Clinical trial NCT02251912
Conditions: Alcohol Dependence
Keywords: Alcohol dependence Alcohol Oxytocin Intranasal administration
Sponsor: University of North Carolina, Chapel Hill
Start date: 2015-07-01; Completion date: 2016-09-01
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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

Detailed description:
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.

Arms: arm 1: Intranasal oxytocin doses 2-3 times/day for 12 weeks arm 2: Intranasal placebo doses 2-3 times/day for 12 weeks
Interventions: intervention 1: Intranasal Oxytocin intervention 2: Placebo
Intervention descriptions: intervention 1: 10 insufflations (40IU of oxytocin total) given 3 initially then 2 times daily for 12 weeks intervention 2: 10 insufflations (same solution as active treatment minus oxytocin) given 3 initially and then 2 times daily for 12 weeks

Protocol documents: