High-dose Vitamin D Supplements in Older Adults

NCT03613116 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: 1129309R01AG051618
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase II randomized clinical trial aims to test if supplementation with high dose oral vitamin D will successfully correct vitamin D insufficiency, compared to treatment with standard (RDA) dose vitamin D in a diverse community-based elderly cohort. The effect of high-dose vs. standard-dose vitamin D on altering cognitive trajectories will also be assessed and data will be expected to be used in designing a potential definitive Phase III trial in elderly groups at risk for dementia. A total of 180 elderly persons with longitudinal biomarkers, neuropsychological testing and brain MRI scans will be enrolled, with 152 (\~50 with MCI, 50 with mild AD and 50 with no cognitive impairment) expected to complete the 3½-year study. One-half of each diagnostic group will be randomized to treatment with high-dose vitamin D3 (4,000 IU daily) or to standard dose Vitamin D (600 IU capsule daily + \~200 IU dietary = \~800 IU total/day). Longitudinal MRI analyses will provide an estimate of the treatment effect size on brain atrophy rate. Vitamin D receptor genotype polymorphisms and their impact on response to oral supplementation will also be examined. If vitamin D supplementation improves cognitive outcome, this could have a large impact on the public health, since low vitamin D status is a common, readably treatable condition which may provide a novel window to prevent dementia and AD. Furthermore, the higher prevalence of AD and dementia in African Americans and Latinos could be partially attributable to vitamin D insufficiency.

Conditions

Vitamin D Deficiency; Cognitive Decline

Keywords

vitamin D; cognitive decline

Outcome Measures

Primary Outcomes (2)

• Correction of VitD insufficiency

  Correction of VitD insufficiency in all subjects treated with high dose VitD (defined as serum 25-hydroxyvitamin D ≥ 20.0 ng/ml)

  Expect vitamin D levels to correct by 1-2 month on treatment

• SENAS Executive Function Composite Score

  Change in SENAS executive function score from Baseline Visit to last Visit (month 42)

  3.5 years

Secondary Outcomes (1)

• Evaluate effect of VitD on Cognitive Change

  3.5 years

Study Arms (2)

High Dose Vitamin D3

EXPERIMENTAL

Receives 4000 IU daily Vitamin D3 tablets.

Dietary Supplement: Vitamin D3

Standard Dose Vitamin D3

ACTIVE COMPARATOR

Receives 600 IU Vitamin D3 tablets.

Dietary Supplement: Vitamin D3

Interventions

Vitamin D3 DIETARY_SUPPLEMENT

One-half of each diagnostic group will be randomized to treatment with high-dose vitamin D3 or to standard dose Vitamin D

Also known as: Cholecalciferol

High Dose Vitamin D3; Standard Dose Vitamin D3

Eligibility Criteria

• Age: 65 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• In order to be included in the No Cognitive Impairment (NC) subgroup, an individual must show no significant cognitive impairment on the baseline neuropsychological tests. Diagnoses are made by a comprehensive case conference review, including investigators from both sites, resulting in a consensus diagnosis made according to current research criteria. We will also require a minimum MOCA score of 23 or above for those with education \>12 y, or MOCA \>20 (uncorrected score) for those with education \<12 years. These subjects are expected to mostly have CDR global scores of 0, but we will not exclude CDR=0.5, as long as Peterson criteria (Petersen, Journal of Internal Medicine 2004) for MCI (amnestic or non-amnestic) are not met and the CDR-Sum of Boxes is \<1.0. Similarly, we will not exclude elderly with subjective memory complaints from the NC group.
• In order to be included in the Mild Cognitive Impairment (MCI) subgroup, a participant will need to meet research criteria for amnestic MCI, either single-domain or multiple-domain (McKhann et al, Neurology 1984). Thus, participants with amnestic MCI will have standardized memory scores \>1.5 SDs below average, and if cognitive scores in other cognitive domains are also \>1.5 SDs below average they will be classified as multiple-domain amnestic MCI. All MCI participants will be required to have a global CDR=0.5. In addition, we will require a minimum MOCA score of \>20 for those with education \>12 y, or MOCA \>17 (uncorrected score) for those with education \<12 years.
• In order to be included in the Mild AD dementia subgroup, a participant will need to meet research criteria for probable or possible AD (McKhann et al, Neurology 1984). A global CDR score of 1 will be required (mild dementia). In addition, we will require a minimum MOCA score of \>15 at entry for those with education \>12 y, or MOCA \>12 (uncorrected score) for those with education \<12 y. AD therapies will be allowed (e.g. donepezil, memantine) as long as doses have been stable for \>6 weeks, and no changes in doses or CNS active medications are planned while participating in this trial.

Sponsors & Collaborators

• University of California, Davis: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of California, Davis Alzheimer's Disease Center

Walnut Creek, California, 94598, United States

Location

Related Publications (16)

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MeSH Terms

Conditions

Vitamin D Deficiency; Cognitive Dysfunction

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• John Olichney, MD

  UC Davis Alzheimer's Disease Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants receive identically appearing capsules which contain either 4,000 IU (high-dose) or 600 IU (standard-dose) of vitamin D3.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel Randomized Double-Blind Intervention of high-dose versus standard-dose vitamin D3.

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: August 2, 2018
• Study Start: March 18, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 30, 2025

Record last verified: 2025-03

Locations

US (1)