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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
86
Oxytocin: 24 IU in the morning and 24 IU in the evening given by nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration
Galantamine: 4 mg twice a day for 1 week, then 8 mg twice a day for 1 week, then 12 mg twice a day for 4 weeks
Saline nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration
Placebo tablets twice a day for 6 weeks
Baltimore VA Medical Center
Baltimore, Maryland, United States
Community Mental Health Centers
Baltimore, Maryland, United States
Keypoint Community Mental Health Centers
Baltimore, Maryland, United States
Maryland Psychiatric Research Center
Baltimore, Maryland, United States
Maryland Psychiatric Research Center
Catonsville, Maryland, United States
Keypoint Mental health Center
Dundalk, Maryland, United States
Scale for the Assessment of Negative Symptoms (SANS) Total Score
Mean SANS Total Score by Treatment and Week. SANS total score range = 0-85. Higher scores indicate more severe negative symptoms.
Time frame: Every other week for 6 weeks
Mean Z-Scores for Composite Cognitive Primary Outcome* by Treatment Group and Week
\* Composite Cognitive Primary Outcome = mean of z-scores from the Brief Assessment of Cognition in Schizophrenia (BACS) Symbol Digit test, the Hopkins Verbal Learning Test (HVLT), and the Rapid Visual Information Processing test (RVIP). Z-scores for each test were calculated as Z = (individual patient score - pooled baseline mean)/(pooled baseline standard deviation). Higher values of the composite score represent a better outcome.
Time frame: Treatment Week 0 and Week 6
Scale for the Assessment of Negative Symptoms (SANS) - Avolition
Mean score by treatment and week. Scores range from 0-5, with higher scores indicating a worse outcome.
Time frame: Every other week for 6 weeks
Scale for the Assessment of Negative Symptoms (SANS) - Anhedonia
Mean score by treatment and week. Scores range from 0-5, with higher scores indicating a worse outcome.
Time frame: Every other week for 6 weeks
Scale for the Assessment of Negative Symptoms (SANS) - Alogia
Mean score by treatment and week. Scores range from 0-5, with higher scores indicating a worse outcome.
Time frame: Every other week for 6 weeks
Scale for the Assessment of Negative Symptoms (SANS) - Blunted Affect
Mean score by treatment and week. Scores range from 0-5, with higher scores indicating a worse outcome.
Time frame: Every other week for 6 weeks
Brief Psychiatric Rating Scale (BPRS) - Total Score
The total BPRS score is calculated by adding the scores for scales #1-#18. Each scale ranges from "1=Not Present" to "7=Very Severe". Total scores range from a minimum score of 18 to a maximum score of 126. A higher total score indicates a more severe psychiatric symptom rating.
Time frame: Every other week for 6 weeks
Brief Psychiatric Rating Scale (BPRS) - Psychosis Score
The psychosis score is calculated by adding the scores for scales #4 Conceptual Disorganization, #11 Suspiciousness, #12 Hallucinatory Behavior, and #15 Unusual Thought Content. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum psychosis score is 4 and the maximum psychosis score is 28. A higher score indicates a more severe psychosis rating.
Time frame: Every other week for 6 weeks
Calgary Depression Scale (CDS) - Total Score
Total score calculated by adding scores for scales #1-#9. Each scale ranges from "0=Absent" to "3=Severe". The minimum total CDS score is 0 and the maximum total CDS score is 27. A higher score indicates a more severe depression rating.
Time frame: Every other week for 6 weeks
Arizona Sexual Experience Questionnaire (ASEX) Female
Mean ASEX total scores by treatment and week for female participants. Total scores are calculated by adding scores for scales #1-#5. Each scale ranges from "1=Easily/Extremely" to "6=Never/None". The minimum total ASEX score is 5 and the maximum score is 30. Lower scores indicate more positive sexual experiences.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Arizona Sexual Experience Questionnaire (ASEX) Male
Mean ASEX total scores by treatment and week for male participants. Total scores are calculated by adding scores for scales #1-#5. Total scores are calculated by adding scores for scales #1-#5. Each scale ranges from "1=Easily/Extremely" to "6=Never/None". The minimum total ASEX score is 5 and the maximum score is 30. Lower scores indicate more positive sexual experiences.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Vital Signs - Diastolic Blood Pressure
Mean diastolic blood pressure by treatment and follow-up week
Time frame: Weekly for 6 weeks
Vital Signs - Systolic Blood Pressure
Mean systolic blood pressure by treatment and follow-up week
Time frame: Weekly for 6 weeks
Vital Signs - Weight
Mean weight (kg) by treatment and follow-up week
Time frame: Weekly for 6 weeks
Vital Signs - Pulse
Mean sitting pulse (bpm) by treatment and follow-up week
Time frame: Weekly for 6 weeks
Simpson-Angus Scale (SAS)
SAS total score for extrapyramidal side effects: Frequencies of greatest within-participant increase (worsening) from pre-treatment baseline, by treatment group. Total scores calculated by adding scores from scales #1-#11. Each scale ranges from "0=None/Normal" to "4=Extreme/Severe". The minimum total score is 0 and the maximum score is 44. Higher scores indicate a more severe extrapyramidal side effect rating.
Time frame: Baseline, week 3, and week 6
Abnormal Involuntary Movement Scale (AIMS)
AIMS Total Score: Frequencies of Maximum Within- Participant Increases (worsening) from Baseline by Treatment Group. Total score calculated by adding scores from scales #1-#10. Each scale ranges from "0=None" to "4=Severe". The minimum total AIMS score is 0 and the maximum score is 40. Higher scores indicate a more severe abnormal involuntary movement rating.
Time frame: Treatment Week 0 and Week 6
Electrocardiogram (EKG)
Mean corrected QT interval (QTc) by study week and treatment.
Time frame: Once during Evaluation and once at Treatment Week 6
Barnes Akathisia Scale (BAS) - Global Score
For each subject, the largest increase from baseline in the global akathisia score at any visit during follow-up was calculated. The global akathisia score ranges from "0=Absent" to "5=Severe Akathisia". Higher scores indicate a more severe global rating of akathisia.
Time frame: Treatment Week 0 and Week 6
Blood Oxytocin Levels
Blood Oxytocin Levels by Treatment and Visit
Time frame: Treatment Week 0 and Week 6
Laboratory Measures - ALT/SGPT
Alanine transaminase/serum glutamic-pyruvic transaminase (ALT/SGPT) blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - AST/SGOT
Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Alkaline Phosphatase
Alkaline phosphatase blood level by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Calcium
Calcium blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Sodium
Sodium blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Potassium
Potassium blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Chloride
Chloride blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - CO2
Carbon Dioxide (CO2) blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Cholesterol
Total cholesterol blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - HDL
High-density lipoprotein (HDL) blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - LDL
Low-density lipoprotein (LDL) blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Triglycerides
Triglyceride blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - VLDL
Very low density lipoprotein (VLDL) blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Glucose
Glucose blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Albumin
Albumin blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Globulin
Globulin blood levels by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - A/G Ratio
Albumin to Globulin (A/G) ratio in the blood by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Bilirubin
Bilirubin blood level by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Protein
Protein blood level by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - BUN
BUN blood level by treatment group and visit.
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Side Effect Checklist (SEC) - Abdominal Pain
Percentage of participants with new onset or worsening compared to baseline of "Abdominal Pain" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Anorexia
Percentage of participants with new onset or worsening compared to baseline of "Anorexia" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Bruising Easily
Percentage of participants with new onset or worsening compared to baseline of "Bruising Easily" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Constipation
Percentage of participants with new onset or worsening compared to baseline of "Constipation" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Diarrhea
Percentage of participants with new onset or worsening compared to baseline of "Diarrhea" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Dizziness
Percentage of participants with new onset or worsening compared to baseline of "Dizziness" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Dry Eye
Percentage of participants with new onset or worsening compared to baseline of "Dry Eye" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Dry Mouth
Percentage of participants with new onset or worsening compared to baseline of "Dry Mouth" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Enuresis
Percentage of participants with new onset or worsening compared to baseline of "Enuresis" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Excessive Tearing of the Eye
Percentage of participants with new onset or worsening compared to baseline of "Excessive Tearing of the Eye" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Fever
Percentage of participants with new onset or worsening compared to baseline of "Fever" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Headache
Percentage of participants with new onset or worsening compared to baseline of "Headache" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Hyperhydrosis
Percentage of participants with new onset or worsening compared to baseline of "Hyperhydrosis" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Hypersalivation
Percentage of participants with new onset or worsening compared to baseline of "Hypersalivation" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Insomnia
Percentage of participants with new onset or worsening compared to baseline of "Insomnia" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Malaise
Percentage of participants with new onset or worsening compared to baseline of "Malaise" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Mucosal Ulceration
Percentage of participants with new onset or worsening compared to baseline of "Mucosal Ulceration" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Nasal Irritation
Percentage of participants with new onset or worsening compared to baseline of "Nasal Irritation" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Nausea
Percentage of participants with new onset or worsening compared to baseline of "Nausea" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Rash
Percentage of participants with new onset or worsening compared to baseline of "Rash" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Restlessness
Percentage of participants with new onset or worsening compared to baseline of "Restlessness" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Sedation
Percentage of participants with new onset or worsening compared to baseline of "Sedation" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Sore Throat
Percentage of participants with new onset or worsening compared to baseline of "Sore Throat" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Stiffness
Percentage of participants with new onset or worsening compared to baseline of "Stiffness" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Tinnitus
Percentage of participants with new onset or worsening compared to baseline of "Tinnitus" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Tremor
Percentage of participants with new onset or worsening compared to baseline of "Tremor" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Urticaria
Percentage of participants with new onset or worsening compared to baseline of "Urticaria" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Uterine Contractions
Percentage of participants with new onset or worsening compared to baseline of "Uterine Contractions" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Vomiting
Percentage of participants with new onset or worsening compared to baseline of "Vomiting" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Weight Loss
Percentage of participants with new onset or worsening compared to baseline of "Weight Loss" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Wheezing
Percentage of participants with new onset or worsening compared to baseline of "Wheezing" rating on the SEC, by Treatment Group.
Time frame: Weekly for 6 weeks
Neurocognitive Assessment Battery (MCCB) - Composite Score
MCCB Composite Score by Week ranging from -10-100 with a higher score indicating a better outcome.
Time frame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
Neurocognitive Assessment Battery (MCCB) - Attention Vigilance
MCCB Attention Vigilance domain score by week calculated from the Continuous Performance Test, Identical Pairs version. The domain score scale is 20-80, with higher scores indicating a better outcome. .
Time frame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
Neurocognitive Assessment Battery (MCCB) - Processing Speed
MCCB Processing Speed domain score by week calculated from the Trail Making Test- Part A, Brief Assessment of Cognition in Schizophrenia- symbol coding subtest, and the Category fluency test- animal naming. The domain score scale is 20-80, with higher scores indicating a better outcome.
Time frame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
Neurocognitive Assessment Battery (MCCB) - Reasoning/Problem Solving
MCCB Reasoning/Problem Solving domain score by week calculated from the Neuropsychological Assessment Battery- mazes subtest. The domain score scale is 20-80, with higher scores indicating a better outcome.
Time frame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
Neurocognitive Assessment Battery (MCCB) - Social Cognition
MCCB Social Cognition domain score by week calculated from the Mayer-Salovey-Caruso Emotional Intelligence Test- managing emotions branch. The domain score scale is 20-80, with higher scores indicating a better outcome.
Time frame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
Neurocognitive Assessment Battery (MCCB) - Verbal Learning
MCCB Verbal Learning domain score by week calculated from the Hopkins Verbal Learning Test-Revised, immediate recall (three learning trials only). The domain score scale is 20-80, with higher scores indicating a better outcome.
Time frame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
Neurocognitive Assessment Battery (MCCB) - Visual Learning
MCCB Visual Learning domain score by week calculated from the Brief Visuospatial Memory Test-Revised. The domain score scale is 20-80, with higher scores indicating a better outcome.
Time frame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
Neurocognitive Assessment Battery (MCCB) - Working Memory
MCCB Working Memory domain score by week calculated from the Wechsler Memory Scale, 3rd ed., spatial span subtest. The domain score scale is 20-80, with higher scores indicating a better outcome.
Time frame: Once at Treatment Week 0 (baseline) and again at Treatment Week 6 (end of treatment).
Positive and Negative Affect Schedule (PANAS) - Negative
Participant reported responses after Brief Role Play rating how they felt during the role plays. Participants rated 12 negative affect items on a scale of 1-5, with 1 being "very slightly or not at all" and 5 being "extremely". The minimum score for this measure is 12 and the maximum score is 60. Higher scores indicate a higher rate of negative affect during the role plays.
Time frame: Treatment Week 0 and Week 6
Positive and Negative Affect Schedule (PANAS) - Positive
Participant reported responses after Brief Role Play rating how they felt during the role plays. Participants rated 12 positive affect items on a scale of 1-5, with 1 being "very slightly or not at all" and 5 being "extremely". The minimum score for this measure is 12 and the maximum score is 60. Higher scores indicate a higher rate of positive affect during the role plays.
Time frame: Treatment Week 0 and Week 6
Reactions to Partner
Participant reported responses after Brief Role Play. The Reactions to Partner item was calculated by totaling responses to 7 scales. Each scale score ranges from 1-5, which 1 being "completely agree" and 5 being "completely disagree". The minimum score for this measure is 7 and the maximum score is 35. Higher responses indicate a more negative reaction to their role play partner.
Time frame: Treatment Week 0 and Week 6
Willingness to Interact
Participant reported responses after Brief Role Play. The Willingness to Interact item calculated by totaling scores from items 1-6. Each score ranges from 1-5, with 1 being "definitely willing" and 5 being "definitely unwilling". The minimum score for this measure is 6 and the maximum score is 30. Lower scores indicate more willingness to interact with their role play partner again in the future.
Time frame: Treatment Week 0 and Week 6
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.