Effects of Galantamine on Cognition

NCT01100775 | Completed Phase 2 Results DMC

• 2 other identifiers: HP-000449591P50MH082999-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Schizophrenia is a chronic disorder with onset of psychosis occurring in late teen early twenties, with cognitive impairments and negative symptoms frequently emerging much earlier. Such cognitive impairments and negative symptoms but much milder are also observed in high-risk groups (such as relatives of schizophrenia patients), who may or may not develop the full blown psychotic disorder. Our study plans to recruit such non-ill subjects to test the effects of galantamine on clinical/physiological/cognitive measures. This study serves several goals: If a drug is found effective in treating subtle deficits, then it will provide treatment strategy in individuals with schizophrenia spectrum personality disorders and for early intervention in schizophrenia. In addition, one of the difficulties of testing a drug on schizophrenia is that patients take other medications (i.e., antipsychotic drugs) that can change the effects of the test drug. The proposed study will be in subjects who will not be taking antipsychotic medications. Our study will be carried out in two sessions, at least one month apart. Subjects will be randomly assigned to the two possible order of administration: the drug and then placebo, or the placebo and then drug. Subjects will be given a lead-in 3 days of 4mg/ twice a day of galantamine (or placebo) followed by 8 mg (or placebo) on the 4th day, the day of testing. We will administer a battery of clinical/cognitive/neurophysiological tests after the 8 mg drug dose.

Conditions

Schizophrenia

Keywords

Galantamine; Schizophrenia; working memory; cognitive

Outcome Measures

Primary Outcomes (7)

• RVIP Target Hit and False Alarm (Number of Responses)

  Rapid Visual Information Processing (RVIP) measures primarily sustained attention but perhaps also working memory. The task was continuous stimuli presentation of a stream of single digits (from 1 to 9) presented in the center of the computer monitor at a rate of 1/600milliseconds; the subjects respond when the they see a target sequence of 3 odds or 3 evens in consecutive sequence. Two target sequences are separated by a minimum and maximum of 30 non-target digits.

  25 minutes (duration needed to complete this test)

• RVIP Reaction Times (ms)

  Rapid Visual Information Processing (RVIP) measures primarily sustained attention but perhaps also working memory. The task was continuous stimuli presentation of a stream of single digits (from 1 to 9) presented in the center of the computer monitor at a rate of 1/600milliseconds; the subjects respond when the they see a target sequence of 3 odds or 3 evens in consecutive sequence. Two target sequences are separated by a minimum and maximum of 30 non-target digits.

  25 minutes (total duration to test RVIP)

• Trust Game (Dollar Amount Earned)

  Participants compete in a social trust game in which they are paired with a partner (the computer program). Over the course of 24 rounds he participant can offer up to $10 to their partner. The partner can either accept the offer, in which case the total amount offered is split equally between the participant and their partner (i.e. $10 is split into $5 each). Or the partner can reject the offer and receive a portion of the toal offer for themselves and give the participant nothing ($0). The total amount of money that can be offered ranges from $0-240.

  20 minutes (total duration of the trust game cognitive test)

• Brief Assessment of Cognition for Schizophrenia (BACS) Score

  The BACS Symbol Coding subtest will be used to assess processing speed, and the demographically corrected T score, will be used for data analysis. This test requires less than 5 minutes to administer adn provides a highly reliable measure of processing speed. There are nine symbols coded 1 through 9. Participants are given 90 seconds to match a series of these symbols with their corresponding number. The total correct matches in the participants score. Scores range from 0-110.

  5 minutes (duration needed to complete the assessment)

• Hopkins Verbal Learning Test (HVLT) Score

  HVLT comes in 6 different forms. Forms 4 and 5 were used for this study with one form administered on the first day and the other on the second and were counterbalanced between subjects. Each form contains 12 nouns, four words each from one of three semantic categories, to be learned over the course of three learning trials.

  15 minutes (duration needed to complete this test)

• Reading the Mind in the Eyes Score (Number of Correct Responses)

  A 30 item task presents a picture of a person's eyes and the participant is asked to determine the person's mental state from 4 multiple choice options.

  10 minutes (duration needed to complete the test)

• The Brief Smell Identification Test (B-SIT) Score (Number of Correct Responses)

  The Brief Smell Identification Test (B-SIT) is a 5-minute, 12-item screening test. Participants try to identify 12 different odors with four multiple choice options given for each odor.

  5 minutes (duration usually needed to complete this test)

Secondary Outcomes (2)

• Social Affiliation Measured by Social Affiliative Role Play (Rating Scale Score)

  30 minutes (time needed to complete this test)

• Facial Affect Recognition Score (Number of Responses)

  10 minutes (time usually needed to complete this test)

Study Arms (2)

Galantamine, then Placebo

EXPERIMENTAL

Participants took lead-in 3 days of 4mg/ twice a day of galantamine followed by 8 mg on the 4th day, the day of testing. Then, after a period of at least one month, participants took lead-in 3 days of 4mg/ twice a day of placebo followed by 8 mg on the 4th day, the day of testing.

Drug: Galantamine; Drug: Placebo

Placebo, then Galantamine

EXPERIMENTAL

Participants took lead-in 3 days of 4mg/ twice a day of placebo followed by 8 mg on the 4th day, the day of testing. Then, after a period of at least one month, participants took lead-in 3 days of 4mg/ twice a day of galantamine followed by 8 mg on the 4th day, the day of testing.

Drug: Galantamine; Drug: Placebo

Interventions

Galantamine DRUG

A lead-in 3 days of 4mg/ twice a day of galantamine (or placebo) followed by 8 mg (or placebo) on the 4th day, the day of testing.

Also known as: Razadyne, 01RZ437

Galantamine, then Placebo; Placebo, then Galantamine

Placebo DRUG

Subjects will be randomly assigned to the two possible order of administration: the drug and then placebo, or the placebo and then drug. Subjects will be given a lead-in 3 days of 4mg/ twice a day of galantamine (or placebo) followed by 8 mg (or placebo) on the 4th day, the day of testing.

Galantamine, then Placebo; Placebo, then Galantamine

Eligibility Criteria

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

You may qualify if:

• age range of 18-64 (confirmed by drivers license or other form of identification)
• the presence of 3 or more SSP symptoms (at least 2 of the SSP symptoms will be negative symptoms as defined by the schizoid traits)
• the presence of visuospatial working memory impairment as defined by error in the oculomotor delayed response (ODR) task of more than 0.5 SD above the mean values in healthy control subjects
• relative of an individual with schizophrenia, schizoaffective disorder, or schizophreniform disorder
• able to provide written informed consent (ESC score 10 or above)

You may not qualify if:

• subjects meeting criteria for a life-time diagnosis of any one of the DSM IV, Axis I psychotic disorders (exceptions being a single past episode of major depressive disorder with psychotic features or psychotic symptoms associated with substance abuse with the substance abuse ending 6-months prior to study participation) (this is for the SSP recruitment)
• subjects meeting 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
• medical conditions that preclude participation in drug trials or assessments of outcome measures (including significant brain, cardiac, liver, lung, endocrinological or metabolic disorders)
• received any investigational drug in the preceding four weeks
• pregnant or of childbearing age and not using a medically approved form of birth control

Sponsors & Collaborators

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

Study Sites (1)

University of Maryland, Baltimore

Baltimore, Maryland, 21228, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Galantamine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amaryllidaceae Alkaloids; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Ms. Dawn Detamore
• Organization: University of Maryland Baltimore

DDetamore@som.umaryland.edu

410 402 6820

Study Officials

• L. E. Hong, M.D.

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: L. Elliot Hong, M.D.

Study Record Dates

• First Submitted: January 4, 2010
• First Posted: April 9, 2010
• Study Start: May 1, 2010
• Primary Completion: August 21, 2014
• Study Completion: August 21, 2014
• Last Updated: June 8, 2022
• Results First Posted: June 8, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)