Vitamin D as a Therapeutic Adjunct in the Stimulant Treatment of ADHD: a Proof-of-concept Tele-health Study of Stimulant-induced Improvement in Neurocognitive Functioning.

The purpose of this study is to assess vitamin D as a therapeutic adjunct in the stimulant treatment of ADHD.

Study Overview

• Status: Terminated
• Conditions: ADHD
• Intervention / Treatment: Drug: Calcitriol; Other: Placebo

Detailed Description

The specific aim of this study is to determine whether acute calcitriol (vitaminD) administration (compared to placebo) enhances the neurocognitive effects of of current stimulant medications as measured by tasks of vigilance/attention, spatial working memory, and reversal learning in individuals with (attention deficit hyperactivity disorder (ADHD) using a randomized, double-blind, placebo controlled, within-subject, two-day study design.

Primary Hypothesis: It is hypothesized that calcitriol (versus placebo) administration will enhance positive neurocognitive effects of current stimulant medications in individuals with ADHD.

Secondary (Exploratory) Hypothesis: It is hypothesized that calcitriol (versus placebo) administration alone will also enhance neurocognitive performance on tasks of attention/vigilance and/or spatial working memory.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • CMHC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18-50 years
• Voluntary, written, informed consent
• Physically healthy by medical and psychiatric history
• DSM-5 diagnosis of ADHD
• Point of Care Test results for Vitamin D equal or higher than 20 ng/ml
• English speaking

Exclusion Criteria:

• 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), except ADHD
• A history of significant medical (e.g., cardiovascular, diabetic/metabolic) or neurological (e.g., cerebrovascular accidents, seizure, traumatic brain injury) illness
• Current use of psychotropic and/or potentially psychoactive prescription medications, except prescribed stimulants
• Use of any prescription medications and/or over-the-counter medications, vitamins (including vitamin D) and/or herbal supplements which could have a negative clinical interaction with calcitriol 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,).
• Levels of 25(OH)D3 below 20 ng/ml .
• History of kidney stones within the past 5 years
• History 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 calcitriol
• Malabsorption syndromes (i.e. Celiac sprue)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; A total of 24 otherwise medically healthy individuals with ADHD will be studied as outpatients. All subjects will undergo neurocognitive assessments of attention/vigilance, spatial working memory, and reversal learning both before and after subjects' daily dosing with their currently prescribed stimulant medication on both calcitriol and placebo pretreatment days using a randomized, double-blind, placebo controlled, within-subject, two-day study design.
Experimental: Calcitriol	Drug: Calcitriol; A total of 24 otherwise medically healthy individuals with ADHD will be studied as outpatients. All subjects will undergo neurocognitive assessments of attention/vigilance, spatial working memory, and reversal learning both before and after subjects' daily dosing with their currently prescribed stimulant medication on both calcitriol and placebo pretreatment days using a randomized, double-blind, placebo controlled, within-subject, two-day study design.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enhanced positive neurocognitive effects on the CPT-IP	On the Continuous Performance Task (CPT-IP) subjects are shown a random sequence of different numbers and are instructed to press a button as quickly and accurately as possible upon detection of two identical pairs of numbers, and to withhold their response to any other sequence of letters. Outcomes will be measured by d prime.	Up to 5 hours
Enhanced positive neurocognitive effects on the Spatial working memory task	The spatial working memory task is a measure of working memory. As part of the task, stimuli will be projected onto the computer screen and target stimuli can be spatial locations, different visual stimuli, sound or text. Outcomes will be measured by percent correct.	Up to 5 hours
Enhanced positive neurocognitive effects on the PRLT	The Probabilistic Reversal Learning Task (PRLT) measures subjects' perseverative responding in the context of changing reward contingencies / cues. Outcomes will be measured by numbers of reversal achieved, total points, and error types.	Up to 5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enhanced positive neurocognitive effects on the CPT-IP- hits	Enhanced positive neurocognitive effects on the CPT-IP will be measured by counts of hits, false alarms, and random errors.	Up to 5 hours
Enhanced positive neurocognitive effects on the CPT-IP- false alarms	Enhanced positive neurocognitive effects on the CPT-IP will be measured by counts of hits, false alarms, and random errors.	Up to 5 hours
Enhanced positive neurocognitive effects on the CPT-IP- random errors	Enhanced positive neurocognitive effects on the CPT-IP will be measured by counts of hits, false alarms, and random errors.Enhanced positive neurocognitive effects on the CPT-IP will be measured by counts of hits, false alarms, and random errors.Enhanced positive neurocognitive effects on the CPT-IP will be measured by counts of hits, false alarms, and random errors.	Up to 5 hours
Spatial working memory task- reaction time	Enhanced positive neurocognitive effects be measured by reaction time on the spatial working memory task.	Up to 5 hours
Enhanced positive neurocognitive effects on the PRLT - win-switch / lose-stay rate	Enhanced positive neurocognitive effects on the PRLT will be measured by win-switch / lose-stay rate.	Up to 5 hours

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Marc Potenza, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2020
• Primary Completion (Actual): September 29, 2020
• Study Completion (Actual): September 29, 2020

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 13, 2020

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Calcitriol
• Other Study ID Numbers: 2000028035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No