Vitamin D as a Therapeutic Adjunct in the Stimulant Treatment of ADHD

  • STATUS
    Recruiting
  • End date
    Aug 2, 2023
  • participants needed
    24
  • sponsor
    Yale University
Updated on 2 May 2022
dopamine
amphetamine
cns stimulants
dextroamphetamine
Accepts healthy volunteers

Summary

Specific Aim 1: As part of a within-subject, two-days, study design, to determine whether acute calcitriol (vs. placebo) pre-treatment is associated with greater amphetamine (Amp)-induced dopamine (DA) release in the caudate, putamen, ventral striatum (VST), and substantia nigra / ventral tegmental area (SN/VTA) of healthy human subjects.

Specific Aim 2: To determine whether acute calcitriol (vs. placebo) pre-treatment is associated with better performance on a test of attention (e.g., the continuous Performance Task or CPT-AX), after treatment with amphetamine. Hypothesis: Investigators hypothesize that Subjects pre-treated with calcitriol will have faster reaction times/higher accuracy on the CPT-AX vs. subjects pre-treated with placebo, after treatment with amphetamine.

Description

Increases in the rates of childhood ADHD over the past two decades have lead to speculation that calcitriol deficiency (e.g., secondary to the increased use of sunscreen and/or increases in sedentary, indoor lifestyles in children) plays a causal/contributory role in the etiology of ADHD. To date, evidence of a direct link is lacking. One study showed higher maternal circulating Vitamin D levels in pregnancy are associated with lower risk of developing ADHD-like symptoms in childhood. On the other hand, another study did not replicate the above association, and a prospective study using umbilical cord samples stored at the time of birth reported no difference in serum vitamin D levels between ADHD group versus healthy controls. In terms of clinical trials, one randomized double blind study among adults with ADHD reported a beneficial effect of the intervention, measured with the Conners Adult ADHR rating scale, in comparison with placebo, but the intervention included the combination of vitamin D and several other micronutrients. An analysis of moderators of a positive response to ADHD behaviors did not reveal a significant predictive effect of vitamin D.

However, recent studies provide intriguing indirect evidence of an inverse relationship between solar intensity (SI) and/or altitude (a proxy for greater sun/UV light exposure) and regional rates of ADHD. One study examined three large datasets across 49 U.S. states for 2003 and 2007, and across 9 non-U.S. countries. This study examined the prevalence of ADHD and Solar Intensity (SI) maps. They found an inverse association between solar intensity and prevalence of ADHD. Another study examined two national survey datasets. They found an inverse relationship between altitude and prevalence of ADHD. Investigators hypothesize, as suggested by Huber, that a common denominator on the above studies is the increased vitamin D levels in those exposed to a higher solar intensity, which is known to increase with altitude.

Details
Condition ADHD
Treatment Magnetic Resonance Imaging (MRI), Calcitriol, Placebo oral capsule, Raclopride, Raclopride, high-resolution research tomography, Dextro Amphetamine, Dextro Amphetamine, PHNO
Clinical Study IdentifierNCT03103750
SponsorYale University
Last Modified on2 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age 18-50 years
Voluntary, written, informed consent
Physically healthy by medical history, physical, neurological, ECG, and laboratory examinations
For females, non-lactating, with a negative serum or urine pregnancy test
Lab results without clinically relevant findings (e.g. renal function, electrolytes, and vitamin D levels)
English speaking

Exclusion Criteria

Medical contraindication to Dexedrine administration (e.g., history of cardiac problems, seizures, glaucoma, hypertension, hyperthyroidism, etc.)
Medical contraindication to calcitriol administration (e.g., history of hypersensitivity to calcitriol or any component of the formulation, hypercalcemia or vitamin D toxicity)
History of substance dependence (e.g., alcohol, opiates, sedative hypnotics), except for nicotine
A primary major DSM-V psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, etc.) as determined by the Structured Clinical Interview for DSM-V (SCID)
A history of significant medical (e.g., cardiovascular, diabetic/metabolic) or neurological (e.g., cerebrovascular accidents, seizure, traumatic brain injury) illness
Positive answers on the cardiac history questionnaire that may place the subject at higher risk, as determined by an internal medicine specialist or cardiologist's review of both the questionnaire responses and screening ECG
Current use of psychotropic and/or potentially psychoactive prescription medications
For females, laboratory (β-HCG) or physical evidence of pregnancy/lactation 9) MRI-incompatible implants and other contraindications for MRI (i.e., aneurysm clip, metal fragments, internal electrical devices such as a cochlear implant, spinal cord stimulator or pacemaker)
History of claustrophobia or feeling of inability to lie still on his/her back for the PET or MRI scans
History of any bleeding disorder or current anticoagulant therapy
Donation or loss of 550 mL of blood or more (including plasmapheresis) or receipt of a transfusion of any blood product within 8 weeks prior to the first test day
Use of any prescription medications and/or over-the-counter medications, vitamins and/or herbal supplements which could have a negative clinical interaction with calcitriol/Dexedrine or which could confound scientific results of the study, within 2 weeks prior to each test day (e.g., thiazide diuretics, Mg based antiacids, digoxin, etc,.)
Serum levels of 25(OH)D3 below 20 ng/ml
Obesity i.e. BMI over 30 (more prone to lower vitamin D levels)
Subjects with history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over Radioactive Drug Research Committee (RDRC) limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year
Subjects with current, past or anticipated exposure to radiation in the work place
History of kidney stones within the past 5 years
Any degree of renal failure
History of parathyroid disorder (hyper or hypoparathyroidism)
History of osteoporosis or any pathologic fractures
Vitamin D supplementation in any form in the past 3 months
Known hypersensitivity to Dexedrine, [11C]PHNO, or calcitriol
Malabsorption syndromes (i.e. Celiac sprue)
Serum corrected calcium > 10.5 mg/dl or phosphate > 4.2 mg/dl
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