Oxytocin Treatment of Alcohol Withdrawal
Information source: University of North Carolina, Chapel Hill
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Alcohol Withdrawal
Intervention: intranasal oxytocin spray (Drug); intranasal spray without oxytocin (Other)
Phase: Phase 1
Sponsored by: University of North Carolina, Chapel Hill
Official(s) and/or principal investigator(s):
Cort A Pedersen, M.D., Principal Investigator, Affiliation: The University of North Carolina, Chapel Hill, Department of Psychiatry
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
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.
Official title: Oxytocin Treatment of Alcohol Withdrawal
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Total Lorazepam Dosage (in Milligrams)
Secondary outcome: CIWA-Ar Scores
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.
Minimum age: 18 Years.
Maximum age: 65 Years.
- Daily consumption of 6 or more alcohol drinks/day for at least 2 weeks prior to
- Only one of the following two conditions must be met:
1. At least one prior episode 2 days or longer in duration which the subject
experienced withdrawal symptoms that caused significant incapacitation.
2. At least one prior inpatient or outpatient medical detoxification during which
the subject exhibited withdrawal symptoms that sedative-hypnotic or
anticonvulsant medication was required at least once on 2 consecutive days after
cessation of or reduction in the use of alcohol following 2 weeks or more of
heavily daily consumption (6 or more drinks/day).
- Low literacy as indicated by an inability to read and understand the consent form.
- Dependence on substances other than alcohol, nicotine, caffeine or cannabis.
- History of alcohol withdrawal-related seizures, delirium tremens or hallucinations.
- Current or past alcohol-related medical complications (e. g. cirrhosis of the liver,
esophageal varices, severe gastritis, hemoptysis, hematochezia or melena).
- Current delirium, disorientation to place or persons, seizures, acute or unstable
psychosis or mania.
- Suicidal or homicidal ideation with strong intent, plans or recent attempt.
- Debilitating medical conditions (including AIDS, seizure disorder, emphysema, cancer
and not well-controlled diabetes/hypertension) [HIV infection, diabetes,
hypertension and asthma will not be grounds for exclusion]
- Diagnosis of amnesia, dementia, cognitive impairment or significant neurological
- Low body weight (BMI<17).
- History of anorexia nervosa or bulimia in the past 2 years.
- Significant trauma, self injurious behavior or surgery in the previous 2 months
- Pregnancy; giving birth or breast-feeding in the past 6 months.
- Ingestion during the 2 weeks prior to this admission of much more alcohol/day than
during previous drinking binges that preceded the onset of alcohol withdrawal
- Ingestion of more than 450 ml of alcohol/day.
- Chronic treatment with benzodiazepines, barbiturates, anticonvulsants or stimulants
- Treatment/ingestion in the 72 hours prior to enrollment in the study with long
half-life benzodiazepines or sedative hypnotic drugs.
- A blood alcohol level upon admission > 300 mg/dl.
- Well-documented history of inadequately treated baseline hypertension or tachycardia
(SBP>150 or DBP>100 or P>110).
Locations and Contacts
University of North Carolina Hospitals, Chapel Hill, North Carolina 27599, United States
Central Regional Hospital, Raleigh, North Carolina 27603, United States
UNC Department of Psychiatry
UNC Department of Psychiatry Research
Clinical Research Unit at Central Regional Hospital
Starting date: July 2010
Last updated: April 12, 2014