Clinical trial NCT01012167: Oxytocin or Galantamine Versus Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia
Official title: Oxytocin or Galantamine vs. Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Schizophrenia, oxytocin, galantamine
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2009-11-11
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The project is designed to address the following two primary aims:

1. To determine whether adjunctive oxytocin is superior to placebo for the treatment of persistent negative symptoms, as measured by the SANS total score, in people with schizophrenia.
2. To determine whether adjunctive Galantamine is superior to placebo for the treatment of cognitive impairments, as measured by improvement on a composite neurocognitive score in people with schizophrenia.

The investigators will also address the following secondary aims:

1. To determine whether people with schizophrenia treated with adjunctive oxytocin, compared to placebo, will show greater improvement on markers of negative symptom liability including: social affiliation, facial affect recognition, olfactory discrimination, initiation of smooth pursuit and latency of internally-driven saccades.
2. To determine whether people with schizophrenia treated with adjunctive Galantamine, compared to placebo, will show greater improvement on markers of cognitive impairment liability including: predictive pursuit, P50 sensory gating and visual-spatial working memory.

The investigators will address the following exploratory aims:

1. To determine whether changes in markers of negative symptom liability are correlated with changes in SANS total score.
2. To determine whether changes in markers of cognitive impairment liability are correlated with changes in the composite neurocognitive score.
3. To determine the response to oxytocin of all cognition domains assessed by the MATRICS battery, and to determine the response to Galantamine of all cognition domains assessed by the MATRICS, which are not included in the primary neurocognitive outcome score.
4. To determine whether there is a differential response of oxytocin and Galantamine on the SANS total score, composite neurocognitive score, and with the phenotypic measures of negative symptom and cognitive impairment liability.
5. To determine whether oxytocin and Galantamine are associated with:

   * adverse effects on positive or depressive symptoms;
   * adverse effects on motor symptoms;
   * adverse effects on laboratory and EKG measures;
   * increased occurrence of side effects;
   * social interest that is independent of sexual desire.


Eligibility criteria: Inclusion Criteria:

* Any race
* Subjects will meet DSM-IV criteria for schizophrenia or schizoaffective disorder
* Judged clinically stable and will not exceed threshold levels of positive, depressive, and/or extrapyramidal symptoms
* The minimum level of negative symptoms will be defined as follows:

  * Scale for the Assessment of Negative Symptoms (SANS) total score (minus the global items, and inappropriate affect, poverty of content of speech and attentional items) 20 or greater; OR
  * SANS alogia global item score 3 or greater
* The maximum level of psychotic, depressive, and extrapyramidal symptoms at the beginning and end of leading in:

  * Brief Psychiatric Rating Scale (BPRS) psychotic factor score (4-items) less or equal to 16
  * BPRS Anxiety/Depression factor score (4-items) less than or equal to 14
  * Simpson-Angus-Scale (SAS) total score (13-items) less than or equal to 10
* Subjects will be required to be on the same antipsychotic(s) for two months and on the same dose for the last month

Exclusion Criteria:

* Participants with an organic brain disorder; mental retardation; or a medical condition, whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
* Participants with intermittent alcohol or substance use will not be excluded unless they have met DSM-IV criteria for alcohol or substance abuse (other than nicotine) within the last month.
* Participants may be treated with one or more antipsychotics, except chlorpromazine, thioridazine, or mesoridazine. These latter antipsychotics are excluded because of the concern that their anticholinergic properties may interfere with the accurate assessment of galantamine efficacy.
* Participants may not be treated with anticholinergic medications or have clinically significant extrapyramidal symptoms. Additionally, subjects treated with glycopyrrolate will be accepted.
* Female participants may not be pregnant
* Female subjects may not be taking olanzapine at doses higher than 30 mg . Male subjects may not be taking olanzapine at doses higher than 40 mg.

Primary outcomes:
measure: Scale for the Assessment of Negative Symptoms (SANS) Total Score
timeFrame: Every other week for 6 weeks
measure: Mean Z-Scores for Composite Cognitive Primary Outcome* by Treatment Group and Week
timeFrame: Treatment Week 0 and Week 6
Secondary outcomes:
measure: Scale for the Assessment of Negative Symptoms (SANS) - Avolition
timeFrame: Every other week for 6 weeks
measure: Scale for the Assessment of Negative Symptoms (SANS) - Anhedonia
timeFrame: Every other week for 6 weeks
measure: Scale for the Assessment of Negative Symptoms (SANS) - Alogia
timeFrame: Every other week for 6 weeks
measure: Scale for the Assessment of Negative Symptoms (SANS) - Blunted Affect
timeFrame: Every other week for 6 weeks
measure: Brief Psychiatric Rating Scale (BPRS) - Total Score
timeFrame: Every other week for 6 weeks
measure: Brief Psychiatric Rating Scale (BPRS) - Psychosis Score
timeFrame: Every other week for 6 weeks
measure: Calgary Depression Scale (CDS) - Total Score
timeFrame: Every other week for 6 weeks
measure: Arizona Sexual Experience Questionnaire (ASEX) Female
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Arizona Sexual Experience Questionnaire (ASEX) Male
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Vital Signs - Diastolic Blood Pressure
timeFrame: Weekly for 6 weeks
measure: Vital Signs - Systolic Blood Pressure
timeFrame: Weekly for 6 weeks
measure: Vital Signs - Weight
timeFrame: Weekly for 6 weeks
measure: Vital Signs - Pulse
timeFrame: Weekly for 6 weeks
measure: Simpson-Angus Scale (SAS)
timeFrame: Baseline, week 3, and week 6
measure: Abnormal Involuntary Movement Scale (AIMS)
timeFrame: Treatment Week 0 and Week 6
measure: Electrocardiogram (EKG)
timeFrame: Once during Evaluation and once at Treatment Week 6
measure: Barnes Akathisia Scale (BAS) - Global Score
timeFrame: Treatment Week 0 and Week 6
measure: Blood Oxytocin Levels
timeFrame: Treatment Week 0 and Week 6
measure: Laboratory Measures - ALT/SGPT
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - AST/SGOT
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Alkaline Phosphatase
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Calcium
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Sodium
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Potassium
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Chloride
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - CO2
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Cholesterol
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - HDL
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - LDL
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Triglycerides
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - VLDL
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Glucose
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Albumin
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Globulin
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - A/G Ratio
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Bilirubin
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - Protein
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Laboratory Measures - BUN
timeFrame: Once during evaluation and once at the end of 6 weeks of study treatment
measure: Side Effect Checklist (SEC) - Abdominal Pain
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Anorexia
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Bruising Easily
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Constipation
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Diarrhea
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Dizziness
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Dry Eye
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Dry Mouth
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Enuresis
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Excessive Tearing of the Eye
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Fever
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Headache
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Hyperhydrosis
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Hypersalivation
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Insomnia
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Malaise
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Mucosal Ulceration
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Nasal Irritation
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Nausea
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Rash
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Restlessness
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Sedation
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Sore Throat
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Stiffness
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Tinnitus
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Tremor
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Urticaria
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Uterine Contractions
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Vomiting
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Weight Loss
timeFrame: Weekly for 6 weeks
measure: Side Effect Checklist (SEC) - Wheezing
timeFrame: Weekly for 6 weeks
measure: Neurocognitive Assessment Battery (MCCB) - Composite Score
timeFrame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
measure: Neurocognitive Assessment Battery (MCCB) - Attention Vigilance
timeFrame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
measure: Neurocognitive Assessment Battery (MCCB) - Processing Speed
timeFrame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
measure: Neurocognitive Assessment Battery (MCCB) - Reasoning/Problem Solving
timeFrame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
measure: Neurocognitive Assessment Battery (MCCB) - Social Cognition
timeFrame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
measure: Neurocognitive Assessment Battery (MCCB) - Verbal Learning
timeFrame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
measure: Neurocognitive Assessment Battery (MCCB) - Visual Learning
timeFrame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
measure: Neurocognitive Assessment Battery (MCCB) - Working Memory
timeFrame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
measure: Positive and Negative Affect Schedule (PANAS) - Negative
timeFrame: Treatment Week 0 and Week 6
measure: Positive and Negative Affect Schedule (PANAS) - Positive
timeFrame: Treatment Week 0 and Week 6
measure: Reactions to Partner
timeFrame: Treatment Week 0 and Week 6
measure: Willingness to Interact
timeFrame: Treatment Week 0 and Week 6
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Baltimore VA Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Community Mental Health Centers
state: Maryland
city: Baltimore
country: United States
facility: Keypoint Community Mental Health Centers
state: Maryland
city: Baltimore
country: United States
facility: Maryland Psychiatric Research Center
state: Maryland
city: Catonsville
country: United States
facility: Maryland Psychiatric Research Center
state: Maryland
city: Dundalk
country: United States
facility: Keypoint Mental health Center
state: Maryland
Study officials:
affiliation: Maryland Psychiatric Research Center
name: William T Carpenter, M.D.
role: PRINCIPAL_INVESTIGATOR
References: