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

Condition(s) targeted: Schizophrenia

Intervention: Oxytocin (Drug); Galantamine or placebo Galantamine (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Maryland

Official(s) and/or principal investigator(s):
William T Carpenter, M.D., Principal Investigator, Affiliation: University of Maryland

Overall contact:
Jennifer Osing, M.A., Phone: 410-402-6060, Email: josing@mprc.umaryland.edu

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.

Official title: Oxytocin or Galantamine vs. Placebo for the Treatment of Negative Symptoms and Cognitive Impairments in Schizophrenia

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Scale for the Assessment of Negative Symptoms (SANS) total score

Neurocognitive assessment battery composite score

Secondary outcome:

P-50 Testing

Eye Tracking measures

Brief Psychiatric Rating Scale (BPRS)

Calgary Depression Scale (CDS)

Clinical Global Impressions (CGI)

Arizona Sexual Experience Questionnaire ASEX

Likert-type Scale for Social Engagement

Simpson-Angus Scale (SAS)

MPRC-TD scale

Barnes Akathisia Scale (BAS)

Fagerstrom Test of Nicotine Dependence (FTND)

Side Effect Checklist (SEC)

Vital Signs

EKG

Laboratory measures

Minimum age: 18 Years. Maximum age: 64 Years. Gender(s): Both.

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

Jennifer Osing, M.A., Phone: 410-402-6060, Email: josing@mprc.umaryland.edu

Baltimore VA Medical Center, Baltimore, Maryland 21201, United States; Recruiting
Kimberly Sauer, Phone: 410-637-1427, Email: Kimberly.Sauer@va.gov
Robert W Buchanan, M.D., Principal Investigator

Community Mental Health Centers, Baltimore, Maryland 21201, United States; Recruiting
Alec Duggan, Phone: 410-402-7205, Email: aduggan@mprc.umaryland.edu
Guni Thaker, M.D., Principal Investigator

Keypoint Community Mental Health Centers, Baltimore, Maryland 21222, United States; Recruiting
Alec Duggan, Phone: 410-402-7205, Email: aduggan@mprc.umaryland.edu
Robert W Buchanan, M.D., Principal Investigator

Maryland Psychiatric Research Center, Baltimore, Maryland 21228, United States; Recruiting
Christine Brown, Phone: 410-402-7878, Email: cbrown@mprc.umaryland.edu

Maryland Psychiatric Research Center, Catonsville, Maryland 21228, United States; Recruiting
Kelli Sullivan, Phone: 410-402-6412, Email: ksullivan@mprc.umaryland.edu
Robert Buchanan, M.D., Principal Investigator
Ikwunga Wonodi, M.D., Sub-Investigator
L. E. Hong, M.D., Sub-Investigator
William T Carpenter, MD, Principal Investigator
James Gold, PhD, Principal Investigator
Deanna Kelly, PharmD, Principal Investigator

Keypoint Mental health Center, Dundalk, Maryland 21222, United States; Recruiting
Alec Duggan, Phone: 410-402-7205, Email: aduggan@mprc.umaryland.edu
Robert W Buchanan, M.D., Principal Investigator

Starting date: February 2010
Last updated: November 19, 2012