SchizophreniaPhase 2CIDAR-3NCT01012167
Oxytocin or Galantamine Versus Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia
A Phase 2 study testing Oxytocin and Galantamine in people with Schizophrenia, run by University of Maryland, Baltimore at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Oxytocin and Galantamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 6 sitesUnited States
- Study dates
- Feb 2010to Jul 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Baltimore VA Medical Center
Baltimore, Maryland, 21201
Community Mental Health Centers
Baltimore, Maryland, 21201
Keypoint Community Mental Health Centers
Baltimore, Maryland, 21222
Maryland Psychiatric Research Center
Baltimore, Maryland, 21228
Maryland Psychiatric Research Center
Catonsville, Maryland, 21228
Keypoint Mental health Center
Dundalk, Maryland, 21222
About this study
Official title: Oxytocin or Galantamine vs. Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia
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.
Read more
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.
- Conditions
- Schizophrenia
- Being tested
- Oxytocin, Galantamine, Placebo-Oxytocin, Placebo-Galantamine
- Keywords
- Schizophrenia, oxytocin, galantamine
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxytocinDrug
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
GalantamineDrug
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
Placebo-OxytocinOther
Saline nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration
Placebo-GalantamineOther
Placebo tablets twice a day for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1: galantamine/placebo-oxytocin | Active comparator | Subjects randomized to galantamine will receive galantamine and placebo-oxytocin Receives: Drug: Galantamine; Other: Placebo-Oxytocin |
| 2: oxytocin/placebo-galantamine | Active comparator | Subjects randomized to oxytocin will receive oxytocin and placebo-galantamine Receives: Drug: Oxytocin; Other: Placebo-Galantamine |
| 3: placebo-galantamine /placebo-oxytocin | Placebo comparator | Subjects randomized to placebo will receive placebo-galantamine and placebo-oxytocin Receives: Other: Placebo-Oxytocin; Other: Placebo-Galantamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Treatment Week 0 and Week 6
Secondary outcomes (81)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Weekly for 6 weeks
Vital Signs - Systolic Blood Pressure
Mean systolic blood pressure by treatment and follow-up week
Measured: Weekly for 6 weeks
Vital Signs - Weight
Mean weight (kg) by treatment and follow-up week
Measured: Weekly for 6 weeks
Vital Signs - Pulse
Mean sitting pulse (bpm) by treatment and follow-up week
Measured: 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.
Measured: 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.
Measured: Treatment Week 0 and Week 6
Electrocardiogram (EKG)
Mean corrected QT interval (QTc) by study week and treatment.
Measured: 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.
Measured: Treatment Week 0 and Week 6
Blood Oxytocin Levels
Blood Oxytocin Levels by Treatment and Visit
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
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Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Treatment Week 0 and Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2009 (estimated)
- Study startFeb 2010
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Robert Buchanan, University of Maryland, Baltimore
- Investigators
- William T Carpenter, M.D., Principal investigator, Maryland Psychiatric Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01012167
- Sponsor's protocol ID
- HP-00044324
- Other IDs
- 1P50MH082999-01
- Acronym
- CIDAR-3
- Status last verified
- Jan 2022
- First submitted
- 28 Apr 2009
- Last updated
- 12 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxytocin or Galantamine vs. Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia
- ClinicalTrials.gov ID
- NCT01012167
- Acronym / sponsor ID
- CIDAR-3 / HP-00044324
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, oxytocin, galantamine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Feb 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 11 Nov 2009 (estimated)
- Results
- Posted 2 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1: galantamine/placebo-oxytocin | Active comparator | Drug: Galantamine, Other: Placebo-OxytocinSubjects randomized to galantamine will receive galantamine and placebo-oxytocin |
| 2: oxytocin/placebo-galantamine | Active comparator | Drug: Oxytocin, Other: Placebo-GalantamineSubjects randomized to oxytocin will receive oxytocin and placebo-galantamine |
| 3: placebo-galantamine /placebo-oxytocin | Placebo comparator | Other: Placebo-Oxytocin, Other: Placebo-GalantamineSubjects randomized to placebo will receive placebo-galantamine and placebo-oxytocin |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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:
- The maximum level of psychotic, depressive, and extrapyramidal symptoms at the beginning and end of leading in:
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OxytocinOxytocin: 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 | Drug | 2: oxytocin/placebo-galantamine |
| GalantamineGalantamine: 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 | Drug | 1: galantamine/placebo-oxytocin |
| Placebo-OxytocinSaline nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration | Other | 1: galantamine/placebo-oxytocin, 3: placebo-galantamine /placebo-oxytocin |
| Placebo-GalantaminePlacebo tablets twice a day for 6 weeks | Other | 2: oxytocin/placebo-galantamine, 3: placebo-galantamine /placebo-oxytocin |
Primary outcome
Scale for the Assessment of Negative Symptoms (SANS) Total Score
Time frame: Every other week for 6 weeks
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
Time frame: Treatment Week 0 and Week 6
* 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.
81 secondary outcomes
Scale for the Assessment of Negative Symptoms (SANS) - Avolition
Time frame: Every other week for 6 weeks
Scale for the Assessment of Negative Symptoms (SANS) - Anhedonia
Time frame: Every other week for 6 weeks
Scale for the Assessment of Negative Symptoms (SANS) - Alogia
Time frame: Every other week for 6 weeks
Scale for the Assessment of Negative Symptoms (SANS) - Blunted Affect
Time frame: Every other week for 6 weeks
Brief Psychiatric Rating Scale (BPRS) - Total Score
Time frame: Every other week for 6 weeks
Brief Psychiatric Rating Scale (BPRS) - Psychosis Score
Time frame: Every other week for 6 weeks
Calgary Depression Scale (CDS) - Total Score
Time frame: Every other week for 6 weeks
Arizona Sexual Experience Questionnaire (ASEX) Female
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Arizona Sexual Experience Questionnaire (ASEX) Male
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Vital Signs - Diastolic Blood Pressure
Time frame: Weekly for 6 weeks
Vital Signs - Systolic Blood Pressure
Time frame: Weekly for 6 weeks
Vital Signs - Weight
Time frame: Weekly for 6 weeks
Vital Signs - Pulse
Time frame: Weekly for 6 weeks
Simpson-Angus Scale (SAS)
Time frame: Baseline, week 3, and week 6
Abnormal Involuntary Movement Scale (AIMS)
Time frame: Treatment Week 0 and Week 6
Electrocardiogram (EKG)
Time frame: Once during Evaluation and once at Treatment Week 6
Barnes Akathisia Scale (BAS) - Global Score
Time frame: Treatment Week 0 and Week 6
Blood Oxytocin Levels
Time frame: Treatment Week 0 and Week 6
Laboratory Measures - ALT/SGPT
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - AST/SGOT
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Alkaline Phosphatase
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Calcium
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Sodium
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Potassium
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Chloride
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - CO2
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Cholesterol
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - HDL
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - LDL
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Triglycerides
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - VLDL
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Glucose
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Albumin
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Globulin
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - A/G Ratio
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Bilirubin
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - Protein
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Laboratory Measures - BUN
Time frame: Once during evaluation and once at the end of 6 weeks of study treatment
Side Effect Checklist (SEC) - Abdominal Pain
Time frame: Weekly for 6 weeks
Side Effect Checklist (SEC) - Anorexia
Time frame: Weekly for 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William T Carpenter, M.D. principal investigator
Maryland Psychiatric Research Center
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oxytocin and Galantamine in people with Schizophrenia, run by University of Maryland, Baltimore at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Scale for the Assessment of Negative Symptoms (SANS) Total Score (time frame: Every other week for 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2022.