Oxytocin Treatment of Alcohol Dependence
Condition: Alcohol Withdrawal; Alcohol Dependence
MeSH terms: Alcoholism
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will test in individuals who have alcohol dependence (alcohol addiction) the
      hypotheses 1) that intranasal oxytocin treatment will decrease withdrawal symptoms during
      medical detoxification and 2) that intranasal oxytocin treatment for 12 weeks in the
      outpatient setting will decrease drinking.
    

Detailed description: 
      Study Design This is a randomized, double blind, placebo-controlled early phase II clinical
      trial.

      Recruitment: The study has 2 phases. The first is testing intranasal treatments (oxytocin
      [OT], placebo) on alcohol withdrawal (the inpatient phase) and the second is testing
      intranasal treatments on alcohol drinking, craving and anxiety over 12 weeks in the
      outpatient setting (the outpatient phase). Subjects for the inpatient phase will only be
      recruited from patients admitted to Freedom House (FRH, mental health center in Chapel Hill,
      NC) for medical detoxification from alcohol within the last 36 hours. Subjects for the
      outpatient phase of the study will be inpatients at FRH or the University of North Carolina
      (UNC) Hospitals who are near the end of their inpatient stay (medical detoxification has been
      or is nearly completed). Subjects in the inpatient phase of the study at FRH may continue
      into the outpatient phase after discharge. Subjects for the outpatient phase will also be
      heavy drinkers from the community who are screened during an initial outpatient clinic visit.

      Patients newly admitted to FRH to treat alcohol withdrawal will undergo a brief screening
      that includes: 1) a recent and past alcohol use interview (Time Line Follow Back, TLFB) and
      history of alcohol withdrawal interview; 2) a brief psychiatric interview; 3 ) a score on the
      10-item CIWA scale of alcohol withdrawal symptoms; 4) a review of potential medical exclusion
      criteria including a history of seizures or delirium tremens; 5) a spot urine pregnancy test
      on all prospective female subjects.

      Recruitment into the outpatient phase (treatment of outpatient drinking): Patients who
      undergo medical detoxification from alcohol will be recruited from FRH or from UNC Hospitals
      toward the end of their admission for participation in a trial to test the efficacy of
      intranasal OT vs. placebo treatment on alcohol drinking, alcohol craving and anxiety during a
      12-week outpatient treatment period. They will be screened to see if they meet study
      criteria. These individuals will read and sign the Breath Alcohol Policy that states that if
      their Breathalyzer reading at the beginning of an outpatient clinic visit is >.08 they will
      not be assessed at that visit and will not drive themselves home but rather will accept a
      ride from a family member, friend or a cab driver.

      Other individuals will be recruited from the community for participation in the outpatient
      phase of the study who have responded to a radio ad, a UNC listserve ad, a flyer, have been
      referred by local clinicians or have otherwise become aware of the study. These prospective
      subjects will undergo a telephone screening interview. If they appear to meet criteria over
      the phone, they will be further screened during an outpatient clinic visit. They must sign
      the Breath Alcohol Policy.

      Inpatient Treatment of Withdrawal Protocol and Measures: Subjects who enroll in the study
      shortly after being admitted to FRH will immediately complete the State portion of the
      Spielberger State-Trait Anxiety Inventory (SSTAI) and the Penn Alcohol Craving Scale (PACS).
      This will be followed by self-administration of their first intranasal test dose under
      supervision of research personnel. These subjects will self-administer additional intranasal
      test doses at 1 and 3 h after the initial dose and then on the evening of that first day of
      admission. On subsequent admission days at FRH, subjects will self-administer intranasal test
      doses 3 times per day. After the first intranasal test dose, blood (15 ml) and urine samples
      will be obtained from subjects at FRH by research personnel for complete blood count (CBC),
      electrolytes, blood urea nitrogen (BUN), creatinine, glucose, albumin, liver function tests,
      urinalysis and urine toxicology which will be transported to and run at the UNC Hospital
      laboratory.

      Between the 1st and 3rd initial intranasal test doses, research personnel will complete a
      more detailed psychiatric interview. Subjects will also complete the University of Rhode
      Island Change Assessment Scale to assess their stage of motivation to stop or cut back on
      their drinking, the Drinker's Inventory of Consequences to assess the spectrum of
      consequences related to drinking, the Family History of Alcoholism Module to assess family
      history of alcohol problems, the Patient Health Questionnaire (PHQ) to assess symptoms of
      depression and a Demographic Questionnaire. During the first 2 inpatient days, vital signs
      and CIWA scores will be obtained (by FRH personnel) every 4 hours or whenever subjects report
      or nurses observe the onset of withdrawal symptoms. On the 3rd inpatient day, these measures
      will be obtained 3 times. And on subsequent inpatient days, these measures will be obtained
      once each day and whenever withdrawal symptoms increase. Subjects will complete the PACS and
      the SSTAI prior to administration of the 2nd test dose on each inpatient day starting the day
      after they enter the study. Blood will be drawn early on inpatient day 3 for electrolyte
      measurements.

      In all subjects participating in the inpatient phase of the study, lorazepam (2 mg), a
      standard medication to decrease withdrawal symptoms, will be administered by mouth (PO)
      whenever CIWA scores are ≥ 7. CIWA scores will be repeated 1 h after each lorazepam dose and
      another dose given if the CIWA score remains ≥ 7. Also, lorazepam (2 mg) will be administered
      if subjects are found to have any of the following elevated vital signs (even if CIWA scores
      remain low): pulse > 110; diastolic blood pressure > 100; systolic blood pressure > 160.
      Vital signs (as well as CIWA) will be repeated 1 h after each lorazepam dose and another dose
      will be given if any of the elevated measures persist. If a subject's CIWA score remains ≥ 7,
      pulse remains > 110 or diastolic blood pressure remains > 100 after 8 consecutive lorazepam
      doses, systolic blood pressure remains > 160 after 3 lorazepam doses, or CIWA scores steadily
      increase despite receiving 3 consecutive lorazepam doses or dangerous symptoms develop (e.g.,
      the onset of hallucinations), a more aggressive detoxification regimen will be initiated and
      the subject will be dropped from the study. All patients admitted to FRH for alcohol
      detoxification receive thiamine, folate and multivitamins supplementation.

      Initiating Outpatient Test Treatment: Subjects recruited into the outpatient phase of the
      study at the end of an inpatient admission for medical detoxification from alcohol will be
      randomized to a treatment group and begin intranasal test treatment during their first
      outpatient clinic visit after discharge from FRH or UNC Hospitals. Subjects recruited from
      the community will be randomized and begin intranasal test treatments at a outpatient clinic
      visit scheduled shortly after their screening clinic visit if assessments at the latter visit
      indicate they meet inclusion criteria and not exclusion criteria. Several measures will be
      obtained at the beginning of the clinic visit when subjects begin self-administration of test
      treatments: Breathalyzer reading, CIWA rating, TLFB interview assessment of recent alcohol
      consumption, self-ratings on the SSTAI and PACS. Research personnel will then instruct
      subjects in intranasal self-administration technique and then observe subjects take their
      first intranasal test dose. Subjects will be given written instructions on intranasal
      self-administration technique, cleaning the spray bottle nozzle after each dose, storing
      spray bottles between doses and contacting study personnel if they have question, difficulty
      with the self-administration procedure or may be experiencing side effects. At the end of the
      clinic visit, subjects will take home a 60 ml spray bottle (that ejects 0.1 ml metered dose
      per insufflation) containing 25 ml of test solution which they will use to self-administer
      test treatment doses twice daily (6 insufflations/dose).

      Outpatient clinic visits during the treatment period: Subjects will have follow-up outpatient
      clinic visits at weeks 1, 2, 3, 4, 6, 8, 10 and 12 after starting intranasal test treatments.
      Outpatient visits will take place in the Psychiatry Clinics in the UNC Neurosciences Hospital
      or the Alcohol and Substance Abuse Program (ASAP) clinic which is located off of the UNC
      campus on a bus line making it more convenient for participants to commute and park thereby
      facilitating their compliance with the outpatient portion of the study. To enhance
      continuity, the first visit will be 2-3 days after the clinic visit during which intranasal
      test treatments are started. At each clinic visit, a Breathalyzer reading, a CIWA score and
      vital signs will be obtained, a TLFB interview administered to quantify daily alcohol intake
      since the last clinic visit, and the SSTAI, PACS and PHQ questionnaires will be completed.
      Subjects will be given a fresh 60 ml intranasal spray bottle containing 25 ml of test
      substance at clinic visits every 2 weeks. At each clinic visit, subjects' spray bottles will
      be weighed to monitor compliance. Their intranasal self-administration technique will be
      reviewed and, if necessary, subjects will be reinstructed in proper technique. At 4, 8 and 12
      weeks, blood will be drawn for CBC, liver functions, electrolytes, BUN, creatinine, and a
      urine sample will be obtained for drug screening and pregnancy tests on all female subjects.

      During each clinic visit, 15 minutes of substance use counseling (Medical Management) will be
      provided.
    

Intervention name(s): intranasal oxytocin spray; Intranasal Placebo Spray
Intervention type(s): Drug; Drug
Intervention description(s): Administration of oxytocin in a nasal spray; Intranasal Placebo Spray
Other intervention name(s): Syntocinon Spray; Placebo
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: oxytocin; alcohol withdrawal; alcohol dependence; alcoholism