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

NCT01012167 | Completed Phase 2 Results DMC

• 2 other identifiers: HP-000443241P50MH082999-01
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 6

Brief Summary

The project is designed to address the following two primary aims:

• 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

Keywords

Schizophrenia, oxytocin, galantamine

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Treatment Week 0 and Week 6

Secondary Outcomes (81)

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

  Every other week for 6 weeks

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

  Every other week for 6 weeks

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

  Every other week for 6 weeks

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

  Every other week for 6 weeks

• Brief Psychiatric Rating Scale (BPRS) - Total Score

  Every other week for 6 weeks

Study Arms (3)

1: galantamine/placebo-oxytocin

ACTIVE COMPARATOR

Subjects randomized to galantamine will receive galantamine and placebo-oxytocin

Drug: Galantamine; Other: Placebo-Oxytocin

2: oxytocin/placebo-galantamine

ACTIVE COMPARATOR

Subjects randomized to oxytocin will receive oxytocin and placebo-galantamine

Drug: Oxytocin; Other: Placebo-Galantamine

3: placebo-galantamine /placebo-oxytocin

PLACEBO COMPARATOR

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

Other: Placebo-Oxytocin; Other: Placebo-Galantamine

Interventions

Oxytocin 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

2: oxytocin/placebo-galantamine

Galantamine 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

1: galantamine/placebo-oxytocin

Placebo-Oxytocin OTHER

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

1: galantamine/placebo-oxytocin; 3: placebo-galantamine /placebo-oxytocin

Placebo-Galantamine OTHER

Placebo tablets twice a day for 6 weeks

2: oxytocin/placebo-galantamine; 3: placebo-galantamine /placebo-oxytocin

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (6)

Baltimore VA Medical Center

Baltimore, Maryland, 21201, United States

Location

Community Mental Health Centers

Baltimore, Maryland, 21201, United States

Location

Keypoint Community Mental Health Centers

Baltimore, Maryland, 21222, United States

Location

Maryland Psychiatric Research Center

Baltimore, Maryland, 21228, United States

Location

Maryland Psychiatric Research Center

Catonsville, Maryland, 21228, United States

Location

Keypoint Mental health Center

Dundalk, Maryland, 21222, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Oxytocin; Galantamine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Amaryllidaceae Alkaloids; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: William Carpenter, Jr.
• Organization: Maryland Psychiatric Research Center

wcarpent@mprc.umaryland.edu

410-402-7101

Study Officials

• William T Carpenter, M.D.

  Maryland Psychiatric Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Maryland Psychiatric Research Center, Outpatient Research Program

Study Record Dates

• First Submitted: April 28, 2009
• First Posted: November 11, 2009
• Study Start: February 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: January 12, 2022
• Results First Posted: June 2, 2017

Record last verified: 2022-01

Locations

US (6)