Vitamin D and Cocaine Administration

Testing Restoring Effects of Vitamin D on the Dopamine System: A Human Laboratory Study Among Cocaine Users.

This study is designed to explore the effects of acute pre-treatment with 1,25-dihydroxyvitamin D3 (calcitriol), as compared to placebo on the behavioral (e.g., attempts to self-administer and ultimate number of infusions/boluses of cocaine self-administered), neurocognitive (e.g., performance on computerized tests of reward related learning such as the probabilistic selection task or PST and probabilistic reward task or PRT), and subjective effects (e.g, computerized visual analog scale [VAS] ratings of euphoria/, craving, etc.) of cocaine in experienced, non-treatment seeking users of the drug.

Study Overview

• Status: Terminated
• Conditions: Cocaine Use Disorder
• Intervention / Treatment: Drug: Calcitriol; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Connecticut Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 51 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 30-55 years
• Voluntary, written, informed consent
• Physically healthy by medical history, physical, neurological, ECG and laboratory examinations
• DSM-5 criteria for at least moderate Cocaine Use Disorder
• Recent street cocaine use in excess of quantities used in the current study
• Intravenous and/or smoked (crack/ freebase) use
• Positive urine toxicology screen for cocaine
• Laboratory evidence of vitamin D sufficiency (i.e., 25(OH)-vitamin D3 level ≥ 20/mg)
• For females, a negative serum pregnancy (HCG) test at screening and admission, and a negative urine pregnancy test (HCG) on cocaine administration days.

Exclusion Criteria:

• A history of other substance dependence (except for nicotine). Positive urine toxicology for cannabis is accepted for the study unless there is evidence for dependence per Structured Clinical Interview for DSM-5 (SCID) interview. Positive urine toxicology for other drugs at screening will be repeated. If positive again and/or positive at admission, subjects will be excluded
• < 1 year of cocaine abuse/dependence
• A primary DSM-5 Axis I major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, etc.) unrelated to cocaine as determined by the SCID-5
• Medical comorbidities including serum calcium ( > 10.5 mg/dl, serum phosphorus > 4.2 mg/dl), hyperparathyroidism, kidney disease (e.g., Serum creatinine > 1.3 mg/dl)
• A history of significant and uncontrolled medical (e.g., cardiovascular, diabetic/metabolic) or neurological (e.g., cerebrovascular, seizures, traumatic brain injury) illness
• A history of seizures
• Current use of psychotropic/potentially psychoactive medications or medications that can have drug drug interactions with calcitriol, including over the counter Vitamin D products, thiazide diuretics, and calcium supplements, etc, as referenced in the package insert for calcitriol
• Seeking treatment for drug abuse/dependence
• Hypersensitivity to calcitriol
• For females, physical or laboratory (HCG) evidence of pregnancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Acute Pretreatment with Calcitriol; To explore the effects of acute pre-treatment with Calcitriol on attempts to self-administer and ultimate number of infusions/boluses of cocaine, in experienced, non treatment-seeking users of the drug	Drug: Calcitriol; Subjects will receive an oral administration of calcitriol (1,25-dihydroxyvitamin D3) 1.5 μg (three capsules of 0.5 μg each) at 9 pm, night before each cocaine session, and at 8 am, morning of each cocaine session. This dose of calcitriol is lower than doses safely administered in other human studies and for a duration of time shorter than doses safely administered in other trials. In addition, this dose has been already tested by our group, subject of a different grant application, and should be effective at enhancing stimulant's induced dopamine release, in comparison to placebo.; Other Names: 1,25-dihydroxyvitamin D3
Placebo Comparator: Acute Pretreatment with Placebo; To explore the effects of acute pre-treatment with placebo on attempts to self-administer and ultimate number of infusions/boluses of cocaine, in experienced, non treatment-seeking users of the drug	Other: Placebo; Subjects will receive an oral administration of three capsules of placebo at 9 pm the night before each cocaine session, and at 8 am, morning of each cocaine session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cocaine Self Administration Attempts	Number of attempts to self administer cocaine will be analyzed.	90 minutes
Cocaine Self Administration Infusions	Number of infusions of cocaine will be analyzed.	90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probabilistic Selection Task (PST)	The Probabilistic Selection Task (PST) is a computerized task that assesses the tendency to learn from positive versus negative outcomes. PST will be analyzed using linear mixed models with treatment and time included as a within subjects variable.	15 minutes
Probabilistic Reward Task (PRT)	The Probabilistic Reward Task (PRT) is a computerized task that uses an asymmetric reinforcement schedule to produce a response bias towards the more frequently rewarded of two possible stimuli. PRT will be analyzed using linear mixed models with treatment and time included as a within subjects variable.	15 minutes
Subjective Effects of Cocaine / Visual Analog Scale (VAS)	During cocaine sessions, subjects will complete a series of self rated subjective effects measuring how they feel on cocaine, using a scale of 0 (not at all) to 10 (most ever). VAS ratings will focus on euphoria ("high") as a primary outcome, however, other positive, negative, psychomotor, and drug-craving ratings (e.g. good, bad, stimulated, paranoid, hungry, etc.) will be collected as well. Ratings are implemented on a touch-screen laptop computer and presented every 5 minutes, throughout the session	150 minutes

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2019
• Primary Completion (Actual): January 17, 2020
• Study Completion (Actual): January 17, 2020

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: March 30, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

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; Dihydroxycholecalciferols
• Other Study ID Numbers: 2000025367

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No