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Trial · Interventional

CompletedPhase 2Results postedRegistry data

Oxytocin or Galantamine Versus Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia

Short name CIDAR-3

NCTNCT01012167 (opens ClinicalTrials.gov in a new tab)Other idHP-00044324Other id1P50MH082999-01
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 2
Enrollment
86 participants (actual)
Sponsor
University of Maryland, Baltimore · Other
Design
Randomized · Quadruple masking
Countries
1 country

United States

Start
Feb 2010
Primary completion
Jul 2014
Completion
Jul 2014
First posted
11 Nov 2009 (estimated)
Last update posted
12 Jan 2022
Conditions
Schizophrenia

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201020112012201320142015
  1. Ph 2

    CIDAR-3

    NCT01012167

    Feb 2010 to Jul 2014

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • OxytocinDrug
  • GalantamineDrug
  • Placebo-OxytocinOther
  • Placebo-GalantamineOther

Arms3

  • Active comparator

    1: galantamine/placebo-oxytocin

    Subjects randomized to galantamine will receive galantamine and placebo-oxytocin

  • Active comparator

    2: oxytocin/placebo-galantamine

    Subjects randomized to oxytocin will receive oxytocin and placebo-galantamine

  • Placebo comparator

    3: placebo-galantamine /placebo-oxytocin

    Subjects randomized to placebo will receive placebo-galantamine and placebo-oxytocin

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Scale for the Assessment of Negative Symptoms (SANS) Total Score

    Time frame · Every other week for 6 weeks

    Registry description

    Mean SANS Total Score by Treatment and Week. SANS total score range = 0-85. Higher scores indicate more severe negative symptoms.

  2. Mean Z-Scores for Composite Cognitive Primary Outcome* by Treatment Group and Week

    Time frame · Treatment Week 0 and Week 6

    Registry 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.

Secondary outcomes(20)

  1. Scale for the Assessment of Negative Symptoms (SANS) - Avolition

    Time frame · Every other week for 6 weeks

    Registry description

    Mean score by treatment and week. Scores range from 0-5, with higher scores indicating a worse outcome.

  2. Scale for the Assessment of Negative Symptoms (SANS) - Anhedonia

    Time frame · Every other week for 6 weeks

    Registry description

    Mean score by treatment and week. Scores range from 0-5, with higher scores indicating a worse outcome.

  3. Scale for the Assessment of Negative Symptoms (SANS) - Alogia

    Time frame · Every other week for 6 weeks

    Registry description

    Mean score by treatment and week. Scores range from 0-5, with higher scores indicating a worse outcome.

  4. Scale for the Assessment of Negative Symptoms (SANS) - Blunted Affect

    Time frame · Every other week for 6 weeks

    Registry description

    Mean score by treatment and week. Scores range from 0-5, with higher scores indicating a worse outcome.

  5. Brief Psychiatric Rating Scale (BPRS) - Total Score

    Time frame · Every other week for 6 weeks

    Registry 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.

  6. Brief Psychiatric Rating Scale (BPRS) - Psychosis Score

    Time frame · Every other week for 6 weeks

    Registry 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.

  7. Calgary Depression Scale (CDS) - Total Score

    Time frame · Every other week for 6 weeks

    Registry 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.

  8. Arizona Sexual Experience Questionnaire (ASEX) Female

    Time frame · Once during evaluation and once at the end of 6 weeks of study treatment

    Registry 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.

  9. Arizona Sexual Experience Questionnaire (ASEX) Male

    Time frame · Once during evaluation and once at the end of 6 weeks of study treatment

    Registry 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.

  10. Vital Signs - Diastolic Blood Pressure

    Time frame · Weekly for 6 weeks

    Registry description

    Mean diastolic blood pressure by treatment and follow-up week

  11. Vital Signs - Systolic Blood Pressure

    Time frame · Weekly for 6 weeks

    Registry description

    Mean systolic blood pressure by treatment and follow-up week

  12. Vital Signs - Weight

    Time frame · Weekly for 6 weeks

    Registry description

    Mean weight (kg) by treatment and follow-up week

  13. Vital Signs - Pulse

    Time frame · Weekly for 6 weeks

    Registry description

    Mean sitting pulse (bpm) by treatment and follow-up week

  14. Simpson-Angus Scale (SAS)

    Time frame · Baseline, week 3, and week 6

    Registry 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.

  15. Abnormal Involuntary Movement Scale (AIMS)

    Time frame · Treatment Week 0 and Week 6

    Registry 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.

  16. Electrocardiogram (EKG)

    Time frame · Once during Evaluation and once at Treatment Week 6

    Registry description

    Mean corrected QT interval (QTc) by study week and treatment.

  17. Barnes Akathisia Scale (BAS) - Global Score

    Time frame · Treatment Week 0 and Week 6

    Registry 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.

  18. Blood Oxytocin Levels

    Time frame · Treatment Week 0 and Week 6

    Registry description

    Blood Oxytocin Levels by Treatment and Visit

  19. Laboratory Measures - ALT/SGPT

    Time frame · Once during evaluation and once at the end of 6 weeks of study treatment

    Registry description

    Alanine transaminase/serum glutamic-pyruvic transaminase (ALT/SGPT) blood levels by treatment group and visit.

  20. Laboratory Measures - AST/SGOT

    Time frame · Once during evaluation and once at the end of 6 weeks of study treatment

    Registry description

    Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) blood levels by treatment group and visit.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Every other week for 6 weeks

Scale for the Assessment of Negative Symptoms (SANS) Total Score

GroupValue (units on a scale)Spread
1: Oxytocin/Placebo-galantamine33.236.91
2: Galantamine/Placebo-oxytocin36.6310.09
3: Placebo-galantamine /Placebo-oxytocin36.6310.61
Primary outcomeMean· Treatment Week 0 and Week 6

Mean Z-Scores for Composite Cognitive Primary Outcome* by Treatment Group and Week

GroupValue (units on a scale)Spread
1: Oxytocin/Placebo-galantamine0.230.92
2: Galantamine/Placebo-oxytocin-0.220.47
3: Placebo-galantamine /Placebo-oxytocin0.210.83
Secondary and other outcome results(6)
Secondary outcomeMean· Every other week for 6 weeks

Scale for the Assessment of Negative Symptoms (SANS) - Avolition

GroupValue (units on a scale)Spread
1: Oxytocin/Placebo-galantamine2.940.90
2: Galantamine/Placebo-oxytocin2.910.88
3: Placebo-galantamine /Placebo-oxytocin2.440.97
Secondary outcomeMean· Every other week for 6 weeks

Scale for the Assessment of Negative Symptoms (SANS) - Anhedonia

GroupValue (units on a scale)Spread
1: Oxytocin/Placebo-galantamine2.420.59
2: Galantamine/Placebo-oxytocin2.600.80
3: Placebo-galantamine /Placebo-oxytocin2.660.69
Secondary outcomeMean· Every other week for 6 weeks

Scale for the Assessment of Negative Symptoms (SANS) - Alogia

GroupValue (units on a scale)Spread
1: Oxytocin/Placebo-galantamine0.600.61
2: Galantamine/Placebo-oxytocin0.950.65
3: Placebo-galantamine /Placebo-oxytocin0.990.69
Secondary outcomeMean· Every other week for 6 weeks

Scale for the Assessment of Negative Symptoms (SANS) - Blunted Affect

GroupValue (units on a scale)Spread
1: Oxytocin/Placebo-galantamine1.670.86
2: Galantamine/Placebo-oxytocin1.961.06
3: Placebo-galantamine /Placebo-oxytocin2.210.97
Secondary outcomeMean· Every other week for 6 weeks

Brief Psychiatric Rating Scale (BPRS) - Total Score

GroupValue (units on a scale)Spread
1: Oxytocin/Placebo-galantamine34.165.66
2: Galantamine/Placebo-oxytocin30.356.66
3: Placebo-galantamine /Placebo-oxytocin32.657.09
Secondary outcomeMean· Every other week for 6 weeks

Brief Psychiatric Rating Scale (BPRS) - Psychosis Score

GroupValue (units on a scale)Spread
1: Oxytocin9.343.20
2: Galantamine7.303.01
3: Placebo8.183.80

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
1: OxytocinOxytocin: 24 IU oxytocin or placebo in a total of 6 puffs (3 puffs per nostril)daily for 6 weeks–0 / 174 / 17
2: GalantamineGalantamine or placebo Galantamine: Galantamine will be dispensed as follows: 4 mg bid x 7 days; 8mg bid x 7days, then 12 mg bid for the last 4 weeks.–1 / 201 / 20
3: PlaceboPlacebo: placebo-Galantamine 1 capsules twice a day and placebo-oxytocin 3 puffs in each nostril once a day.–0 / 210 / 21

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 64 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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