Oxytocin Treatment of Schizophrenia
Condition: Paranoia; Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders; Paranoid Disorders
Study type: Interventional

Summary: 
      Purpose: Test whether intranasal administration of the neuropeptide, oxytocin, improves
      social cognition, social functioning and decreases paranoia and other psychotic symptoms in
      schizophrenia.

      Participants: Up to 80 adults with schizophrenia for at least one year and with a high rating
      for paranoia.

      Procedures (methods): Oxytocin or placebo will be administered twice daily in an intranasal
      spray (6 insufflations/dose or 24 IU) for 6 weeks. Before, during and at the end of the
      trial, each subject will undergo social cognitive measures (primary outcomes) and psychiatric
      symptom ratings (secondary outcomes).
    

Detailed description: 
      Inclusion criteria: meeting Diagnostic and Statistical Manual IV (DSM-IV) criteria for
      paranoid or undifferentiated schizophrenia for at least 1 year; scoring > 4 on the
      suspiciousness/persecution (hereafter referred to as paranoia) subscale of the Positive and
      Negative Symptom Scale (PANSS) or 3 on the paranoia subscale and > 3 on the hostility, active
      social avoidance, passive/apathetic social withdrawal or uncooperativeness subscale and > 60
      on the full PANSS: stability of symptom severity and on the same medication(s) and dose(s)
      for at least 1 month; low to moderate depressive symptoms.

      Exclusion criteria: low literacy as indicated by an inability to read and understand the
      consent form; dependence on substances other than tobacco or caffeine; positive urine drug
      screen for illegal substances or drugs that have not been prescribed; debilitating medical
      conditions (including AIDS; HIV infection alone will not be grounds for exclusion); major
      surgery or trauma in the past year will be grounds for exclusion although subjects determined
      to be recovered and stable may be included at the discretion of the Principal Investigator
      (PI); pregnancy, breast-feeding; having given birth in the past 6 months or breast-feeding in
      the past 3 months. Individuals judged unable to learn self-administration of intranasal
      treatments and/or not sufficiently reliable to do so will be excluded. Abnormalities found
      during medical evaluation will be grounds for exclusion (see details below) although subjects
      with laboratory measures somewhat out of the normal range may be included at the discretion
      of Drs. Pedersen, Gilmore, Rau and/or Salimi.

      Study Design: Randomized, double-blind, placebo-controlled design. Up to 80 subjects will
      complete the protocol: 40 will receive oxytocin; 40 placebo. Prior to the treatment trial,
      baseline measures will be obtained. Social cognition and psychiatric symptoms will be
      measured at Baseline and at 6 weeks of the 6 week treatment trial.

      Procedures: Subjects will be recruited from the University of North Carolina (UNC) Department
      of Psychiatry outpatient clinics and the community. If total Positive and Negative Symptoms
      Scale (PANSS) score is > or equal to 60, PANSS sub-score for suspiciousness/persecution is >
      or equal to 4, their medical history will be reviewed including medications and dosages over
      the past month. If they do not have exclusionary medical or medication history, their
      psychiatric history will be reviewed. If necessary to confirm their diagnosis, they will
      undergo the Structured Clinical Interview for DSM-IV (SCID) patient version. If they have met
      criteria for schizophrenia, paranoid or undifferentiated type, for at least one year, they
      will undergo a physical exam and blood will be drawn and urine collected for laboratory
      measures including complete blooc count (CBC), electrolytes, blood urea nitrogen (BUN),
      creatinine, liver function tests, glucose, thyroid-stimulating hormone (TSH), urinanalysis,
      urine drug screen and pregnancy test. This initial evaluation may require up to 3-4 hours.
      Prospective subjects will be encouraged to rest for 20-30 minutes between the initial
      interviews (PANSS, SCID) and the history, physical exam and blood/urine collections.
      Psychiatric, medical and medication history will be confirmed by reviewing medical records
      and contacting clinicians in charge of the prospective subject's psychiatric care. The
      initial evaluation will be conducted in the Clinical and Translational Research Center (CTRC)
      outpatient clinic or at the UNC Psychiatry Clinical Research Unit (CRU) at Central Regional
      Hospital (Raleigh or Butner).

      SCID, PANSS, other psychological results and medical labs and history will be reviewed during
      conferences with Dr. Pedersen accompanied by Drs. Gilmore, Salimi and/or Rau. Consensus
      decisions will be made during these conferences about whether subjects meet the diagnostic
      and other criteria for inclusion in the study.

      For subjects who meet study criteria, baseline measurements of social cognition, social
      competence, social functioning, paranoia, other psychotic and psychiatric symptoms will be
      obtained.

      During the treatment trial, twice daily test treatments will be self-administered by subjects
      in the morning shortly after breakfast and late in the afternoon/early evening prior to
      dinner. Each treatment will consist of 6 insufflations (3/nostril alternating between
      nostrils) of Syntocinon Spray (Novartis), which contains approximately 24 international units
      (IU) of oxytocin, or placebo. There will be a 30-60 second pause between each insufflation.
      The placebo solution will be a solution that has all ingredients in Syntocinon Spray except
      for oxytocin in 2 oz vials containing 30 ml of solution designed to deliver 0.1 ml metered
      volume per insufflation. Treatment assignments will be random within each gender.

      Social cognition and competence testing will begin 50 min after the morning treatment at 6
      weeks (day 42) of the treatment trial and will be followed by ratings of psychotic, mood and
      anxiety symptoms (requiring 1-3 hr depending on how much social cognition testing is done).
      The Emotion Recognition-40, Reading the Mind in the Eyes test (Eyes Test), Interpersonal
      Reactivity Index and Trustworthiness Tasks, Brune Theory of Mind Task, as well as psychiatric
      ratings will be conducted at all time points.

      Participants will be trained by research nurses during their first dosing with test substance
      in intranasal self-administration shortly after baseline measurements are completed. They
      will also be given written instructions about the timing of each day's test treatments and
      other procedures to follow at home. They will be given one 2 ounce vial containing 30 ml of
      test substance to last until their first outpatient clinic testing appointment and instructed
      when to begin the twice daily intranasal treatments. They will self administer test substance
      at the site so staff can confirm they are using proper technique. In addition to social
      cognition/competence testing and psychiatric ratings, blood samples as well as vital signs
      will be obtained during these visits. At 40 min after the last intranasal insufflation, blood
      (15 ml) will be drawn to measure plasma oxytocin concentrations and other lab values (sodium,
      potassium, glucose [treatment day 42], CBC, BUN, creatinine, liver function tests [treatment
      days 42]). An electrocardiogram (ECG) will also be obtained on the morning of treatment days
      42 approximately 3-4 hr after intranasal treatment (when social cognition/competence testing
      and psychiatric ratings are completed). Urine will also be collected from female subjects on
      the day of baseline measurements and on treatment day 42 for pregnancy testing. These same
      procedures will conducted on the morning of treatment day 42 in participants studied as
      inpatients.

      After procedures at the study site on the morning of treatment days 14 and 28, outpatient
      subjects will be given a new vial containing 30 ml test substance so they can self administer
      doses twice daily until their next visit to the study site. Subjects will be instructed to
      store vials at room temperature and to clean the tip of the spray nozzle with an alcohol wipe
      after each dose is administered. Vials will be weighted before dispensing and upon return to
      the clinic 2 wks later to determine how much solution was actually ejected from the vial.

      Measurements: A battery of well-validated instruments to quantify psychiatric symptoms,
      social cognition and social competence will be used in this study.
    

Intervention name(s): intranasal spray with oxytocin; nasal spray without oxytocin
Intervention type(s): Drug; Other
Intervention description(s): 6 insufflations (24 IU of oxytocin total) given twice daily for 6 weeks; 6 insufflations of nasal spray without oxytocin (0.1 metered dose/insufflation) twice daily for 6 weeks
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; social cognition; social skill; social functioning; paranoia; psychotic symptoms; schizophrenia; social deficits; intranasal administration