Oxytocin Treatment of Opioid Dependence
Condition: Opioid Dependence; Opioid Withdrawal
MeSH terms: Opioid-Related Disorders
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Purpose: The purpose of this research study is to learn whether oxytocin treatment decreases
      use of and cravings for opioids (narcotics) in people who have been using opioids heavily for
      long periods of time and are unable to stop on their own.

      Participants: Patients meeting DSM-IV-TR criteria for opioid dependence.

      Procedures (methods): Subjects will have standard medications available for withdrawal
      symptoms from opioids and standard psychosocial interventions available in the inpatient
      setting. In addition, subjects will self-administer intranasal test treatments 3 times daily.
    

Detailed description: 
      The purpose of this research study is to learn whether oxytocin treatment decreases use of
      and cravings for opioids (narcotics) in people who have been using opioids heavily for long
      periods and are unable to stop 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 for opioid dependence.

      People who use large amounts of opioids every day or many days per week for weeks or months
      undergo chemical changes in their brains. They continue to use opioids frequently and heavily
      because, even though they may know opioid use is not good for their health, they have
      unpleasant experiences if they stop or decrease the amount used. Those experiences can
      include increased anxiety, difficulty sleeping, difficulty tolerating stress, and a craving
      to use opioids, as well as physical symptoms of withdrawal such as feeling sweaty or having
      chills, bone or joint aches, muscle cramps, nausea, diarrhea. Studies have shown that giving
      oxytocin to opioid-addicted animals diminished opioid use after they had been denied access
      to opioids for a while and reduced symptoms when they were put into opioid withdrawal.

      This is a randomized, double-blind, Placebo-controlled trial in subjects with opioid
      dependence that will test the efficacy of intranasal Oxytocin (OT) treatment vs. Placebo
      (containing the same ingredients as the OT spray except OT) on:

        1. reducing opioid withdrawal symptoms and

        2. the total amount of standard, as needed (PRN) medications required to control withdrawal
           symptoms during medical opioid detoxification.

      Treatment assignments will be random within each sex. Each treatment group will be composed
      of up to 25 subjects. Essentially, this study involves adding daily OT or Placebo
      administration on a fixed schedule onto standard symptom triggered treatment of opioid
      withdrawal using non-opioid medications.

      Subjects will be recruited from patients admitted to the Addictions Detoxification Unit (ADU)
      at Wakebrook, the local mental health center for Wake County, NC for medical detoxification
      from opioids. There will be no selection on the basis of gender, ethnicity or race. ADU
      professional staff will be educated about inclusion and exclusion criteria for this study.
      They will describe the study to newly-admitted opioid-dependent patients who appear to meet
      criteria. If patients express interest in participation, ADU staff will either call the Study
      Coordinator (at UNC Hospitals) as soon as possible or inform a member of the research team
      who will visit the ADU each weekday morning. Also, research personnel will contact the ADU
      each morning and afternoon to inquire about newly admitted patients. If the Study Coordinator
      is contacted about a potential study candidate, the Coordinator will contact and inform the
      member of the research team who will visit ADU that morning about the potential study
      participant. As soon as possible after potential subjects are admitted to the ADU, research
      personnel will obtain informed consent and conduct an initial brief assessment to determine
      if subjects meet criteria for inclusion in the study.

      The brief assessment includes completion of:

        1. urine sample collection for rapid drug screen to confirm opioid use and to determine
           other current substance use and, in women, to test for pregnancy;

        2. a review of medical exclusion criteria;

        3. vital sign (VS) measurements;

        4. the M.I.N.I. psychiatric interview screening questions for psychotic disorders, severe
           major depression, mania, and suicidality;

        5. the Time Line Follow Back interview to quantify addictive substance consumption during
           the preceding 3 months;

        6. the Structured Clinical Interview for DSM-IV (SCID) Substance Use Disorders Module to
           determine if prospective subjects meet DSM-IV-R criteria for opioid dependence,
           currently meet criteria for opioid withdrawal, and currently or in the past 3 months
           have met criteria for dependence on substances that are exclusionary for this study;

        7. draw a 5-mL blood sample for serum sodium concentration assay. Physical examinations are
           completed by Wakebrook physicians within 24 hours after patients are admitted. Findings
           on physical examinations will not be available until later the day of admission or the
           following day, which will be after initiation of intranasal doses. If significant
           physical exam abnormalities are identified, treatments and further subject participation
           in the study will be stopped immediately. Vital signs are measured at regular intervals
           on these patients as part of clinical care. The investigators will draw blood to assay
           serum sodium concentrations as a safety measure for this study.

      If need be, prospective subjects will receive PRN medications for withdrawal symptoms before
      recruitment procedures are initiated or intranasal test treatments are begun. Treatment
      Protocol and Measures: If subjects qualify for inclusion in the study, their withdrawal
      symptoms will be immediately measured using the well-validated Clinical Opiate Withdrawal
      Scale (COWS) and they will complete self-rating of opioid craving using a 100-mm visual
      analog scale (VAS), Subjective Opioid Withdrawal Scale (SOWS) and a baseline Spielberger
      State-Trait Anxiety Inventory (SSTAI). This will be followed by self-administration of their
      first intranasal dose of the substance to which they have been randomized under supervision
      of research personnel or ADU professional staff. The second dose on the first day of
      admission will be given 2 hours after the first. A third dose will be given later on the
      first day of admission (at least 4 hours after the second dose). On subsequent days of
      admission, doses will be taken twice daily (shortly before breakfast or lunch and dinner).
      All inpatient self-administration of intranasal test doses will be monitored by ADU or
      research staff. Each dose will consist of 10 insufflations of Syntocinon Spray or placebo
      (containing the same ingredients as Syntocinon Spray except for Oxytocin). Each insufflation
      given 30 sec apart and alternating between nostrils. Oxytocin and Placebo doses are
      administered from identical blind-labeled 60-ml spray bottles that deliver 0.1 ml of
      aerosolized solution/spray per insufflation. Intranasal test treatments will be administered
      for up to 5 days. After the first intranasal test dose, research personnel will complete the
      rest of the M.I.N.I. psychiatric interview. During the first 2 inpatient days objective COWS
      and subjective SOWS subject self-rating of opioid craving will be obtained every 4 hours or
      whenever subjects report or nurses observe the onset of withdrawal symptoms. Subsequently,
      the COWS and SOWS measures will be obtained twice daily or whenever withdrawal symptoms
      increase for at least 2 additional days and longer if subjects continue to exhibit
      significant symptoms. Subjects will complete the VAS subjective rating of opioid craving and
      the State portion of the SSTAI on each inpatient day starting on admission day 2
      approximately 1 hour before their second intranasal test dose. In all subjects, per protocol,
      multiple as-needed non-opioid medications will be available for symptoms of opioid
      withdrawal.
    

Intervention name(s): Intranasal Oxytocin Spray; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 10 insufflations (40IU of oxytocin total) given three times on day of enrollment and then twice daily for 4 days; 10 insufflations (40IU of placebo, same solution as active treatment minus oxytocin) given three times on day of enrollment and then twice daily for 4 day
Other intervention name(s): Syntocinon spray
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Opioid Dependence; Opioid Withdrawal; Opioid; Oxytocin; OT (oxytocin); Intranasal administration