High-Dose Vitamin D Supplements in Older Adults
This Phase II study will test high-dose oral vitamin D compared to a standard dose for treating vitamin D insufficiency in a diverse group of older adults. The effects of the different doses on cognitive function will also be assessed to gather data for a potential future trial in older adults at risk for dementia.
|Minimum Age||Maximum Age||Gender||Healthy Volunteers|
|65 Years||90 Years||All||Yes|
- Low vitamin D status, as measured at screening
- Fluent in English or Spanish
- Willingness to be randomized to high-dose or standard dose vitamin D
- Education-adjusted scores between 12 to 30 on the Montreal Cognitive Assessment
- Diagnosis of no cognitive impairment, mild cognitive impairment, or mild Alzheimer's disease, as determined by cognitive and memory tests
- Alzheimer's medications, such as donepezil and memantine, are allowed if doses have been stable for more than 6 weeks, and no changes are anticipated; experimental Alzheimer's therapies, such as anti-amyloid or anti-tau treatments, will be excluded.
- Lacks adequate vision, hearing, or literacy to complete psychometric tests
- Liver insufficiency, defined by either albumin less than 3.3 g/dL or by a value more than 2 times the upper limit of normal (ULN) in either alanine aminotransaminase or bilirubin, or more than 3 times the ULN for aspartate aminotransaminase
- Kidney insufficiency, defined by either serum creatinine greater than 1.7 mg/dL or glomerular filtration rate less than 30 mL/min/1.73 m2
- Current serious or unstable medical illnesses including heart, liver, kidney, gastroenterologic, lung, endocrinologic, neurologic, psychiatric, immunologic, or blood disease and other conditions that could interfere with participant safety
- Life expectancy of less than 4 years
- History of recurrent kidney stones
- Unable to undergo magnetic resonance imaging (MRI), such as pacemaker, metallic implants, or severe claustrophobia
- History of chronic psychiatric illness (e.g., schizophrenia or bipolar disorder), major depression within last 2 years, current Global Depression Scale score greater than 6, or any recent suicide attempts or suicidal ideation
- History within the last 5 years of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis), or head trauma resulting in loss of consciousness for more than 10 minutes or any persistent cognitive deficit
- History of chronic alcohol or drug abuse/dependence within the past 5 years
- History within the last 5 years of a primary or recurrent malignant disease with the exceptions of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or non-metastatic prostate cancer with a normal prostate-specific antigen post-treatment
- Poor venous access such that multiple blood draws would be prevented
- Prohibited medications: regular use of benzodiazepines, antipsychotics, narcotics, cholinesterase inhibitors, memantine, or anti-epileptic drugs. Stable doses of SSRI or SNRI antidepressants will be allowed if dose does not change throughout the study.
- No additional supplements containing vitamin D will be allowed
Participants will be randomly assigned to take either a high-dose tablet of vitamin D3 (4,000 IU) or a standard-dose tablet (600 IU) daily for 3 years. Vitamin D levels will be measured every 6 months through blood draws. Researchers will measure changes in cognitive function and brain structure through cognitive tests and MRI scans.
University of California, Davis Alzheimer's Disease Center
University of California, Davis
- National Institutes of Health (NIH)
- National Institute on Aging (NIA)
|John Olichney, MD||Principal Investigator||UC Davis Alzheimer's Disease Center|
Phase II RCT of High-dose Vitamin D Supplements in Older Adults
- Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011 Jan;96(1):53-8. doi: 10.1210/jc.2010-2704. Epub 2010 Nov 29.
- Mungas D, Reed BR, Crane PK, Haan MN, Gonzlez H. Spanish and English Neuropsychological Assessment Scales (SENAS): further development and psychometric characteristics. Psychol Assess. 2004 Dec;16(4):347-59.
- Farias ST, Mungas D, Reed BR, Cahn-Weiner D, Jagust W, Baynes K, Decarli C. The measurement of everyday cognition (ECog): scale development and psychometric properties. Neuropsychology. 2008 Jul;22(4):531-44. doi: 10.1037/0894-4184.108.40.2061.
- Annweiler C, Allali G, Allain P, Bridenbaugh S, Schott AM, Kressig RW, Beauchet O. Vitamin D and cognitive performance in adults: a systematic review. Eur J Neurol. 2009 Oct;16(10):1083-9. doi: 10.1111/j.1468-1331.2009.02755.x. Epub 2009 Jul 29. Review.
- Annweiler C, Dursun E, Fron F, Gezen-Ak D, Kalueff AV, Littlejohns T, Llewellyn DJ, Millet P, Scott T, Tucker KL, Yilmazer S, Beauchet O. 'Vitamin D and cognition in older adults': updated international recommendations. J Intern Med. 2015 Jan;277(1):45-57. doi: 10.1111/joim.12279. Epub 2014 Jul 19. Review.
- Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, Fried L, Kestenbaum BR, Kuller LH, Langa KM, Lopez OL, Kos K, Soni M, Llewellyn DJ. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014 Sep 2;83(10):920-8. doi: 10.1212/WNL.0000000000000755. Epub 2014 Aug 6.
- Annweiler C, Fantino B, Schott AM, Krolak-Salmon P, Allali G, Beauchet O. Vitamin D insufficiency and mild cognitive impairment: cross-sectional association. Eur J Neurol. 2012 Jul;19(7):1023-9. doi: 10.1111/j.1468-1331.2012.03675.x. Epub 2012 Feb 16.
- Annweiler C, Karras SN, Anagnostis P, Beauchet O. Vitamin D supplements: a novel therapeutic approach for Alzheimer patients. Front Pharmacol. 2014 Jan 28;5:6. doi: 10.3389/fphar.2014.00006. eCollection 2014.
- Hooshmand B, Lkk J, Solomon A, Mangialasche F, Miralbell J, Spulber G, Annerbo S, Andreasen N, Winblad B, Cedazo-Minguez A, Wahlund LO, Kivipelto M. Vitamin D in relation to cognitive impairment, cerebrospinal fluid biomarkers, and brain volumes. J Gerontol A Biol Sci Med Sci. 2014 Sep;69(9):1132-8. doi: 10.1093/gerona/glu022. Epub 2014 Feb 25.
- MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985 Oct;76(4):1536-8.
- Buell JS, Dawson-Hughes B. Vitamin D and neurocognitive dysfunction: preventing "D"ecline? Mol Aspects Med. 2008 Dec;29(6):415-22. doi: 10.1016/j.mam.2008.05.001. Epub 2008 May 13. Review.
- Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, Ferrucci L, Melzer D. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med. 2010 Jul 12;170(13):1135-41. doi: 10.1001/archinternmed.2010.173.
- Miller JW, Harvey DJ, Beckett LA, Green R, Farias ST, Reed BR, Olichney JM, Mungas DM, DeCarli C. Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults. JAMA Neurol. 2015 Nov;72(11):1295-303. doi: 10.1001/jamaneurol.2015.2115.
- 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. Review.
- Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18. Review.
- Martins D, Meng YX, Tareen N, Artaza J, Lee JE, Farodolu C, Gibbons G, Norris K. The Effect of Short Term Vitamin D Supplementation on the Inflammatory and Oxidative Mediators of Arterial Stiffness. Health (Irvine Calif). 2014 Jun;6(12):1503-1511.