New Haven, Connecticut 06519

  • ADHD

Purpose:

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.


Study summary:

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.


Criteria:

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


Study is Available At:


Original ID:

1612018712


NCT ID:

NCT03103750


Secondary ID:

M# 25288


Study Acronym:


Brief Title:

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


Official Title:

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


Overall Status:

Recruiting


Study Phase:

Phase 1/Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

50 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Yale University


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

24


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Marc Potenza, PhD, MD
Principal Investigator
Yale University
Primary Contact:Jessica Costeines, MSW
203-974-7559
Jessica.costeines@yale.edu

Study Dates

Start Date:August 15, 2017
Completion Date:January 2022
Completion Type:Anticipated
Primary Completion Date:January 2022
Primary Completion Type:Anticipated
Verification Date:February 2021
Last Changed Date:February 24, 2021
First Received Date:March 30, 2017

Study Outcomes

Outcome Type:Secondary Outcome
Measure:continuous Performance Task (CPT-AX)
Time Frame:day 7
Safety Issues:False
Description:In this computer based test the subjects are shown a random sequence of different letters and are instructed to press a button as quickly and accurately as possible (with their preferred hand) upon detection of an X after an A, and to withhold their respo
Outcome Type:Secondary Outcome
Measure:continuous Performance Task (CPT-AX)
Time Frame:day 1
Safety Issues:False
Description:In this computer based test the subjects are shown a random sequence of different letters and are instructed to press a button as quickly and accurately as possible (with their preferred hand) upon detection of an X after an A, and to withhold their respo
Outcome Type:Primary Outcome
Measure:non-displaceable tracer binding potentials
Time Frame:day 7
Safety Issues:False
Description:non-displaceable tracer binding potentials (BPND = VT - VREF / VREF), which are linearly proportional to the density of available D2/3 Rs, computed using a simplified reference tissue model (SRTM) utilizing the cerebellum as a reference region.
Outcome Type:Primary Outcome
Measure:non-displaceable tracer binding potentials
Time Frame:day 1
Safety Issues:False
Description:non-displaceable tracer binding potentials (BPND = VT - VREF / VREF), which are linearly proportional to the density of available D2/3 Rs, computed using a simplified reference tissue model (SRTM) utilizing the cerebellum as a reference region.

Study Interventions

Intervention Type:Drug
Name:Dextro Amphetamine
Description:Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg
Arm Name:Calcitriol then placebo
Other Name:Dexedrine
Intervention Type:Procedure
Name:high-resolution research tomography
Description:A functional imaging technique that is used to observe metabolic processes in the body.
Arm Name:Calcitriol then placebo
Other Name:PET scan
Intervention Type:Drug
Name:Placebo oral capsule
Description:three 0.5 mcg capsules
Arm Name:Calcitriol then placebo
Intervention Type:Dietary Supplement
Name:calcitriol
Description:three 0.5 mcg capsules
Arm Name:Calcitriol then placebo
Intervention Type:Drug
Name:PHNO
Description:Used as a tracer for in vivo imaging.
Arm Name:Calcitriol then placebo
Intervention Type:Procedure
Name:Magnetic Resonance Imaging (MRI)
Description: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
Arm Name:Calcitriol then placebo

Study Arms

Study Arm Type:Experimental
Arm Name:Placebo then Calcitriol
Description:Healthy volunteers will receive a baseline MRI. On the night before, and day of testing subjects will receive two doses of calcitriol or placebo, followed by PHNO injection & PET Scan #1. A minimum of six days later, subjects will receive a Dexedrine Dose followed by a second PHNO injection and PET scan #2.
Study Arm Type:Experimental
Arm Name:Calcitriol then placebo
Description:Healthy volunteers will receive a baseline MRI. On the night before, and day of testing subjects will receive two doses of calcitriol or placebo, followed by PHNO injection & PET Scan #1. A minimum of six days later, subjects will receive a Dexedrine Dose followed by a second PHNO injection and PET scan #2.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Yale University
Agency Class:Other
Agency Type:Collaborator
Agency Name:Brain & Behavior Research Foundation

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: September 16, 2021

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