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

NCT03103750 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 2000020604M# 252881R01AT010508-01A1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

ADHD

Keywords

Vitamin D

Outcome Measures

Primary Outcomes (2)

• Non-displaceable Tracer Binding Potentials

  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.

  day 1

• Non-displaceable Tracer Binding Potentials

  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.

  day 7

Secondary Outcomes (2)

• Continuous Performance Task (CPT-IP)

  day 1

• Continuous Performance Task (CPT-IP)

  day 7

Study Arms (2)

Calcitriol then placebo

EXPERIMENTAL

Healthy volunteers will receive a baseline MRI. On the night before and day of testing, subjects will receive two doses of calcitriol (3.0mcg total), followed by PHNO injection and PET Scan #1. After PET Scan #1, subjects will receive a Dexedrine dose, followed by PHNO injection and PET Scan #2. A minimum of six days later, subjects will receive two doses of placebo for the night before and day of testing, followed by a third PHNO injection and PET scan #3. After PET scan #3, subjects will receive another Dexedrine dose, followed by PHNO injection and PET scan #4.

Procedure: Magnetic Resonance Imaging (MRI); Drug: PHNO; Dietary Supplement: calcitriol; Drug: Placebo oral capsule; Procedure: high-resolution research tomography; Drug: Dextro Amphetamine

Placebo then Calcitriol

EXPERIMENTAL

Healthy volunteers will receive a baseline MRI. On the night before and day of testing, subjects will receive two doses of placebo, followed by PHNO injection and PET Scan #1. After PET Scan #1, subjects will receive a Dexedrine dose, followed by PHNO injection and PET Scan #2. A minimum of six days later, subjects will receive two doses of calcitriol (3.0mcg total) for the night before and day of testing, followed by a third PHNO injection and PET scan #3. After PET scan #3, subjects will receive another Dexedrine dose, followed by PHNO injection and PET scan #4.

Procedure: Magnetic Resonance Imaging (MRI); Drug: PHNO; Dietary Supplement: calcitriol; Drug: Placebo oral capsule; Procedure: high-resolution research tomography; Drug: Dextro Amphetamine

Interventions

Magnetic Resonance Imaging (MRI) PROCEDURE

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

Calcitriol then placebo; Placebo then Calcitriol

PHNO DRUG

Used as a tracer for in vivo imaging.

Calcitriol then placebo; Placebo then Calcitriol

calcitriol DIETARY_SUPPLEMENT

three 0.5 mcg capsules

Calcitriol then placebo; Placebo then Calcitriol

Placebo oral capsule DRUG

three 0.5 mcg capsules

Calcitriol then placebo; Placebo then Calcitriol

high-resolution research tomography PROCEDURE

A functional imaging technique that is used to observe metabolic processes in the body.

Also known as: PET scan

Calcitriol then placebo; Placebo then Calcitriol

Dextro Amphetamine DRUG

Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg

Also known as: Dexedrine

Calcitriol then placebo; Placebo then Calcitriol

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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-5 psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, etc.) as determined by the Structured Clinical Interview for DSM-5 (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.

Sponsors & Collaborators

• Yale University: lead
• Brain & Behavior Research Foundation: collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Magnetic Resonance Spectroscopy; Calcitriol; Dextroamphetamine

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Marc Potenza, PhD, MD
• Organization: Yale School of Medicine

marc.potenza@yale.edu

(203) 974-7356

Study Officials

• Marc Potenza, PhD, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a within-subject, two-day four-scan, randomized, double-blind, placebo-controlled study design.

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: April 6, 2017
• Study Start: August 15, 2017
• Primary Completion: January 17, 2023
• Study Completion: January 17, 2023
• Last Updated: March 19, 2024
• Results First Posted: March 19, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)