Vitamin D as a Therapeutic Adjunct in the Stimulant Treatment of ADHD
Condition: ADHD
Study type: Interventional
Phase: Phase 1

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.
    

Detailed 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.
    

Intervention name(s): Magnetic Resonance Imaging (MRI); PHNO; calcitriol; Placebo oral capsule; high-resolution research tomography; Dextro Amphetamine
Intervention type(s): Procedure; Drug; Dietary Supplement; Drug; Procedure; Drug
Intervention description(s): Magnetic resonance imaging (MRI) scans (3 T) will be collected in each subject for the purposes of excluding participants with anatomical abnormalities and anatomically co-registering PET and MRI for image analysis; Used as a tracer for in vivo imaging.; three 0.5 mcg capsules; three 0.5 mcg capsules; A functional imaging technique that is used to observe metabolic processes in the body.; Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg
Other intervention name(s): PET scan; Dexedrine
Intervention MeSH terms: Calcitriol; Amphetamine; Dextroamphetamine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a within-subject, two-day four-scan, randomized, double-blind, placebo-controlled study design.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Vitamin D