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High-dose Vitamin D Supplements in Older Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03613116
Recruitment Status : Recruiting
First Posted : August 2, 2018
Last Update Posted : May 15, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Information provided by (Responsible Party):
University of California, Davis

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.

Condition or disease Intervention/treatment Phase
Vitamin D Deficiency Cognitive Decline Dietary Supplement: Vitamin D3 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel Randomized Double-Blind Intervention of high-dose versus standard-dose vitamin D3.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Participants receive identically appearing capsules which contain either 4,000 IU (high-dose) or 600 IU (standard-dose) of vitamin D3.
Primary Purpose: Treatment
Official Title: Phase II RCT of High-dose Vitamin D Supplements in Older Adults
Actual Study Start Date : March 18, 2019
Estimated Primary Completion Date : March 30, 2022
Estimated Study Completion Date : March 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: High Dose Vitamin D3
Receives 4000 IU daily Vitamin D3 tablets.
Dietary Supplement: Vitamin D3
One-half of each diagnostic group will be randomized to treatment with high-dose vitamin D3 or to standard dose Vitamin D
Other Name: Cholecalciferol

Active Comparator: Standard Dose Vitamin D3
Receives 600 IU Vitamin D3 tablets.
Dietary Supplement: Vitamin D3
One-half of each diagnostic group will be randomized to treatment with high-dose vitamin D3 or to standard dose Vitamin D
Other Name: Cholecalciferol




Primary Outcome Measures :
  1. Correction of VitD insufficiency [ Time Frame: Expect vitamin D levels to correct by 1-2 month on treatment ]
    Correction of VitD insufficiency in all subjects treated with high dose VitD (defined as serum 25-hydroxyvitamin D ≥ 20.0 ng/ml)

  2. SENAS Executive Function Composite Score [ Time Frame: 3.5 years ]
    Change in SENAS executive function score from Baseline Visit to last Visit (month 42)


Secondary Outcome Measures :
  1. Evaluate effect of VitD on Cognitive Change [ Time Frame: 3.5 years ]
    Provide an estimate on effect sizes of treatment on cognitive change in ADAS-Cog global cognition score from baseline Visit to last Visit (month 42)



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years to 90 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inclusion criteria for this study are: 1) Age 65-90; 2) Low Vitamin D status, defined by a serum 25-OHD <20 ng/ml, as measured by competitive immunoassay at the Screening visit; 3) Fluent in either English or Spanish; 4) Willingness to be randomized to high-dose vs. standard dose vitamin D; 5) Education adjusted scores between 12-30 on the Montreal Cognitive Assessment (MOCA) at baseline; 6) A consensus clinical diagnosis of No Cognitive Impairment, Mild Cognitive Impairment, or mild AD dementia.
  • 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.

Exclusion Criteria:

  • Exclusion criteria (for all participants) are: 1) Lacks adequate vision, hearing, or literacy to complete the required psychometric tests (e.g. severe bilateral deafness despite use of hearing aids, or visual acuity poorer than 20/100 in both eyes); 2) Hepatic insufficiency, defined by either albumin <3.3 g/dL or by a value >2X the upper limit of normal (ULN) in either alanine aminotransaminase (ALT/SGPT) or bilirubin, or >3X the ULN for aspartate aminotransaminase (AST/SGOT); 3) Renal insufficiency, defined by either serum creatinine >1.7 mg/dL or glomerular filtration rate <40 mL/min/1.73 m2; (calculated per CKD-EPI formula). 4) Hypercalcemia, defined by serum calcium level >2 standard deviations above the mean. Corrected Calcium mg/dL = [0.8*(4.0g/dL - Patients Albumin g/dL)] + Serum Calcium mg/dL (X of 8.6-10.5 is in normal range; formula accurate only if Albumin is in 3.2-4.6 range). 5) Current serious or unstable medical illnesses including cardiovascular (e.g. unstable ischemic cardiovascular disease), hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the participant being able to safely take high-dose vitamin D for the 3.5 year study duration; or has a life expectancy of <4 years; 6) History of recurrent renal stones; 7) Unable to undergo MRI scanning (e.g. pacemaker, metallic implants, severe claustrophobia); 8) Subjects with a history of osteoporosis will be excluded if the Screening serum 25-OHD level is < 12 ng/ml. 9) History of chronic psychiatric illness (e.g. schizophrenia, bipolar disorder), any episode of major depression within last 2 years, or current GDS > 6, any recent suicide attempts or suicidal ideation; 10) history within the last 5 years of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis), or head trauma resulting in protracted loss of consciousness (>10 minutes) or any persistent cognitive deficit; 11) History of chronic alcohol or drug abuse/dependence as defined by DSM-IV, within the past 5 years; 12) 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; 13) Does not have good venous access, such that multiple blood draws would be precluded; 14) Regular use of any of these CNS active medications: benzodiazepines, antipsychotics, narcotics, cholinesterase inhibitors, memantine or anti-epileptic drugs. Stable doses of SSRIs or SNRI anti-depressants will be allowed, and included persons will be discouraged to change the doses of any potentially CNS active medication throughout the 3.5-year study. 15) Those who plan to change their dosage of any vitamin supplement during the duration of the study may be discontinued from the clinical trial. Changes in vitamin supplement dosing (e.g. vitamin B12) will only be allowed if a specific deficiency has been found. If participants are taking vitamin D supplementation (e.g. in a daily multi-vitamin) at the time of screening, they should continue on this same dose of vitamin supplementation throughout the duration of the randomized clinical trial. 16) Current participation in any clinical trial involving experimental AD therapies (anti-amyloid, anti-tau, etc.). 17) Female subjects who are pregnant or plan to become pregnant during participation in this trial. 18) Inability to swallow oral capsules.
  • We will not exclude subjects with stable coronary artery disease or vascular risk factors such as diabetes or hypertension, who otherwise meet our inclusion/exclusion criteria. We will allow inclusion of participants with prior TIA or prior history of one stroke, but will exclude those with past history of multiple strokes. We will allow participants with up to two incidental infarcts on structural MRI, because the presence of cerebrovascular disease is very common in any representative sample of U.S. elderly persons, and may be an important contributor to dementia and age-associated cognitive decline. We will not exclude those with severe white matter (WM) hyperintensities, for similar reasons.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03613116


Contacts
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Contact: Maria Levallois 9167345245 melevallois@ucdavis.edu
Contact: Hongzheng Zhang 9253576914 hzzhang@ucdavis.edu

Locations
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United States, California
University of California, Davis Alzheimer's Disease Center Recruiting
Walnut Creek, California, United States, 94598
Contact: Maria Levallois    916-734-5245    melevallois@ucdavis.edu   
Contact: Hongzheng Zhang    9253576914    hzzhang@ucdavis.edu   
Sponsors and Collaborators
University of California, Davis
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Investigators
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Principal Investigator: John Olichney, MD UC Davis Alzheimer's Disease Center

Publications:

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Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT03613116    
Other Study ID Numbers: 1129309
R01AG051618 ( U.S. NIH Grant/Contract )
First Posted: August 2, 2018    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: It is not yet known if there will be a plan to make IPD available

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of California, Davis:
vitamin D
cognitive decline
Additional relevant MeSH terms:
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Vitamin D Deficiency
Cognitive Dysfunction
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents