Oxytocin Treatment for Alcohol Use Disorders

NCT03636555 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 18-1758R01AA025942-01A1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

To further test the effectiveness of oxytocin in heavy drinkers, half of the cohort in the proposed study will meet criteria for heavy drinking (\>35 standard drinks/week \[men\], \>28 standard drinks/week \[women\] for at least 4 consecutive weeks). However, the investigators think it important to expand the cohort of the proposed study to include subjects with moderate Alcohol Use Disorder (AUD) who meet lower drinking criteria so the outcome of the study will be relevant to a larger percentage of individuals who have AUD. The lower drinking criteria will be minimum of 14 drinks/week (women) or 21 drinks/week (men) with an average of at least two heavy drinking days (≥5 standard drinks for men and ≥4 standard drinks for women) each week in the 4-week period prior to screening. As in the R21-funded Preliminary Study, individuals recruited from the community who meet study criteria based on assessment during a screening clinic visit will be randomized to twice a day (BID) intranasal oxytocin or intranasal placebo during a subsequent clinic visit. After instruction by research staff during the randomization clinic visit, subjects will self-administer intranasal treatments from blind-labeled spray bottles that they take home. During clinic visits at 1, 2, 3, 4, 6, 8, 10, and 12 weeks after randomization, drinking since the last visit will be quantified and other measures summarized above will be obtained. Subjects will self-administer test intranasal treatments for 12 weeks. Drinking will also be quantified during clinic visits at 6 and 12 weeks after cessation of intranasal treatments. This clinical trial will be the first adequately powered, double blind, placebo-controlled trial examining the efficacy and tolerability of BID intranasal oxytocin (40 IU/dose; 80 IU/d) on alcohol drinking in AUD. The trial will also be the first to prospectively examine the effects of intranasal oxytocin on anxiety symptoms in individuals with AUD.

Conditions

Alcohol Use Disorder

Keywords

Oxytocin; Heavy drinking; Moderate drinking

Outcome Measures

Primary Outcomes (2)

• Mean heavy drinking days

  A heavy drinking day is defined by consumption of 5 (men) or 4 (women) standard drinks or more during a day

  24 weeks

• Mean drinks per drinking day

  The average number of standard drinks consumed on days when subjects drink alcohol drinks

  24 weeks

Study Arms (2)

Oxytocin

ACTIVE COMPARATOR

Syntocinon Spray (intranasal oxytocin spray). Each dose is 10 intranasal insufflations totaling 1.0 mL of Syntocinon Spray containing 40 IU of oxytocin. Subjects self-administer doses twice daily (before breakfast and before dinner) for 12 consecutive weeks.

Drug: Oxytocin

Placebo

PLACEBO COMPARATOR

Each dose is 10 intranasal insufflations totaling 1.0 mL of a solution containing all ingredients in Syntocinon Spray except oxytocin. Subjects self-administer doses twice daily (before breakfast and before dinner) for 12 consecutive weeks.

Drug: Placebo

Interventions

Oxytocin DRUG

Oxytocin will be given in an intranasal spray (Syntocinon Spray) twice daily (10 insufflations, 1.0 mL, 40 IU/dose) for 12 weeks

Also known as: Syntocinon

Oxytocin

Placebo DRUG

Placebo solution (contained all the ingredients in Syntocinon Spray except for oxytocin) will be given as an intranasal spray twice daily (10 insufflations, 1.0 mL/dose) for 12 weeks

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women between the ages of 21 and 65. Children, ages less than 21 years, and adults over 65 years will not be studied because of the lack of safety data on the use of oxytocin in these age ranges.
• All subjects must meet DSM-V criteria for moderate or severe alcohol use disorder. In addition the investigators will recruit 50% of individuals (evenly distributed between men and women) who meet criteria for heavy drinking: \> 28 standard drinks/week (women) or \>35 drinks/week (men) in the 30-day period prior to screening. Those not meeting heavy drinking criteria will be required to have a minimum of 14 drinks/week (women) or 21 drinks/week (men) with an average of at least two heavy drinking days (≥5 standard drinks for men and ≥4 standard drinks for women) per week in the 30 day period prior to screening
• Ability to understand and sign written informed consent.
• Must have a 0.0 gms/dL breathalyzer reading on the day of screening and \< 0.4 gms/dL on the day of randomization.
• Express a desire to achieve abstinence or to greatly reduce alcohol consumption
• Must have a stable residence and be able to identify an individual who could contact participant if needed.

You may not qualify if:

• Clinically significant medical disease that might interfere with the evaluation of the study medication or present a safety concern (e.g., cirrhosis, unstable hypertension, unstable diabetes mellitus). Clinically significant psychiatric illness including any psychotic disorder, bipolar disorder, severe depression, or suicidal ideation.
• Substance use disorder other than nicotine use disorder or mild cannabis use disorder. Occasional use of cocaine is acceptable.
• Concurrent use of any psychotropic medication including, mood stabilizers, antipsychotics, anxiolytics, stimulants, or hypnotics with the exception of stable doses of antidepressants for one month.
• Prior history of adverse reaction to oxytocin.
• Serum sodium concentration \< 134 mEq/L.
• Creatinine level \> 1.5 times Upper Limit of Normal (ULN) or Estimated Glomerular Filtration Rate \< 50.
• AST, or ALT \> 5 times ULN or bilirubin \> 1.5 X ULN.
• Positive urine toxicology screen with the exception of cannabis. Individuals with positive cannabis screens will be excluded only if they have a history of moderate/severe cannabis use disorder.
• Pregnant women and women of childbearing potential who do not practice a medically acceptable form of birth control (oral or depot contraceptive, or barrier methods such as diaphragm or condom with spermicidal).
• Women who are breastfeeding.
• Individuals requiring inpatient treatment or more intense outpatient treatment for their alcohol dependence.
• Participation in any clinical trial within the past 60 days.
• Court-mandated participation in alcohol treatment or pending incarceration.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Cort Pedersen

Durham, North Carolina, 27712, United States

Location

Related Publications (12)

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MeSH Terms

Conditions

Alcoholism

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

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

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

• Cort Pedersen, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: UNC Hospitals Investigational Drug Service blind labels intranasal spray bottles containing oxytocin or placebo spray and dispenses bottles based on a randomization scheme provided by the study Biostatistician
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blind, placebo-controlled trial

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 17, 2018
• Study Start: October 1, 2019
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: November 13, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 9 to 36 months following publication
• Access Criteria: The investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Locations

US (1)