Oxytocin in Alcohol Use Disorder

NCT02711189 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 16008216-AA-0082
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Oxytocin is a naturally occurring substance in the body. Studies show that oxytocin may affect how the body responds to alcohol. Researchers believe oxytocin may be a possible treatment for alcoholism. Objective: To test whether the hormone oxytocin affects the brain reward system. To see if it affects how people respond to alcohol and other rewarding things in life like food and seeing loved ones. Eligibility: Men ages 21-55 who have an alcohol use disorder. Design: Participants will have two 6-day inpatient study visits. They will have:

• Study medication or placebo given twice daily as a nasal spray.
• Height and weight measured.
• Medical history.
• Blood and urine tests.
• Breath tested for alcohol.
• Electrocardiogram.
• An alcohol administration session. In a bar-like room, where participants will consume four alcoholic drinks.
• Magnetic resonance imaging (MRI). The MRI scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder. A device called a coil will be placed over their head. Participants will complete tasks on a computer screen.
• In another alcohol session. they will drink an alcoholic beverage then answer questions. Participants will get a tab for eight more drinks ($3.00 per drink). They may drink any of the drinks or take the money. Participants will hold and smell a glass of water and their favorite alcoholic drink.
• Heart rate and blood pressure will be monitored.
• Saliva samples will be collected
• Computer tasks and questionnaires. About one week after the end of visit 2, participants will return to clinic for a follow-up visit. Symptoms and side effects will be evaluated.

Conditions

Alcoholism

Keywords

Addiction; Oxytocin; Functional Magnetic Resonance Imaging (fMRI); Alcohol; Cue Reactivity

Outcome Measures

Primary Outcomes (3)

• Alcohol Craving, Self-Administration

  Ongoing

• Stimulation Sedation; Cognitive Performance

  Ongoing

• BOLD response cognitive tasks and cues

  Ongoing

Study Arms (2)

Oxytocin

ACTIVE COMPARATOR

Intranasal oxytocin will be delivered on twice daily basis in this crossover trial.

Drug: Oxytocin

Placebo

PLACEBO COMPARATOR

Within Subject Design

Other: Placebo

Interventions

Oxytocin DRUG

Oxytocin nasal spray given in dose 80

Oxytocin

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• year old male subjects. Justification: women will not be included due to: 1) the confound of the estrogen-modulating effect of OT; 2) the need to control for menstrual cycle phase across repeated days of study procedures which would significantly limit the feasibility of the study
• Must meet DSM-5 criteria for AUD based on the SCID
• Right handed

You may not qualify if:

• Non-drinkers (alcohol-naive individuals or current abstainers).
• Currently seeking treatment to reduce or stop alcohol use.
• Current diagnosis of substance use disorder other than nicotine as determined by DSM-5.
• Current clinically significant major depression or anxiety; or lifetime diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or obsessive compulsive disorder.
• Lifetime history of suicide attempts.
• Contraindications for MRI scanning, including metal in body that are contraindicated for MRI (such as implants, pacemaker, prostheses, shrapnel, irremovable piercings), left-handedness, claustrophobia or unable to lie comfortably supine for up to 2 hours in the and MRI scanner as determined from history and physician examination and the MRI safety form.
• BMI\>40 or if Investigators determine that subject s body shape precludes acquisition of an adequate MRI scan.
• Unable to provide a negative urine drug test (UDT).
• Medical contraindications: Current clinically significant disease, including CNS, seizures, cardiovascular, hypertension, arrhythmias, glaucoma, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders as determined by history and clinical exam at screening. Specifically, unstable hypertension, clinically significant EKG abnormalities, GFR rate \> 60ml/min, liver cirrhosis, AST or ALT \> 3X the upper normal limit, hemoglobin \< 10.5 g/dl.
• Participants who have significant alcohol withdrawal symptoms as defined by CIWA-Ar\>8.
• History of alcohol related seizures
• Requirement for or use in the past two weeks of psychoactive medications (four weeks for fluoxetine).
• Use of prescription or OTC medications known to interact with alcohol within 2 weeks of the study. These include, but may not be limited to: isosorbide, nitroglycerine, benzodiazepines, warfarin, anti-depressants such as amitriptyline, clomipramine and nefazodone, anti-diabetes medications such as glyburide, metformin and tolbutamide, H2-antagonists for heartburn such as cimetidine and ranitidine, muscle relaxants, anti-epileptics including phenytoin and phenobarbital codeine, and narcotics including darvocet, percocet and hydrocodone. Drugs known to inhibit or induce enzymes that metabolize alcohol should not be used for 4 weeks prior to the study. These include chlorzoxazone, isoniazid, metronidazole and disulfiram. Cough-and-cold preparations, which contain anti-histamines, pain medicines and anti-inflammatories such as aspirin, ibuprofen, acetaminophen, celecoxib and naproxen, should be withheld for at least 72 hours prior to each study session.
• History of hypersensitivity to oxytocin.
• Clinically significant electrolyte abnormalities, current rhinitis or use of vasoconstricting medications or prostaglandins

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Related Publications (2)

• Pedersen CA, Smedley KL, Leserman J, Jarskog LF, Rau SW, Kampov-Polevoi A, Casey RL, Fender T, Garbutt JC. Intranasal oxytocin blocks alcohol withdrawal in human subjects. Alcohol Clin Exp Res. 2013 Mar;37(3):484-9. doi: 10.1111/j.1530-0277.2012.01958.x. Epub 2012 Oct 1.

  PMID: 23025690 BACKGROUND

• McGregor IS, Bowen MT. Breaking the loop: oxytocin as a potential treatment for drug addiction. Horm Behav. 2012 Mar;61(3):331-9. doi: 10.1016/j.yhbeh.2011.12.001. Epub 2011 Dec 14.

  PMID: 22198308 BACKGROUND

MeSH Terms

Conditions

Alcoholism; Behavior, Addictive

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Compulsive Behavior; Impulsive Behavior; Behavior

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Mary R Lee, M.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 17, 2016
• Study Start: March 8, 2016
• Primary Completion: February 22, 2019
• Study Completion: February 22, 2019
• Last Updated: April 11, 2019

Record last verified: 2019-02-22