance Imaging Brain Markers of the Hippocampus volume at 12 months

  12 months

• Change from Baseline Magnetic Resonance Imaging Brain Markers of the frontal cortex volume at 12 months

  12 months

• Change from Baseline Magnetic Resonance Imaging Brain Markers of the brain parenchymal fraction at 12 months

  12 months

• Change from Baseline Magnetic Resonance Imaging Brain Markers of the Cerebellum at 12 months

  12 months

Study Arms (2)

low dose vitamin D3 supplementation

ACTIVE COMPARATOR

Patients in this group will take 800 IU daily dose of vitamin D supplementation. They will be kept on 800 IU for 6 months. If they still had low vitamin D at 3 months, they will be asked about their adherence to the supplement, the investigators will remind them to take it as prescribed, and the investigators will keep the 800 IU vitamin D supplement dose for another 3 months. If they were still deficient at 6 months, the investigators will switch them to 10,000 IU weekly dose.

Dietary Supplement: Vitamin D3

high dose vitamin D3 supplementation

EXPERIMENTAL

Patients in this group will take 50,000 IU weekly dose of vitamin D supplementation. Patients who will reach normal serum vitamin D level, between 40-80 ng/ml, at 3 or 6 months will be asked to decrease their Vitamin D3 supplementation as follows: Those who will reach levels between 40-60ng/ml will be switched to 10,000 IU three times per week, and those who reach levels between 60-80 ng/ml will be switched to 10,000 IU once weekly. If they did not have any improvement in their levels of vitamin D at 3 or 6 months, they will be asked about their adherence to the supplement and the investigators will remind them to take it as prescribed and the investigators will keep them at the 50,000 IU weekly dose.

Dietary Supplement: Vitamin D3

Interventions

Vitamin D3 DIETARY_SUPPLEMENT

At baseline, patients with deficient 25(OH)D levels will be randomly assigned 1:1 to receive either the high dose or standard dose vitamin D supplementation.

high dose vitamin D3 supplementation; low dose vitamin D3 supplementation

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• American University of Beirut Medical Center: lead

Study Sites (1)

Nehme & Therese Tohme Multiple Sclerosis Center

Beirut, 1107 2020, Lebanon

RECRUITING

Related Publications (4)

• 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.

  PMID: 28374837 BACKGROUND

• 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.

  PMID: 23008220 BACKGROUND

• 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.

  PMID: 26346368 BACKGROUND

• 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.

  PMID: 23727408 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Demyelinating Diseases

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Hala Darwish, PhD, RN

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hala Darwish, PhD, RN

CONTACT

+961-1-350000; hd30@aub.edu.lb

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: One of the co-investigators who will perform the MRI segmentation and analysis will be blind to the participants' treatment allocation. Research assistants who will administer the cognitive tests to all participants will be blind to the participants' treatment allocation.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor - Hariri School of Nursing / Managing Director - Abu-Haidar Neuroscience Institute / Managing Director - Nehme and Therese Tohme Multiple Sclerosis Center

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: August 1, 2018
• Study Start: May 21, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: August 30, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)