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

NCT ID: NCT01012167

Last Updated: 2022-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2014-07-31

Brief 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. 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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1: galantamine/placebo-oxytocin

Subjects randomized to galantamine will receive galantamine and placebo-oxytocin

Group Type: ACTIVE_COMPARATOR

Galantamine

Intervention Type: DRUG

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-Oxytocin

Intervention Type: OTHER

Saline nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration

2: oxytocin/placebo-galantamine

Subjects randomized to oxytocin will receive oxytocin and placebo-galantamine

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: DRUG

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

Placebo-Galantamine

Intervention Type: OTHER

Placebo tablets twice a day for 6 weeks

3: placebo-galantamine /placebo-oxytocin

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

Group Type: PLACEBO_COMPARATOR

Placebo-Oxytocin

Intervention Type: OTHER

Saline nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration

Placebo-Galantamine

Intervention Type: OTHER

Placebo tablets twice a day for 6 weeks

Interventions

Oxytocin

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

Galantamine

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: DRUG

Placebo-Oxytocin

Saline nasal spray with a total of 6 puffs of the spray, 3 in each nostril at each administration

Intervention Type: OTHER

Placebo-Galantamine

Placebo tablets twice a day for 6 weeks

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Robert Buchanan

Chief, Maryland Psychiatric Research Center, Outpatient Research Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William T Carpenter, M.D.

Role: PRINCIPAL_INVESTIGATOR

Maryland Psychiatric Research Center

Locations

Baltimore VA Medical Center

Baltimore, Maryland, United States

Community Mental Health Centers

Baltimore, Maryland, United States

Keypoint Community Mental Health Centers

Baltimore, Maryland, United States

Maryland Psychiatric Research Center

Baltimore, Maryland, United States

Maryland Psychiatric Research Center

Catonsville, Maryland, United States

Keypoint Mental health Center

Dundalk, Maryland, United States

Countries

United States

Other Identifiers

1P50MH082999-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HP-00044324

Identifier Type: -

Identifier Source: org_study_id