The Efficacy of Vitamin D Supplementation to Sustain Performance Outcomes

Assessment of the Efficacy of Vitamin D Supplementation to Sustain Performance of Military-Relevant Laboratory Tasks Under Acutely Stressed Conditions: A Randomized, Double-Blind, Placebo-Controlled Study

The goal of this clinical trial is to find out if vitamin D supplements help healthy adults maintain their cognitive and simple physical task performance and emotional state during highly stressful situations.

The main question it aims to answer is:

- Does vitamin D help maintain cognitive and physical task performance and emotional state during highly stressful situations?

Researchers will compare vitamin D to placebo (a look-alike tablet that contains no active ingredients) to see if vitamin D better maintain cognitive and physical task performance and emotional state during highly stressful situations.

Participants will:

• Take vitamin D or placebo tablets daily for 8 weeks.
• Perform cognitive and simple physical tasks and rate their emotional state under highly stressful situations.
• Wear a stress belt that delivers mild electric shocks 1 - 5 times while participants are performing laboratory tasks.
• Wear a wristwatch-shaped activity monitor for 9 weeks.
• Visit the laboratory 5 times.

Inclusion Criteria:

• Male and non-pregnant, non-lactating females 18 to 40 (inclusive) years of age.
• Females of child-bearing potential must be using some form of birth control, if sexually active (e.g., oral contraceptive, condom, intrauterine device, etc.)
• Score of 80% or greater on a "Volunteer Comprehension Assessment" test. A maximum of two attempts is permitted.
• Blood 25 hydroxy vitamin D [25(OH)D] levels at the Screening visit of 30 nmol/L (12 ng/mL) (inclusive) - < 75 nmol/L (30 ng/mL).

Exclusion Criteria:

• Contraindications due to vitamin D supplementation, including a history of hypercalcemia, malabsorption syndrome, hypervitaminosis D, or allergic/hypersensitivity reactions to vitamin D or a history of other adverse reactions to vitamin D supplementation.
• Taking a vitamin D3 or D2 supplement or a supplement containing vitamin D3 or D2 (excluding vitamin D-fortified foods) during the participation. Volunteers who take vitamin D3 or D2 supplement before their participation can be eligible if they agree to stop taking the supplement(s) starting 1 month prior to the enrollment/baseline visit until the end of the post-supplementation visit. Blood 25(OH)D levels of the volunteers who stopped taking the supplements after the screening visit will be tested before the Enrollment/Baseline visit to ensure their 25(OH)D fall within the inclusionary ranges. Volunteers who are not able to stop taking vitamin D supplements or supplements containing vitamin D due to medical/health or any other reasons (especially if the volunteer is taking supplements containing vitamin D under the direction of a healthcare provider) are not eligible.
• Not being able to tolerate electric shocks delivered through the stress belt.
• Self-reported propensity for adverse skin reactions, such as excessive irritation, burning, itching, hives, and redness, in response to physical or heat stimuli.
• A history of abuse or addiction to recreational or illicit drugs (including marijuana and alcohol) or prescribed medications (e.g., opioids) (diagnosed or suspected based on the medical history).
• Use a nicotine product (e.g., cigarette, cigar, vape) more than 3 days per week or not be able to go without using these products during any lab visits.
• Self-reported caffeine use in excess of 600 mg (e.g., approximately 10 caffeinated sodas or approximately 29 ounces of brewed coffee) per day on average or not being able to go without caffeine during the in-lab visits.
• History of neurologic disorder (to include but not limited to epilepsy, hydrocephalus, multiple sclerosis). An infrequent or resolved single neurological event (e.g., childhood seizure, rare sporadic migraine headaches, resolved meningeal infection with no sequelae) or a history of mild traumatic brain injury may be deemed non-exclusionary at the discretion of the examining study medical investigator.
• Score of 10 or above on the Beck Depression Inventory (BDI) or a score of > 0 on item 9 "Suicidal Thoughts or Wishes" of the BDI.
• Score of 33 or above on the Posttraumatic Stress Disorder (PTSD) Checklist, 5th Edition.
• Score 20 or above on the Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Anxiety-7-Item Short form.
• History of cardiovascular disease (to include but not limited to arrhythmias, valvular heart disease, congestive heart failure, history of sudden cardiac death or myocardial infarction).
• Asthma, any type of reactive airways disease, or any pulmonary disease requiring daily inhaler use.
• Regularly work night shifts or have a habitual sleep/wake schedule that is not conducive for the optimal performance on cognitive, physical, and/or emotional tasks during the study visits (e.g., extremely early or late habitual bedtime or rise time; to be determined on a case-by-case basis by the principal investigator or an associate investigator).
• A diagnosis of sleep apnea.
• Kidney disease or kidney abnormalities, liver disease or liver abnormalities, or any other metabolic derangements (endocrine disorders, hyperglycemia, etc.) that could alter neurophysiological function.
• History of kidney stones.
• Osteoporosis or low bone density.
• Self-reported history of hospitalization for a psychiatric disorder within the past year or with a previous history of a psychotic, bipolar disorder or personality disorder. For a history of a diagnosis of any other psychiatric disorder, the potential participant's symptoms must either be resolved to a degree that a diagnosis is no longer applied or their symptoms must have been stabilized by pharmacological or nonpharmacological treatments for a period of at least 90 days or greater as deemed exclusionary or non-exclusionary at the discretion of the examining study medical investigator.
• Self-reported or suspected current use of antipsychotics, anticonvulsants, or mood stabilizers, to be determined on a case-by-case basis by the examining study medical investigator.
• Self-reported or suspected current use of products or drugs that have central nervous system depressant effects, to be determined on a case-by-case basis by the examining study medical investigator.
• Self-reported or suspected use of products or drugs that are contraindicated to the study supplement or significantly affect the participant's study performance and that cannot be safely discontinued during the study participation. To be determined on a case-by-case basis by the examining study medical investigator.
• Self-reported or suspected current heavy alcohol use (minimum limit to define heavy alcohol use is 14 drinks per week for males and 7 drinks per week for females or as determined by the examining study medical investigator).
• (Females only) Positive urine pregnancy test result.
• (Females only) Self-reported or suspected current breast-feeding or collecting breast-milk.
• Resting blood pressure above 140/90 or resting pulse > 110 beats per minute.
• Body Mass Index (BMI) ≥ 31. The inclusion of individuals with BMI between 30 and 31 (Obese Class I) will be determined using medical investigator's discretion.
• Clinically significant values (as determined by the reviewing study medical investigator) for any hematology or chemistry parameter.
• Positive urine drug result at any study visits. If tetrahydrocannabinol is positive at the screening visit and the volunteer wishes to have the second drug test, the volunteer will be allowed to have one additional urine drug test after a 1 to 5-month waiting period.
• Positive saliva alcohol result at any study visits.
• Inability to read (i.e., failing in the Volunteer Comprehension Assessment twice) and sign consent.
• Failure to obtain required approved official leave to participate (federal civilian employees and active-duty military only).
• Failure to cooperate with requirements of the study.
• Self-reported or suspected current use of illicit drugs (including but not limited to benzodiazepines, amphetamines, and cocaine). In case of marijuana/tetrahydrocannabinol product use, the frequency up to twice a month will not be excluded. Current use of any other drugs at any frequency is excluded.
• Current use and/or prescription for any medication the medical investigator determines would interact adversely with vitamin D supplementation, including but not limited to: orlistat, statins, corticosteroid medications, and thiazide diuretics.
• Current diabetes.
• Gastrointestinal disorders - motility disorders that might affect vitamin D absorption.
• Failure to provide a social security number or tax identification number in order to be paid for screening and participation in the study.
• Current participation in another ongoing clinical trial.
• Prior participation in this study.