Trial Outcomes & Findings for Vitamin D as a Therapeutic Adjunct in the Stimulant Treatment of ADHD (NCT NCT03103750)

Last Updated: 2024-03-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

day 1

Results posted on

2024-03-19

Participant Flow

Participant milestones

Participant milestones
Measure	Calcitriol Then Placebo 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg	Placebo Then Calcitriol 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg
Overall Study STARTED	12	12
Overall Study Completed First Leg of Crossover	8	10
Overall Study COMPLETED	8	10
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Calcitriol Then Placebo 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg	Placebo Then Calcitriol 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	1	0
Overall Study PET Equipment Related	2	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Participants n=24 Participants Baseline characteristics of all participants prior to group order randomization.
Age, Continuous	31.96 years STANDARD_DEVIATION 6.58 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants

PRIMARY outcome

Timeframe: day 1

Population: Participants required complete imaging data (i.e., 4/4 completed PET scans and a completed MRI) in order to be included in analysis. Thus, only n = 18 participants were analyzed to assess BPND.

Outcome measures

Outcome measures
Measure	Calcitriol n=8 Participants 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg	Placebo n=10 Participants 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. 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 PHNO: Used as a tracer for in vivo imaging. Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg
Non-displaceable Tracer Binding Potentials Region of interest: Ventral Striatum	2.93 ratio Standard Deviation 0.63	2.91 ratio Standard Deviation 0.32
Non-displaceable Tracer Binding Potentials Region of interest: Caudate	1.50 ratio Standard Deviation 0.30	1.50 ratio Standard Deviation 0.19
Non-displaceable Tracer Binding Potentials Region of interest: Putamen	2.21 ratio Standard Deviation 0.47	2.21 ratio Standard Deviation 0.26
Non-displaceable Tracer Binding Potentials Region of interest: Substantia Nigra/Ventral Tegmental Area	0.92 ratio Standard Deviation 0.30	1.01 ratio Standard Deviation 0.24

PRIMARY outcome

Timeframe: day 7

Outcome measures

Outcome measures
Measure	Calcitriol n=10 Participants 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg	Placebo n=8 Participants 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. 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 PHNO: Used as a tracer for in vivo imaging. Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg
Non-displaceable Tracer Binding Potentials Region of interest: Ventral Striatum	2.91 ratio Standard Deviation 0.32	3.05 ratio Standard Deviation 0.66
Non-displaceable Tracer Binding Potentials Region of interest: Caudate	1.52 ratio Standard Deviation 0.21	1.59 ratio Standard Deviation 0.30
Non-displaceable Tracer Binding Potentials Region of interest: Putamen	2.31 ratio Standard Deviation 0.28	2.38 ratio Standard Deviation 0.47
Non-displaceable Tracer Binding Potentials Region of interest: Substantia Nigra/Ventral Tegmental Area	1.08 ratio Standard Deviation 0.25	1.07 ratio Standard Deviation 0.31

SECONDARY outcome

Timeframe: day 1

Population: All participants completed both study arms

In this computer based test, subjects are shown a random sequence of numbers (2-digit, 3-digit, and 4-digit) and are instructed to press a button as quickly and accurately as possible (with their preferred hand) when a number repeats. Subjects are instructed to withhold their response for any other sequence of numbers. The measure is presented as dprime, which is calculated: d' = z(H) - z(F), where z(H) is the z-score of the hit rate and z(F) is the z-score of the false positive rate. A z-score of 0 represents the population mean. d' is indicates better performance on the task with higher values, z(H) indicates better performance on the task with higher values due to higher hit rate, and z(F) indicates worse performance on the task with higher values due to higher false positive rates.

Outcome measures

Outcome measures
Measure	Calcitriol n=8 Participants 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg	Placebo n=10 Participants 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. 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 PHNO: Used as a tracer for in vivo imaging. Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg
Continuous Performance Task (CPT-IP)	3.03 z-score Standard Deviation 0.74	3.35 z-score Standard Deviation 1.22

SECONDARY outcome

Timeframe: day 7

Population: All participants completed both study arms.

Outcome measures

Outcome measures
Measure	Calcitriol n=10 Participants 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg	Placebo n=8 Participants 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. 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 PHNO: Used as a tracer for in vivo imaging. Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg
Continuous Performance Task (CPT-IP)	3.03 z score Standard Deviation 0.74	3.22 z score Standard Deviation 0.42

Adverse Events

Calcitriol Then Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo Then Calcitriol

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Calcitriol Then Placebo n=12 participants at risk 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg	Placebo Then Calcitriol n=12 participants at risk 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. 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 PHNO: Used as a tracer for in vivo imaging. calcitriol: three 0.5 mcg capsules Placebo oral capsule: three 0.5 mcg capsules high-resolution research tomography: A functional imaging technique that is used to observe metabolic processes in the body. Dextro Amphetamine: Dexedrine 0.3 mg/kg, to a maximum dose of 30 mg
Gastrointestinal disorders Mild transient nausea	33.3% 4/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.	33.3% 4/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.
Psychiatric disorders Mild anxiety	8.3% 1/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.	0.00% 0/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.
General disorders Mild insomnia	16.7% 2/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.	16.7% 2/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.
Gastrointestinal disorders Nausea and vomiting	16.7% 2/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.	0.00% 0/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.
Nervous system disorders Loss of consciousness	8.3% 1/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.	0.00% 0/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.
Cardiac disorders Asymptomatic non-exclusionary bradycardia	0.00% 0/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.	8.3% 1/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.
Vascular disorders Hypertension, asymptomatic and non-exclusionary	8.3% 1/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.	0.00% 0/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.
Infections and infestations Throat irritation	8.3% 1/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.	0.00% 0/12 • Up to 14 days Adverse events were collected at the individual level and were not distinguished at the stage of the crossover.

Additional Information

Marc Potenza, PhD, MD

Yale School of Medicine

Phone: (203) 974-7356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place