Oxytocin Treatment of Alcohol Withdrawal
Condition: Alcohol Withdrawal
Study type: Interventional
Phase: Phase 1

Summary: 
      Purpose: Test whether intranasal administration of the neuropeptide, oxytocin, is effective
      in decreasing alcohol withdrawal symptoms, the number of bouts of withdrawal requiring
      standard medication treatment (lorazepam) and the amount of lorazepam required to control
      withdrawal bouts in individuals undergoing medical detoxification. Also, determine rates of
      subject recruitment and retention in the inpatient setting.

      Participants: 80 alcohol dependent patients, 18-65 years of age, admitted for medical
      detoxification.

      Procedures (methods): Subjects will be inpatients undergoing medical detoxification from
      alcohol. Oxytocin or placebo will be administered in a nasal spray twice daily in a
      randomized, double blind manner for three days. Withdrawal symptoms will be measured
      routinely at q4 hours and prn for length of hospital stay. Lorazepam will be given whenever
      withdrawal symptoms increase above specific parameters.
    

Detailed description: 
      Study Design: This will be a double-blind, placebo controlled comparison of the efficacy of
      twice daily intranasal administration of oxytocin and placebo (saline) in reducing alcohol
      withdrawal symptoms, the number of bouts of withdrawal during which symptoms are of
      sufficient magnitude requiring prn lorazepam treatment (see definitions below) and the amount
      of lorazepam required to resolve withdrawal bouts. Treatment group assignment will be random
      within each sex. Subjects will be patients admitted to (University of North Carolina (UNC)
      Hospitals or the Dix Clinical Research Unit (CRU) for medical detoxification. Each treatment
      group will be composed of up to 40 subjects. Dr. Hamer, the study statistician, will
      construct a randomization plan to randomize 80 subjects to 2 groups of 40 subjects each with
      a blocksize of 4. This will be a permuted blocksize as this is a blind study.

      Procedures: Most patients who are admitted to the UNC Neuroscience Hospital Crisis
      Stabilization Unit, UNC Hospitals Family Practice or Hospitalist Services, or the Dix CRU for
      medical detoxification from alcohol will come in through the UNC Hospitals Emergency
      Department or Dorothea Dix Screening and Admissions during the late evening or early morning.
      Physical examination, medical and psychiatric history and lab tests (including complete blood
      count [CBC], magnesium, sodium, potassium, [blood urea nitrogen] BUN, creatinine, glucose,
      albumin, liver functions tests [ALT, AST, LDH, GGT], throid-stimulating hormone (TSH), B12,
      folate, urinalysis, urine toxicology screen and pregnancy test) are routinely obtained by the
      emergency department (ED)/ Dorothea Dix Screening and Admissions and/or inpatient unit during
      the admission process. Possibly in the UNC Hospitals ED/ Dorothea Dix Screening and
      Admissions and definitely after admission to these units, patients will have their vital
      signs (VSs) measured and their withdrawal symptoms quantified using the revised Clinical
      Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar scale, Sullivan et al 1989) on the
      schedule in the standard alcohol detoxification order set in the UNC Hospital electronic
      medical records system (CPOE) system. The CRU at Dorothea Dix will use a hard copy version of
      the CIWA used in the CPOE at UNC Hospitals.

      After consent is obtained, subjects will be randomly assigned to a treatment group (oxytocin
      or placebo). Prior to receiving their first intranasal treatment, an ECG will be obtained and
      blood drawn to obtain serum for assay of cytokine and allopregnanolone concentrations.
      Subjects also will rate their symptoms using the Alcohol Withdrawal Symptom Checklist (AWSC,
      Pittman et al 2007) prior to receiving their first test dose. These procedures will be
      done/overseen by research nurses or physicians. Subjects will usually receive their first
      intranasal test dose between 1000 and 1200 hours and will consist of 6 insufflations of
      Syntocinon Spray (approximately 24 IU) or placebo, with each insufflation given 30 seconds
      apart and alternating between nostrils. Test doses will be taken again at 1700 hr later that
      day (Admission Day 1) and at 0900 and 1700 hr on Admission Days 2 and 3. Oxytocin test
      treatments will be administered from 5 ml intranasal spray vials designed to deliver 0.1 ml
      metered volume per insufflation. The placebo treatments will be administered from 60 ml
      intranasal spray vials (each containing 30ml of solution) also designed to deliver 0.1ml
      metered volume per insufflation. Vials containing oxytocin and placebo spray will be blind
      labeled by the UNC Investigational Drug Service or the Dorothea Dix Hospital pharmacy.
      Research nurses or physicians will oversee subject self-administration of all intranasal test
      doses. After enrollment on admission day 1 and in the morning on admission days 2 and 3,
      subjects will be given multiple copies of the AWSC questionnaire and requested to complete
      one each time the unit nurses do CIWA ratings. These questionnaires will be retrieved by
      research staff the following morning. Shortly after the morning test dose on admission days 2
      and 3, subjects will complete the Alcohol Craving Visual Analog Scales (ACVAS), the Penn
      Alcohol Craving Scale, and the Profile of Mood States (McNair et al, 1971). On these same
      admission days, research nurses will also draw (and subsequently process) blood serum samples
      to assay cytokine and allopregnanolone concentrations shortly after the morning test dose.
      Additional blood will be drawn after the morning test dose on admission day 2 to obtain serum
      for tests to be run in McLendon Laboratories (magnesium, chloride, calcium, sodium,
      potassium, BUN, creatinine, and liver function tests). Another electrocardiogram (ECG) will
      also be obtained shortly after the morning test treatment on admission day 2. Research staff
      will retrieve on a daily basis CIWA ratings and vital sign measurements obtained on each
      subject from their electronic medical record.

      In all subjects, PRN lorazepam doses will be administered by mouth (PO) or intravenously (IV)
      (if subjects cannot take medication PO) whenever CIWA ratings are > 14 per the protocol in
      the standard alcohol detoxification order set in the UNC Hospital CPOE system. Lorazepam
      doses (1 - 4 mg) and frequency (q 2 -6 h) will be adjusted based on the severity of
      withdrawal symptoms. This same order set will be employed at the Dorothea Dix CRU.
    

Intervention name(s): intranasal oxytocin spray; intranasal spray without oxytocin
Intervention type(s): Drug; Other
Intervention description(s): 6 insufflations (24 IU of oxytocin total) given twice daily for 3 days; 6 insufflations (0.1 metered dose/insufflation) twice daily
Other intervention name(s): Syntocinon Spray
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: oxytocin; alcohol withdrawal; lorazepam; alcoholism; intranasal administration; CIWA-Ar