Vitamin D and Cocaine Administration

NCT04826133 | Terminated Early Phase 1 FDA Drug

• 1 other identifier: 2000025367
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cocaine Use Disorder

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Probabilistic Selection Task (PST)

  15 minutes

• Probabilistic Reward Task (PRT)

  15 minutes

• Subjective Effects of Cocaine / Visual Analog Scale (VAS)

  150 minutes

Study Arms (2)

Acute Pretreatment with Calcitriol

ACTIVE COMPARATOR

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

Acute Pretreatment with Placebo

PLACEBO COMPARATOR

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

Interventions

Calcitriol DRUG

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.

Also known as: 1,25-dihydroxyvitamin D3

Acute Pretreatment with Calcitriol

Placebo OTHER

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.

Acute Pretreatment with Placebo

Eligibility Criteria

• Age: 30 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Interventions

Calcitriol

Intervention Hierarchy (Ancestors)

Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Marc Potenza, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 1, 2021
• Study Start: March 27, 2019
• Primary Completion: January 17, 2020
• Study Completion: January 17, 2020
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

US (1)