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Lurasidone Effects on Tissue Glutamate in Schizophrenia

Primary Purpose

Schizophrenia, Schizoaffective Disorder

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Lurasidone

Haloperidol

Perphenazine

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring schizophrenia, schizoaffective, cognition, lurasidone, Latuda

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subject at least 18 years old
Subject meets criteria diagnosis of schizophrenia or schizoaffective disorder.
Subject is not pregnant and is not planning pregnancy within the projected duration of the study.
Female subject who is of reproductive potential agrees to remain abstinent or use adequate and reliable contraception throughout the study
Subject is in good physical health on the basis of medical history, physical examination, and laboratory screening.
Eyesight corrected to 20-40 or better
Able to read, speak, and understand English*

Exclusion Criteria:

Any medications being used as mood stabilizers (i.e., anticonvulsants)
Subject currently has a clinically significant medical condition(s) that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study.
Subject demonstrates evidence of acute/chronic hepatitis which is clinically significant
Subject has a history of malignancy < 5 years prior
Subject has a history of neuroleptic malignant syndrome (NMS).
Subject has a history of alcohol or substance abuse within 3 months prior to screening or alcohol or substance dependence within 12 months prior to screening
Subject tests positive for drugs of abuse at screening. In the event a subject tests positive for cannabis, the investigator will evaluate the subject's ability to abstain from cannabis during the study.
Subjects diagnosed with type 1 diabetes
Subject has a prolactin concentration > 200 ng/mL at screening
Subject has a history or presence of abnormal ECG which is clinically significant
Subject has a history of hypersensitivity to more than two distinct chemical classes of drug (e.g., sulfas and penicillins).
Subjects have received depot neuroleptics within 12 weeks prior to randomization.
Subject has a history of treatment with clozapine for refractory psychosis and/or subject has been treated with clozapine within 4 months of randomization.
Subject does not have a stable residence for the 3 months prior to randomization.
Subject requires treatment with any potent CYP3A4 inhibitors or inducers during the study.
Subject has received electroconvulsive therapy (ECT) within 90 days prior to
Subject has been randomized in a prior clinical trial of lurasidone.
History of serious head injury with unconsciousness for >30 minutes

Sites / Locations

UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Lurasidone

Haloperidol

Perphenazine

Arm Description

Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks

Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.

Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.

Outcomes

Primary Outcome Measures

Cerebral Glutamate Levels

Mean values of cerebral glutamate levels was measured by high resolution 3T magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC). Data were acquired from the dorsal anterior cingulate cortex (ACC) using single voxel localized PRESS (TE1, TE2) = (32, 65) ms with an 8-channel head coil in a 3T whole-body scanner (Philips Medical Systems). Voxel size was 30x20x15 mm3 (9 mL) and were placed over the bilateral anterior cingulate cortex (ACC). All values are normalized to water. More negative values represent less cerebral glutamate levels.

Secondary Outcome Measures

Brief Assessments of Cognition in Schizophrenia Scores (BACS)

Mean of cognition was assessed by BACS, which measures neurocognitive function in schizophrenia. BACs is a validated, composite measure of cognition which is used in schizophrenia. It is composed of Verbal memory (range: 0-75), Working memory (range: 0-28), Motor speed (range: 0-100), Verbal Fluency (number of words generated), Information processing (range: 0-110) and Executive functions (range: 0-22). Higher z-scores indicate a better performance and outcome. BACS composite score are represented as z-scores which can be positive or negative. There is no minimum or maximum as this is a continuous measure.

Full Information

NCT ID

NCT02199743

First Posted

July 23, 2014

Last Updated

February 26, 2021

Sponsor

University of Texas Southwestern Medical Center

Collaborators

Sumitomo Pharma America, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02199743

Brief Title

Lurasidone Effects on Tissue Glutamate in Schizophrenia

Official Title

Lurasidone Effects on Tissue Glutamate in Schizophrenia

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

February 2013 (undefined)

Primary Completion Date

June 2016 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Texas Southwestern Medical Center

Collaborators

Sumitomo Pharma America, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

24 individuals with schizophrenia or schizoaffective disorders, who are currently considered stable, will be recruited, screened for entry criteria into a blinded study with a 4-week randomization to either lurasidone, haloperidol, or perphenazine to examine glutamate-related outcomes with lurasidone as compared to haloperidol and perphenazine.

Detailed Description

At study start all volunteers will be discontinued from their current antipsychotic drug (APD) and switched to haloperidol 4mg for 5 days. At the end of this discontinuation period, all baseline symptom ratings and cognition testing will be done, as well as the baseline imaging procedures. At the end of the baseline procedures, volunteers will be blindly randomized, either to lurasidone at 40mg (N=12), or to haloperidol at 4mg/d or perphenazine at 16mg/d (N=12). Doses will increase to 80mg/d lurasidone, 8 mg/d haloperidol, or 32 mg/d of perphenazine at the beginning of week two. Dose should be stable for the last 3 weeks of treatment unless side effects are prominent, then the dose can be decreased to 40 lurasidone/4 haloperidol/16 perphenazine mg/d for optimal clinical management. The randomization strategy will be designed and implemented by the research pharmacist in four blocks of six volunteers; drug will be dispensed by the research pharmacy according to the randomization schedule. The randomization will be followed by a four week treatment period at optimal dose levels. On the last two days of the 4 week stable dosing period, the specified glutamate outcome measures will be completed (neuroimaging and cognitive testing) along with all the symptom outcome measures, testing for drug plasma levels, and usual blood safety measures. Patients will be seen weekly for clinical evaluation; suicidality will be monitored weekly. All medications other than study drugs will be discontinued, as much as possible, for the 24-48 hr assessment period. After the evaluation phase, patients will be cross-titrated back to their original treatment medication and dosing. This design will generate outcomes from 12 patients on lurasidone vs. 12 patients on haloperidol/ perphenazine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia, Schizoaffective Disorder

Keywords

schizophrenia, schizoaffective, cognition, lurasidone, Latuda

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

35 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lurasidone

Arm Type

Active Comparator

Arm Description

Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks

Arm Title

Haloperidol

Arm Type

Active Comparator

Arm Description

Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.

Arm Title

Perphenazine

Arm Type

Active Comparator

Arm Description

Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.

Intervention Type

Drug

Intervention Name(s)

Lurasidone

Other Intervention Name(s)

Latuda

Intervention Description

Compare to haloperidol and perphenazine

Intervention Type

Drug

Intervention Name(s)

Haloperidol

Other Intervention Name(s)

Haldol

Intervention Description

Compare to lurasidone

Intervention Type

Drug

Intervention Name(s)

Perphenazine

Other Intervention Name(s)

Trilafon

Intervention Description

Compare to lurasidone

Primary Outcome Measure Information:

Title

Cerebral Glutamate Levels

Description

Time Frame

Baseline and 4 weeks

Secondary Outcome Measure Information:

Title

Brief Assessments of Cognition in Schizophrenia Scores (BACS)

Description

Time Frame

Baseline and 4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject at least 18 years old Subject meets criteria diagnosis of schizophrenia or schizoaffective disorder. Subject is not pregnant and is not planning pregnancy within the projected duration of the study. Female subject who is of reproductive potential agrees to remain abstinent or use adequate and reliable contraception throughout the study Subject is in good physical health on the basis of medical history, physical examination, and laboratory screening. Eyesight corrected to 20-40 or better Able to read, speak, and understand English* Exclusion Criteria: Any medications being used as mood stabilizers (i.e., anticonvulsants) Subject currently has a clinically significant medical condition(s) that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study. Subject demonstrates evidence of acute/chronic hepatitis which is clinically significant Subject has a history of malignancy < 5 years prior Subject has a history of neuroleptic malignant syndrome (NMS). Subject has a history of alcohol or substance abuse within 3 months prior to screening or alcohol or substance dependence within 12 months prior to screening Subject tests positive for drugs of abuse at screening. In the event a subject tests positive for cannabis, the investigator will evaluate the subject's ability to abstain from cannabis during the study. Subjects diagnosed with type 1 diabetes Subject has a prolactin concentration > 200 ng/mL at screening Subject has a history or presence of abnormal ECG which is clinically significant Subject has a history of hypersensitivity to more than two distinct chemical classes of drug (e.g., sulfas and penicillins). Subjects have received depot neuroleptics within 12 weeks prior to randomization. Subject has a history of treatment with clozapine for refractory psychosis and/or subject has been treated with clozapine within 4 months of randomization. Subject does not have a stable residence for the 3 months prior to randomization. Subject requires treatment with any potent CYP3A4 inhibitors or inducers during the study. Subject has received electroconvulsive therapy (ECT) within 90 days prior to Subject has been randomized in a prior clinical trial of lurasidone. History of serious head injury with unconsciousness for >30 minutes

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carol A Tamminga, M.D.

Organizational Affiliation

UT Southwestern Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UT Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.utsouthwestern.edu/labs/schizophrenia/

Description

Tamminga Lab and Clinic Website

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Lurasidone Effects on Tissue Glutamate in Schizophrenia

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