NCT03103750

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

Vitamin D as a Therapeutic Adjunct in the Stimulant Treatment of ADHD: a Proof-of-concept Study of Stimulant-induced Dopamine Release Using [11C]-PHNO PET in Healthy Humans

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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-IP), after treatment with amphetamine. Hypothesis: Investigators hypothesize that Subjects pre-treated with calcitriol will have faster reaction times/higher accuracy on the CPT-IP 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.

Conditions

• ADHD

Interventions

Type	Name	Description
PROCEDURE	Magnetic Resonance Imaging (MRI)	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
DRUG	PHNO	Used as a tracer for in vivo imaging.
DIETARY_SUPPLEMENT	calcitriol	three 0.5 mcg capsules
DRUG	Placebo oral capsule	three 0.5 mcg capsules
PROCEDURE	high-resolution research tomography	A functional imaging technique that is used to observe metabolic processes in the body.
DRUG	Dextro Amphetamine	Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg

Timeline

• Start date: 2017-08-15
• Primary completion: 2023-01-17
• Completion: 2023-01-17
• First posted: 2017-04-06
• Last updated: 2024-03-19
• Results posted: 2024-03-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study