The research team is investigating Opioid Use Disorder (OUD), a disorder characterized by dysregulated dopaminergic tone, to evaluate the mechanisms of adjunctive treatment with calcitriol. The investigators will recruit 12 subjects with OUD and 12 healthy subjects to participate in a double-blind, randomized study design where subjects will complete up to 2 Positron Emission Tomography (PET) scans using \[11C\]-PHNO. The investigators will compare subjects in differences between their own study days and in differences between healthy control subjects and subjects with OUD.
Previous research has indicated that Dopamine (DA) may play a role in withdrawal and dependence in Opioid Use Disorder (OUD). The present study will investigate dopamine receptor availability in 12 subjects with OUD compared with 12 HC subjects using \[11C\](+)-PHNO and the impact of calcitriol on these receptors. Research has indicated that a common feature in substance use disorders (SUD) is a hypo-dopaminergic state. Further, preclinical and observational research has pointed to a possible benefit of calcitriol in individuals who have OUD and our research group has previously shown the potential benefits of calcitriol on addressing this hypo-dopaminergic state. If successful, the results of this research study may improve the standard treatment for OUD through calcitriol supplementation. Specifically, the present study seeks to address the following aims: Specific Aim 1: As part of a between-subject study design, to determine whether acute calcitriol (vs. placebo) administration is associated with greater dopamine (DA) release in the caudate, putamen, ventral striatum (VST), and substantia nigra / ventral tegmental area (SN/VTA) of subjects with OUD compared to healthy control subjects (HCs). Specific Aim 2: As part of a within-subject, two-day study design, to determine whether acute calcitriol (vs. placebo) administration is associated with greater dopamine (DA) release in the caudate, putamen, ventral striatum (VST), and substantia nigra / ventral tegmental area (SN/VTA) of subjects with OUD. Specific Aim 3: To determine whether acute calcitriol (vs. placebo) administration is associated with higher spontaneous eyeblink rate, a non-PET indicator of higher dopamine activity, among subjects with OUD. Specific Aim 4: To determine whether acute calcitriol (vs. placebo) administration is associated with better performance on neurocognitive measures (e.g., the Continuous Performance Task or CPT-IP and the Probabilistic Reversal Learning Task or PRLT) among subjects with OUD.
Study Type
INTERVENTIONAL
PHNO is used as a tracer for in-vivo imaging.
Calcitriol is an active form of Vitamin D and is given in 3 0.5mcg capsules per dose.
A placebo is an inert capsule, which contains no active ingredients. The placebo will be given in 3 0.5mcg capsules per dose.
Yale School of Medicine
New Haven, Connecticut, United States
Non-displaceable Tracer Binding Potentials (BPND)
BPND is a metric that assesses the level of dopamine activity in a priori regions of interest. For Specific Aim 1, the investigators plan to assess the differences in baseline BPND in dopamine D2/D3 receptors between healthy control subjects and the baseline placebo-controlled scan for subjects with OUD.
Time frame: One 120-minute scan.
Non-displaceable Tracer Binding Potentials (BPND)
BPND is a metric that assesses the level of dopamine activity in a priori regions of interest. For Specific Aim 2, the investigators plan to assess the differences in BPND in dopamine D2/D3 receptors within subjects who have OUD. The investigators will compare BPND on the placebo-controlled experimental day and BPND on the active calcitriol experimental day.
Time frame: Two 120-minute scans, at least 6 days apart between study conditions.
Spontaneous Blink Rate (SBR)
SBR is a metric that may assess levels of dopamine activity, without requiring the subject to undergo a PET scan. Subjects will be recorded for approximately 5 minutes to assess blink rate during each experimental day to address Specific Aim 3.
Time frame: Two 5-minute tasks, at least 6 days apart between study conditions.
Continuous Performance Task - Identical Pairs (CPT-IP)
The CPT-IP is a computer based test where 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. Subjects will complete this task on each experimental day to address Specific Aim 4.
Time frame: Two 10-minute tasks, at least 6 days apart between study conditions.
Probabilistic Reversal Learning Task (PRLT)
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Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
5
A high resolution PET Scan performed using a NeurExplorer CT scanner.
The PRLT is a computer based test where subjects are instructed to select a card from three randomly sorted piles and are asked to try to maximize their score in the task. Subjects will complete this task on each experimental day to address Specific Aim 4.
Time frame: Two 10-minute tasks, at least 6 days apart between study conditions.