Oxytocin Treatment of Alcohol Dependence
Oxytocin Treatment of Alcohol Dependence
Purpose: Test whether oxytocin treatment decreases drinking in people who have been consuming
 alcohol heavily for long periods and are physically and psychologically dependent on alcohol.

 Participants: 50 adults with alcohol dependence

 Procedures (methods): Oxytocin or placebo will be administered three times a day for the
 first 2 days followed by twice daily intranasal doses for the rest of the 12 weeks. Before,
 during and at the end of the trial, each subject will undergo evaluations including
 breathalyzer readings, rating withdrawal symptoms, interviews about amount of alcohol
 consumed since last clinic visit, subject self-ratings of anxiety, alcohol craving and, at
 some visits, laboratory measures (blood and urine) to monitor safety and alcohol/drug use.
 Following the active phase of the trial, subjects will be followed up at 4 weeks and 12 weeks
 to evaluate for post-medication safety and efficacy
The purpose of this research study is to learn whether oxytocin treatment decreases drinking
 and alcohol craving in people who have been consuming alcohol heavily for long periods and
 are unable to stop drinking on their own. Oxytocin is made naturally and is released in parts
 of the brain where it acts like a chemical signal from one cell to another. Oxytocin is
 approved by the Food and Drug Administration for stimulating labor in pregnant women but is
 not approved as a treatment to decrease alcohol drinking.

 People who drink large amounts of alcohol every day or many days per week for weeks or months
 undergo chemical changes in their brains. They continue to drink frequently and heavily
 because, even though they may know drinking is not good for their health, they experience
 unpleasant symptoms if they stop or decrease drinking. Those symptoms can include increased
 anxiety, difficulty sleeping, difficulty tolerating stress, mild to moderate withdrawal
 symptoms such as tremors, nausea, feeling sweaty and/or headaches, and cravings to drink.
 Studies found that giving oxytocin to alcohol-addicted animals reduced symptoms when they
 were put into alcohol withdrawal. A pilot study conducted at UNC found that twice daily
 intranasal doses of oxytocin decreased withdrawal symptoms in heavy drinkers who were
 admitted to a hospital for medical detoxification to come off alcohol.

 This study will test whether daily intranasal oxytocin treatment for 12 weeks will decrease
 how much subjects drink as well as craving for alcohol and anxiety.

 Prospective subjects must have been drinking large amounts of alcohol for a sustained period
 to qualify for this study and want help to stop or cut back on their drinking. Subjects will
 self-administer oxytocin or placebo in this study in an intranasal spray. The placebo spray
 contains all of the ingredients of the oxytocin spray EXCEPT oxytocin. Subjects' assignment
 to oxytocin or placebo treatment will be random (like a flip of a coin).

 Subjects must sign a consent form to take part in this study. Their participation in the
 study will last up to 14-15 weeks. Prospective subjects will be recruited from the community
 through advertisements (radio, social media, mass emails, etc). Those who respond to
 advertisements will undergo initial screening over the phone. Prospective subjects who appear
 to meet study criteria based on the phone screen will give informed consent and undergo more
 detailed evaluation during a screening clinic visit. If they are found to meet study
 criteria, they will shortly thereafter attend another clinic visit (randomization clinic
 visit) during which they will be randomized to oxytocin or placebo treatment and take their
 first test dose under study personnel supervision. They will then take home the bottle
 contained the intranasal study medication to which they have been randomized and
 self-administer intranasal test doses at home for the remainder of the 12-week test treatment
 period. New intranasal spray bottles will be exchanged for old every 2 weeks. Subjects will
 attend 8 additional clinic visits over a 12 week period after the randomization clinic visit.
 Each clinic visit will last 1-2 hours.

 Procedures during screening clinic visits will include: 1) a Breathalyzer test (a reading of
 zero is necessary for subjects to give informed consent); 2) vital sign measures and a CIWA
 (Clinical Institute Withdrawal Assessment for Alcohol) scale score (subjects must not be in
 significant withdrawal when they give informed consent and undergo screening evaluations); 3)
 urine collection to test for addictive substances and pregnancy; 4) completion of the Time
 Line Follow Back (TLFB) interview to determine how many standard drinks have been consumed
 during the previous 90 days; 5) interview using the Structured Clinical Interview for DSM-IV
 (SCID). Alcohol use module to confirm subjects meet DSM-IV TR criteria for alcohol
 dependence; 6) completion of the MINI International Neuropsychiatic Interview (MINI)
 diagnostic sections on substance use disorders, psychotic disorders, bipolar disorder, and
 eating disorders; 7) subject completion of the Penn Alcohol Craving Scale (PACS); 8) subject
 completion of the Spielberger State-Trait Anxiety Inventory (SSTAI); 9) physical examination
 by a study doctor; 10) blood collection for laboratory tests.

 During the randomization clinic visit, subjects who screen into the study will be randomly
 assigned (like the flip of a coin) to receive either oxytocin or placebo intranasal spray.
 Members of the researcher staff will instruct subjects in how to self-administer intranasal
 spray doses from a spray bottle. Subjects will then take their first intranasal test dose
 during a clinic visit scheduled shortly after this screening visit. Subjects will take an
 intranasal spray bottle home with them after this visit and continue to self-administer
 intranasal test doses three time each day (at approximately breakfast, lunch and dinner time)
 for two days and thereafter will take intranasal test doses twice each day (at approximately
 breakfast and dinner time). Each dose will be 10 sprays into their nose (5 per nostril
 alternating between nostrils).

 Procedures during subsequent outpatient clinic visits will include: 1) a Breathalyzer
 reading; 2) vital signs and a CIWA score; 3) a TLFB interview; 4) PACS self-rating; 5) State
 portion of the SSTAI (SSAI) self-rating; 6) at the week 4, 8, and 12 clinic visits, blood and
 urine collection for laboratory tests, pregnancy tests and addictive drug screens.

 During the randomization clinic visit and each subsequent clinic visit, subjects'
 Breathalyzer reading must be less than .04 g/dL for study procedures to be done. If
 Breathalyzer readings are higher, the visit will be rescheduled. Also, during each of these
 clinic visits, a Medical Management session (special talk therapy for alcohol dependence)
 will be conducted with the study doctor before patients are discharged.
Inclusion Criteria:

 -  Meeting criteria for DSM-IV-TR alcohol dependence.

 -  Consumption of at least 35 standard drinks/week for men or 28 standard drinks/week for
 women for at least 4 consecutive weeks prior to enrollment into the study.

 -  Women who are able to conceive children and who are sexually active must be on an
 effective form of birth control such as oral contraceptives, IUDs or the use of
 condoms with spermicide.

 -  Competency to give valid informed consent as indicated by a) a Breathalyzer reading at
 the time the consent form is signed showing an estimated blood alcohol level (BAL) of
 zero; b) ability to understand the written informed consent form demonstrated by
 correctly answering questions about the contents of the form after reading the consent
 form without help (this will also determine whether prospective subjects can read and
 understand the study questionnaires).

 -  Ability to get to appointments either through personal or public transportation.

 -  Ages 18-65.

 Exclusion Criteria:

 -  History of alcohol withdrawal-related seizures, delirium tremens or hallucinations.

 -  Clinically significant medical disease that might interfere with the evaluation of the
 study medication or present a safety concern (e.g., renal insufficiency, cirrhosis,
 unstable hypertension, unstable diabetes mellitus, seizure disorder).

 -  History of psychotic disorder or admission for mania, meeting criteria for an eating
 disorder in the last 2 years, current moderate or severe major depression, current
 suicidal ideation.

 -  Currently meeting DSM-IV TR criteria for dependence on addictive substances other than
 alcohol except for nicotine or caffeine. Substance abuse disorders are not
 exclusionary.

 -  Consumption during the week prior to enrollment or plans to consume during the 12-week
 trial of benzodiazepines, barbiturates, anticonvulsants or stimulants.

 -  AST or ALT > 5 times ULN, bilirubin > 1.5 X ULN, sodium < 132 or > 150 mMol/L,
 potassium < 3.2 or > 5.3 mMol/L.

 -  Women who are pregnant or breastfeeding.

 -  Currently participating in or intent to participate in an additional alcohol treatment
 program during the study period other than Alcoholics Anonymous.

 -  Court-mandated participation in alcohol treatment or pending incarceration.