Back to resultsOxytocin or Galantamine Versus Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia (CIDAR-3)
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Oxytocin
Galantamine
Placebo-Oxytocin
Placebo-Galantamine
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, oxytocin, galantamine
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.
Sites / Locations
- Baltimore VA Medical Center
- Community Mental Health Centers
- Keypoint Community Mental Health Centers
- Maryland Psychiatric Research Center
- Maryland Psychiatric Research Center
- Keypoint Mental health Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
1: galantamine/placebo-oxytocin
2: oxytocin/placebo-galantamine
3: placebo-galantamine /placebo-oxytocin
Arm Description
Subjects randomized to galantamine will receive galantamine and placebo-oxytocin
Subjects randomized to oxytocin will receive oxytocin and placebo-galantamine
Subjects randomized to placebo will receive placebo-galantamine and placebo-oxytocin
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
Vital Signs - Diastolic Blood Pressure
Mean diastolic blood pressure by treatment and follow-up week
Vital Signs - Systolic Blood Pressure
Mean systolic blood pressure by treatment and follow-up week
Vital Signs - Weight
Mean weight (kg) by treatment and follow-up week
Vital Signs - Pulse
Mean sitting pulse (bpm) by treatment and follow-up week
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.
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.
Electrocardiogram (EKG)
Mean corrected QT interval (QTc) by study week and treatment.
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.
Blood Oxytocin Levels
Blood Oxytocin Levels by Treatment and Visit
Laboratory Measures - ALT/SGPT
Alanine transaminase/serum glutamic-pyruvic transaminase (ALT/SGPT) blood levels by treatment group and visit.
Laboratory Measures - AST/SGOT
Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) blood levels by treatment group and visit.
Laboratory Measures - Alkaline Phosphatase
Alkaline phosphatase blood level by treatment group and visit.
Laboratory Measures - Calcium
Calcium blood levels by treatment group and visit.
Laboratory Measures - Sodium
Sodium blood levels by treatment group and visit.
Laboratory Measures - Potassium
Potassium blood levels by treatment group and visit.
Laboratory Measures - Chloride
Chloride blood levels by treatment group and visit.
Laboratory Measures - CO2
Carbon Dioxide (CO2) blood levels by treatment group and visit.
Laboratory Measures - Cholesterol
Total cholesterol blood levels by treatment group and visit.
Laboratory Measures - HDL
High-density lipoprotein (HDL) blood levels by treatment group and visit.
Laboratory Measures - LDL
Low-density lipoprotein (LDL) blood levels by treatment group and visit.
Laboratory Measures - Triglycerides
Triglyceride blood levels by treatment group and visit.
Laboratory Measures - VLDL
Very low density lipoprotein (VLDL) blood levels by treatment group and visit.
Laboratory Measures - Glucose
Glucose blood levels by treatment group and visit.
Laboratory Measures - Albumin
Albumin blood levels by treatment group and visit.
Laboratory Measures - Globulin
Globulin blood levels by treatment group and visit.
Laboratory Measures - A/G Ratio
Albumin to Globulin (A/G) ratio in the blood by treatment group and visit.
Laboratory Measures - Bilirubin
Bilirubin blood level by treatment group and visit.
Laboratory Measures - Protein
Protein blood level by treatment group and visit.
Laboratory Measures - BUN
BUN blood level by treatment group and visit.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Neurocognitive Assessment Battery (MCCB) - Composite Score
MCCB Composite Score by Week ranging from -10-100 with a higher score indicating a better outcome.
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.
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01012167
First Posted
April 28, 2009
Last Updated
January 10, 2022
Sponsor
University of Maryland, Baltimore
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT01012167
Brief Title
Oxytocin or Galantamine Versus Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia
Acronym
CIDAR-3
Official Title
Oxytocin or Galantamine vs. Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The project is designed to address the following two primary aims:
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.
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:
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.
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:
To determine whether changes in markers of negative symptom liability are correlated with changes in SANS total score.
To determine whether changes in markers of cognitive impairment liability are correlated with changes in the composite neurocognitive score.
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.
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, oxytocin, galantamine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1: galantamine/placebo-oxytocin
Arm Type
Active Comparator
Arm Description
Subjects randomized to galantamine will receive galantamine and placebo-oxytocin
Arm Title
2: oxytocin/placebo-galantamine
Arm Type
Active Comparator
Arm Description
Subjects randomized to oxytocin will receive oxytocin and placebo-galantamine
Arm Title
3: placebo-galantamine /placebo-oxytocin
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to placebo will receive placebo-galantamine and placebo-oxytocin
Intervention Type
Drug
Intervention Name(s)
Oxytocin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Galantamine
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Placebo-Oxytocin
Intervention Description
Saline nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration
Intervention Type
Other
Intervention Name(s)
Placebo-Galantamine
Intervention Description
Placebo tablets twice a day for 6 weeks
Primary Outcome Measure Information:
Title
Scale for the Assessment of Negative Symptoms (SANS) Total Score
Description
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
Title
Mean Z-Scores for Composite Cognitive Primary Outcome* by Treatment Group and Week
Description
* 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
Secondary Outcome Measure Information:
Title
Scale for the Assessment of Negative Symptoms (SANS) - Avolition
Description
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
Title
Scale for the Assessment of Negative Symptoms (SANS) - Anhedonia
Description
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
Title
Scale for the Assessment of Negative Symptoms (SANS) - Alogia
Description
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
Title
Scale for the Assessment of Negative Symptoms (SANS) - Blunted Affect
Description
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
Title
Brief Psychiatric Rating Scale (BPRS) - Total Score
Description
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
Title
Brief Psychiatric Rating Scale (BPRS) - Psychosis Score
Description
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
Title
Calgary Depression Scale (CDS) - Total Score
Description
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
Title
Arizona Sexual Experience Questionnaire (ASEX) Female
Description
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
Title
Arizona Sexual Experience Questionnaire (ASEX) Male
Description
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
Title
Vital Signs - Diastolic Blood Pressure
Description
Mean diastolic blood pressure by treatment and follow-up week
Time Frame
Weekly for 6 weeks
Title
Vital Signs - Systolic Blood Pressure
Description
Mean systolic blood pressure by treatment and follow-up week
Time Frame
Weekly for 6 weeks
Title
Vital Signs - Weight
Description
Mean weight (kg) by treatment and follow-up week
Time Frame
Weekly for 6 weeks
Title
Vital Signs - Pulse
Description
Mean sitting pulse (bpm) by treatment and follow-up week
Time Frame
Weekly for 6 weeks
Title
Simpson-Angus Scale (SAS)
Description
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
Title
Abnormal Involuntary Movement Scale (AIMS)
Description
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
Title
Electrocardiogram (EKG)
Description
Mean corrected QT interval (QTc) by study week and treatment.
Time Frame
Once during Evaluation and once at Treatment Week 6
Title
Barnes Akathisia Scale (BAS) - Global Score
Description
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
Title
Blood Oxytocin Levels
Description
Blood Oxytocin Levels by Treatment and Visit
Time Frame
Treatment Week 0 and Week 6
Title
Laboratory Measures - ALT/SGPT
Description
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
Title
Laboratory Measures - AST/SGOT
Description
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
Title
Laboratory Measures - Alkaline Phosphatase
Description
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
Title
Laboratory Measures - Calcium
Description
Calcium blood levels by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - Sodium
Description
Sodium blood levels by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - Potassium
Description
Potassium blood levels by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - Chloride
Description
Chloride blood levels by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - CO2
Description
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
Title
Laboratory Measures - Cholesterol
Description
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
Title
Laboratory Measures - HDL
Description
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
Title
Laboratory Measures - LDL
Description
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
Title
Laboratory Measures - Triglycerides
Description
Triglyceride blood levels by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - VLDL
Description
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
Title
Laboratory Measures - Glucose
Description
Glucose blood levels by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - Albumin
Description
Albumin blood levels by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - Globulin
Description
Globulin blood levels by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - A/G Ratio
Description
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
Title
Laboratory Measures - Bilirubin
Description
Bilirubin blood level by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - Protein
Description
Protein blood level by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Laboratory Measures - BUN
Description
BUN blood level by treatment group and visit.
Time Frame
Once during evaluation and once at the end of 6 weeks of study treatment
Title
Side Effect Checklist (SEC) - Abdominal Pain
Description
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
Title
Side Effect Checklist (SEC) - Anorexia
Description
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
Title
Side Effect Checklist (SEC) - Bruising Easily
Description
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
Title
Side Effect Checklist (SEC) - Constipation
Description
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
Title
Side Effect Checklist (SEC) - Diarrhea
Description
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
Title
Side Effect Checklist (SEC) - Dizziness
Description
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
Title
Side Effect Checklist (SEC) - Dry Eye
Description
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
Title
Side Effect Checklist (SEC) - Dry Mouth
Description
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
Title
Side Effect Checklist (SEC) - Enuresis
Description
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
Title
Side Effect Checklist (SEC) - Excessive Tearing of the Eye
Description
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
Title
Side Effect Checklist (SEC) - Fever
Description
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
Title
Side Effect Checklist (SEC) - Headache
Description
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
Title
Side Effect Checklist (SEC) - Hyperhydrosis
Description
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
Title
Side Effect Checklist (SEC) - Hypersalivation
Description
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
Title
Side Effect Checklist (SEC) - Insomnia
Description
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
Title
Side Effect Checklist (SEC) - Malaise
Description
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
Title
Side Effect Checklist (SEC) - Mucosal Ulceration
Description
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
Title
Side Effect Checklist (SEC) - Nasal Irritation
Description
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
Title
Side Effect Checklist (SEC) - Nausea
Description
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
Title
Side Effect Checklist (SEC) - Rash
Description
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
Title
Side Effect Checklist (SEC) - Restlessness
Description
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
Title
Side Effect Checklist (SEC) - Sedation
Description
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
Title
Side Effect Checklist (SEC) - Sore Throat
Description
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
Title
Side Effect Checklist (SEC) - Stiffness
Description
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
Title
Side Effect Checklist (SEC) - Tinnitus
Description
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
Title
Side Effect Checklist (SEC) - Tremor
Description
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
Title
Side Effect Checklist (SEC) - Urticaria
Description
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
Title
Side Effect Checklist (SEC) - Uterine Contractions
Description
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
Title
Side Effect Checklist (SEC) - Vomiting
Description
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
Title
Side Effect Checklist (SEC) - Weight Loss
Description
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
Title
Side Effect Checklist (SEC) - Wheezing
Description
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
Title
Neurocognitive Assessment Battery (MCCB) - Composite Score
Description
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).
Title
Neurocognitive Assessment Battery (MCCB) - Attention Vigilance
Description
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).
Title
Neurocognitive Assessment Battery (MCCB) - Processing Speed
Description
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).
Title
Neurocognitive Assessment Battery (MCCB) - Reasoning/Problem Solving
Description
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).
Title
Neurocognitive Assessment Battery (MCCB) - Social Cognition
Description
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).
Title
Neurocognitive Assessment Battery (MCCB) - Verbal Learning
Description
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).
Title
Neurocognitive Assessment Battery (MCCB) - Visual Learning
Description
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).
Title
Neurocognitive Assessment Battery (MCCB) - Working Memory
Description
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).
Title
Positive and Negative Affect Schedule (PANAS) - Negative
Description
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
Title
Positive and Negative Affect Schedule (PANAS) - Positive
Description
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
Title
Reactions to Partner
Description
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
Title
Willingness to Interact
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William T Carpenter, M.D.
Organizational Affiliation
Maryland Psychiatric Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Baltimore VA Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Community Mental Health Centers
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Keypoint Community Mental Health Centers
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21222
Country
United States
Facility Name
Maryland Psychiatric Research Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21228
Country
United States
Facility Name
Maryland Psychiatric Research Center
City
Catonsville
State/Province
Maryland
ZIP/Postal Code
21228
Country
United States
Facility Name
Keypoint Mental health Center
City
Dundalk
State/Province
Maryland
ZIP/Postal Code
21222
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Oxytocin or Galantamine Versus Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia
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