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Oxytocin or Galantamine Versus Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia (CIDAR-3)

This study is currently recruiting participants.
Verified November 2012 by University of Maryland
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
William Carpenter, MD, University of Maryland
ClinicalTrials.gov Identifier:
NCT01012167
First received: April 28, 2009
Last updated: November 19, 2012
Last verified: November 2012
History of Changes
  Purpose

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.

Condition Intervention Phase
Schizophrenia
 Drug: Oxytocin
Drug: Galantamine or placebo Galantamine
Drug: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Oxytocin or Galantamine vs. Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia

Resource links provided by NLM:

MedlinePlus related topics: Schizophrenia
U.S. FDA Resources

Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Scale for the Assessment of Negative Symptoms (SANS) total score [ Time Frame: Weekly for 6 weeks ] [ Designated as safety issue: No ]
  • Neurocognitive assessment battery composite score [ Time Frame: Once during evaluation and once at the end of 6 weeks of study treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • P-50 Testing [ Time Frame: Once during evaluation and once at the end of 6 weeks of study treatment ] [ Designated as safety issue: No ]
  • Eye Tracking measures [ Time Frame: Once during evaluation and once at the end of 6 weeks of study treatment ] [ Designated as safety issue: No ]
  • Brief Psychiatric Rating Scale (BPRS) [ Time Frame: Weekly for 6 weeks ] [ Designated as safety issue: Yes ]
  • Calgary Depression Scale (CDS) [ Time Frame: Weekly for 6 weeks ] [ Designated as safety issue: Yes ]
  • Clinical Global Impressions (CGI) [ Time Frame: Weekly for 6 weeks ] [ Designated as safety issue: Yes ]
  • Arizona Sexual Experience Questionnaire ASEX [ Time Frame: Once during evaluation and once at the end of 6 weeks of study treatment ] [ Designated as safety issue: No ]
  • Likert-type Scale for Social Engagement [ Time Frame: Once during evaluation and once at the end of 6 weeks of study treatment ] [ Designated as safety issue: No ]
  • Simpson-Angus Scale (SAS) [ Time Frame: Baseline, week 3, and week 6 ] [ Designated as safety issue: Yes ]
  • MPRC-TD scale [ Time Frame: Baseline, week 3, and week 6 ] [ Designated as safety issue: Yes ]
  • Barnes Akathisia Scale (BAS) [ Time Frame: Baseline, week 3, and week 6 ] [ Designated as safety issue: Yes ]
  • Fagerstrom Test of Nicotine Dependence (FTND) [ Time Frame: Once during evaluation and once at the end of 6 weeks of study treatment ] [ Designated as safety issue: No ]
  • Side Effect Checklist (SEC) [ Time Frame: Weekly for 6 weeks ] [ Designated as safety issue: Yes ]
  • Vital Signs [ Time Frame: Weekly for 6 weeks ] [ Designated as safety issue: Yes ]
  • EKG [ Time Frame: Once during evaluation and once at the end of 6 weeks of study treatment ] [ Designated as safety issue: Yes ]
  • Laboratory measures [ Time Frame: Once during evaluation and once at the end of 6 weeks of study treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 140
Study Start Date: February 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1: Oxytocin Drug: Oxytocin
24 IU oxytocin or placebo in a total of 6 puffs (3 puffs per nostril)daily for 6 weeks
Active Comparator: 2: Galantamine Drug: Galantamine 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.
Placebo Comparator: 3: Placebo Drug: Placebo
placebo-Galantamine 1 capsules twice a day and placebo-oxytocin 3 puffs in each nostril once a day.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 affective flattening OR SANS alogia global item scores 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 current alcohol or substance dependence (other than nicotine) within the last 6 months or DSM-IV criteria for alcohol or substance abuse (other than nicotine) within the last month.
  • Participants with a DSM-IV diagnosis of Major Depressive Disorder within last 6 months will also be excluded.
  • Participants may be treated with one or more antipsychotics, except clozapine, 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 treated with olanzapine doses greater than 20 mg will be also excluded, because of concerns about its anticholinergic properties at higher doses.
  • Participants may not be treated with anticholinergic medications or have clinically significant extrapyramidal symptoms.

  • Female participants who are pregnant, planning to become pregnant or breastfeeding will be excluded since oxytocin may induce labor. In addition, women of childbearing age are required to use an effective form of birth control for the duration of the study. Effective forms of birth control include:

    1. hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones),
    2. surgical sterility (tubal ligation or hysterectomy)
    3. IUD
    4. Diaphragm with spermicide
    5. Condom with spermicide
  • Participants will not have been randomized to Galantamine in a previous clinical trial at the Maryland Psychiatric Research Center
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01012167

Contacts
Contact: Jennifer Osing, M.A. 410-402-6060 josing@mprc.umaryland.edu
Contact: Christine Brown 410-402-7878 cbrown@mprc.umaryland.edu

Locations
United States, Maryland
Baltimore VA Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Kimberly Sauer     410-637-1427     Kimberly.Sauer@va.gov    
Principal Investigator: Robert W Buchanan, M.D.            
Community Mental Health Centers Recruiting
Baltimore, Maryland, United States, 21201
Contact: Alec Duggan     410-402-7205     aduggan@mprc.umaryland.edu    
Principal Investigator: Guni Thaker, M.D.            
Keypoint Community Mental Health Centers Recruiting
Baltimore, Maryland, United States, 21222
Contact: Alec Duggan     410-402-7205     aduggan@mprc.umaryland.edu    
Principal Investigator: Robert W Buchanan, M.D.            
Maryland Psychiatric Research Center Recruiting
Baltimore, Maryland, United States, 21228
Contact: Christine Brown     410-402-7878     cbrown@mprc.umaryland.edu    
Maryland Psychiatric Research Center Recruiting
Catonsville, Maryland, United States, 21228
Contact: Kelli Sullivan     410-402-6412     ksullivan@mprc.umaryland.edu    
Principal Investigator: Robert Buchanan, M.D.            
Sub-Investigator: Ikwunga Wonodi, M.D.            
Sub-Investigator: L. E. Hong, M.D.            
Principal Investigator: William T Carpenter, MD            
Principal Investigator: James Gold, PhD            
Principal Investigator: Deanna Kelly, PharmD            
Keypoint Mental health Center Recruiting
Dundalk, Maryland, United States, 21222
Contact: Alec Duggan     410-402-7205     aduggan@mprc.umaryland.edu    
Principal Investigator: Robert W Buchanan, M.D.            
Sponsors and Collaborators
University of Maryland
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: William T Carpenter, M.D. University of Maryland
  More Information

No publications provided

Responsible Party: William Carpenter, MD, Director, Maryland Psychiatric Research Center, Outpatient Research Program, University of Maryland
ClinicalTrials.gov Identifier: NCT01012167     History of Changes
Other Study ID Numbers: HP-00044324, 1P50MH082999-01
Study First Received: April 28, 2009
Last Updated: November 19, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Maryland:
Schizophrenia, oxytocin, galantamine

Additional relevant MeSH terms:
Schizophrenia
Cognition Disorders
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Galantamine
Oxytocin
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
 Pharmacologic Actions
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Oxytocics
Reproductive Control Agents

ClinicalTrials.gov processed this record on May 23, 2013