Vitamin D in OUD: Exploration of Alterations on the Dopamine D2/D3 Receptor System

NCT06261905 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2000036908000
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Opioid Use Disorder

Keywords

Vitamin D

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Two 120-minute scans, at least 6 days apart between study conditions.

Secondary Outcomes (3)

• Spontaneous Blink Rate (SBR)

  Two 5-minute tasks, at least 6 days apart between study conditions.

• Continuous Performance Task - Identical Pairs (CPT-IP)

  Two 10-minute tasks, at least 6 days apart between study conditions.

• Probabilistic Reversal Learning Task (PRLT)

  Two 10-minute tasks, at least 6 days apart between study conditions.

Study Arms (2)

Calcitriol

ACTIVE COMPARATOR

Subjects with OUD will receive a baseline MRI. On the night before and day of testing, subjects with OUD will receive two doses of calcitriol (3.0mcg total), followed by PHNO injection and PET Scan for the calcitriol condition. All subjects will complete the study with both active calcitriol and a placebo control and the order these interventions are received will be randomized.

Drug: [11C]-PHNO; Dietary Supplement: Calcitriol; Procedure: PET Scan

Placebo

PLACEBO COMPARATOR

Subjects with OUD will receive a baseline MRI. On the night before and day of testing, subjects with OUD will receive two doses of an inactive placebo, followed by PHNO injection and PET Scan for the placebo condition. All subjects will complete the study with both active calcitriol and a placebo control and the order these interventions are received will be randomized.

Drug: [11C]-PHNO; Other: Placebo Control; Procedure: PET Scan

Interventions

[11C]-PHNO DRUG

PHNO is used as a tracer for in-vivo imaging.

Also known as: PHNO

Calcitriol; Placebo

Calcitriol DIETARY_SUPPLEMENT

Calcitriol is an active form of Vitamin D and is given in 3 0.5mcg capsules per dose.

Also known as: Vitamin D

Calcitriol

Placebo Control OTHER

A placebo is an inert capsule, which contains no active ingredients. The placebo will be given in 3 0.5mcg capsules per dose.

Placebo

PET Scan PROCEDURE

A high resolution PET Scan performed using a NeurExplorer CT scanner.

Calcitriol; Placebo

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
• Meets the criteria for OUD, as determined by the Structured Clinical Interview for DSM-5 (SCID)
• Stable and receiving buprenorphine treatment for OUD
• For females, non-lactating, with a negative serum or urine pregnancy (hCG) 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 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, sedative hypnotics), except for nicotine and opiates.
• A primary major DSM-5 psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, etc.) as determined by the SCID, except for Opioid Use Disorder and related conditions.
• 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 the study physician's review of both the questionnaire responses and screening ECG. If there is concern for the subject's safety due to these assessments, research staff will consult a Yale PET Center affiliated cardiologist prior to including the subject for the study.
• Current use of psychotropic and/or potentially psychoactive prescription medications
• Receiving medications for OUD other than buprenorphine (e.g., methadone treatment)
• For females, laboratory (β-HCG) or physical evidence of pregnancy/lactation
• 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 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 12 ng/ml.
• Morbid obesity i.e., BMI over 35 (more prone to lower vitamin D levels)

Sponsors & Collaborators

• Yale University: lead
• University of Pennsylvania: collaborator

Study Sites (1)

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

naxagolide; Calcitriol; Vitamin D; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Secosteroids; Membrane Lipids; Lipids; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Marc Potenza, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

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 primarily a within-subject, two scan, randomized, double-blind, placebo-controlled study design. Healthy control subjects will only complete one scan to serve as a baseline comparison for subjects with OUD.

Study Record Dates

• First Submitted: February 7, 2024
• First Posted: February 15, 2024
• Study Start: March 13, 2024
• Primary Completion: February 18, 2025
• Study Completion: February 18, 2025
• Last Updated: November 14, 2025

Record last verified: 2025-11

Locations

US (1)