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CRT-Guanfacine for SPD

Primary Purpose

Schizotypal Personality Disorder, SPD

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Cognitive Remediation Therapy

Guanfacine

Placebo

About this trial

This is an interventional treatment trial for Schizotypal Personality Disorder focused on measuring Schizotypal Personality Disorder, SPD, cognitive remediation therapy, CRT, guanfacine, cognitive impairment, working memory, pharmacological cognitive enhancing agent, neuropsychological testing, schizophrenia spectrum disorders, Personality Disorders

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Willing and having capacity to provide informed consent
Currently meeting DSM-IV-TR criteria for Schizotypal Personality Disorder
Males and females between the ages of 18-65
Medically healthy: no major or partially treated medical condition that, based on the judgment of the clinician, would either put the patient at increased risk and/or affect our findings.
Neurologically healthy: no brain injury or head trauma associated with loss of consciousness, seizures, or other conditions that may have caused functional impairment.
At least two weeks free of medication while participating in this study
Score at least one standard deviation below normative means on at least one test in the cognitive battery.
At least 2 weeks free of psychotropic medication while participating in this study. Medication such as NSAIDS (e.g. Advil), Tylenol, Levothyroxine (if on stable dose 1 month, no symptoms of hypothyroidism and normal thyroid labs), non-centrally acting antihistamines, H2 blockers (e.g. Zantac), PPIs (e.g. Prilosec, Prevacid), and others that do not impact cognitive functioning will be allowed; the study physician will evaluate any medication at the time of the medical clearance on a case by case basis.

Exclusion Criteria:

Meet criteria for bipolar I disorder, schizophrenia, schizoaffective disorder, or any other psychotic disorder Clinically significant cardiovascular or neurological conditions, uncontrolled hypertension, clinically significant EKG abnormalities, or serious general medial illness
Current substance abuse or have met criteria for substance dependence within the last 6 months (excluding nicotine)
Currently meeting DSM-IV-TR criteria for Major Depressive Disorder, not better accounted for and secondary to a personality disorder
Currently taking psychotropic medications
Currently taking any medications (systemic or otherwise) that the study physician determines could interfere with the study medication and put the participant at risk and/or interfere with the data
Currently pregnant or lactating
Non-English speaking

Sites / Locations

Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Cognitive Remediation Therapy and placebo

Guanfacine and CRT

Arm Description

7.5 weeks of twice weekly cognitive remediation sessions

7.5 weeks of twice weekly cognitive remediation sessions with 8 weeks of guanfacine

Outcomes

Primary Outcome Measures

MATRICS Consensus Cognitive Battery Score

Change in score at 7.5 weeks as compared to baseline. MATRICS Consensus Cognitive Battery: Subjects will complete the following MATRICS cognitive assessments. The dependent variable (DV) is the total MATRICS battery score. Trail Making Test (TMT): Part A Brief Assessment of Cognition in Schizophrenia: Symbol Coding (BACS SC) Hopkins Verbal Learning Test-Revised (HVLT-R) Weschler Memory Scale-III: Spatial Span Letter Number Span (LNS) Neuropsychological Assessment Battery (NAB): Mazes Brief Visuospatial Memory Test-Revised (BVMT-R) Category Fluency: Animal Naming

Secondary Outcome Measures

Modified version of AX-Continuous Performance Test (AX-CPT) Score

Change in score at 7.5 weeks as compared to baseline. This modified AX-CPT assesses context processing, a domain that has been shown to be impaired in both schizophrenia and SPD.

UCSD Performance Based Skills Assessment (UPSA) Score

Change in score at 7.5 weeks as compared to baseline. The UPSA is an office based test to measure competence at performing day-to-day tasks in five domains: household chores, communication, finance, transportation, and planning recreational activities.

Social Skills Performance Assessment (SSPA) Score

Change in score at 7.5 weeks as compared to baseline. The SSPA is an office based test designed to measure social competence.

Reading of the Mind in the Eyes Score

Change in score at 7.5 weeks as compared to baseline. This is a measure of adult "mentalising", the ability to attribute mental states to oneself or another person.

Full Information

NCT ID

NCT02524899

First Posted

August 10, 2015

Last Updated

February 24, 2017

Sponsor

Icahn School of Medicine at Mount Sinai

Collaborators

Brain & Behavior Research Foundation

1. Study Identification

Unique Protocol Identification Number

NCT02524899

Brief Title

CRT-Guanfacine for SPD

Official Title

Guanfacine Enhancement of Working Memory: Prospects for Augmenting Cognitive Remediation in the Schizophrenia Spectrum

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Completed

Study Start Date

January 2014 (undefined)

Primary Completion Date

January 10, 2017 (Actual)

Study Completion Date

January 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Icahn School of Medicine at Mount Sinai

Collaborators

Brain & Behavior Research Foundation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a study to assess the efficacy augmenting cognitive remediation therapy (CRT) with a pharmacological agent for individuals with schizotypal personality disorder (SPD). Impaired cognition, along with functional and social skill deficits, is a core feature of schizophrenia and schizophrenia spectrum disorders. A better understanding of the cognitive and functional impairments in schizophrenia-related conditions, as well as the identification of interventions that can reduce these impairments, are vital to improving outcomes for individual with these disorders.

Detailed Description

This study proposes to 1) evaluate the effects of 7.5 weeks of twice weekly cognitive remediation sessions, combined with concurrent administration of 8 weeks of guanfacine/placebo, on performance on cognitive, functional, and social skills performance measures in a sample of SPD patients with proven deficits in these areas. 2) Compare the effect of cognitive remediation therapy + 8 weeks guanfacine with cognitive remediation therapy + placebo on cognition in this schizophrenia spectrum disorder population. 3) Further characterize cognitive impairment in SPD using specific tests of working memory to evaluate the relationship between working memory and functional and social skill outcomes in this population. The study hypothesizes that: While both groups (those receiving CRT + guanfacine or CRT +placebo) will demonstrate improvements in overall cognitive functioning, SPD participants receiving CRT + guanfacine will evidence greater increases in post-treatment performance on our primary outcome measures-MATRICS battery total score, AX-CPT, N-Back, PASAT and DOT Test- particularly in areas related to working memory. Participants receiving CRT + guanfacine will also demonstrate greater improvements in functional and social functioning exploratory measures, as evidenced by performance on our secondary assessments, the UPSA, SSPA, MASC, and Reading of the Mind in the Eyes.

6. Conditions and Keywords

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

Schizotypal Personality Disorder, SPD

Keywords

Schizotypal Personality Disorder, SPD, cognitive remediation therapy, CRT, guanfacine, cognitive impairment, working memory, pharmacological cognitive enhancing agent, neuropsychological testing, schizophrenia spectrum disorders, Personality Disorders

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cognitive Remediation Therapy and placebo

Arm Type

Active Comparator

Arm Description

7.5 weeks of twice weekly cognitive remediation sessions

Arm Title

Guanfacine and CRT

Arm Type

Experimental

Arm Description

7.5 weeks of twice weekly cognitive remediation sessions with 8 weeks of guanfacine

Intervention Type

Behavioral

Intervention Name(s)

Cognitive Remediation Therapy

Other Intervention Name(s)

CRT

Intervention Description

Cognitive Remediation Therapy (CRT) will consist of fifteen 45-minute, twice weekly sessions over 7.5 weeks. During each session, subjects, seated at a desk in a private interview room in our research office suite, will work through exercises that are part of the Psychological Software Services CogReHab program. The software to be used is a multimedia, Windows-based program that consists of exercises aimed at improving areas of deficit within the schizophrenia spectrum, such as executive function, working memory, and social cognition.

Intervention Type

Drug

Intervention Name(s)

Guanfacine

Intervention Description

After completing baseline cognitive testing, subjects will be randomized to guanfacine or placebo. Subjects in the active treatment arm will begin with a guanfacine dose of 0.5mg/day and be titrated up to a maximum of 2mg/day according to our well-tolerated protocol in schizophrenia subjects. The dosing schedule of active guanfacine will be as follows: 0.5mg/d for week 1, 1.0mg/d for week 2, 1.0 mg bid for weeks 3, 4, 5, 6, and 7 and 1.0mg/d for week 8.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

After completing baseline cognitive testing, subjects will be randomized to guanfacine or placebo. Subjects in placebo arm will have matching schedule as active arm.

Primary Outcome Measure Information:

Title

MATRICS Consensus Cognitive Battery Score

Description

Time Frame

Baseline and 7.5 weeks after randomization

Secondary Outcome Measure Information:

Title

Modified version of AX-Continuous Performance Test (AX-CPT) Score

Description

Change in score at 7.5 weeks as compared to baseline. This modified AX-CPT assesses context processing, a domain that has been shown to be impaired in both schizophrenia and SPD.

Time Frame

Baseline and 7.5 weeks after randomization

Title

UCSD Performance Based Skills Assessment (UPSA) Score

Description

Time Frame

Baseline and 7.5 weeks after randomization

Title

Social Skills Performance Assessment (SSPA) Score

Description

Change in score at 7.5 weeks as compared to baseline. The SSPA is an office based test designed to measure social competence.

Time Frame

Baseline and 7.5 weeks after randomization

Title

Reading of the Mind in the Eyes Score

Description

Change in score at 7.5 weeks as compared to baseline. This is a measure of adult "mentalising", the ability to attribute mental states to oneself or another person.

Time Frame

Baseline and 7.5 weeks after randomization

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: Willing and having capacity to provide informed consent Currently meeting DSM-IV-TR criteria for Schizotypal Personality Disorder Males and females between the ages of 18-65 Medically healthy: no major or partially treated medical condition that, based on the judgment of the clinician, would either put the patient at increased risk and/or affect our findings. Neurologically healthy: no brain injury or head trauma associated with loss of consciousness, seizures, or other conditions that may have caused functional impairment. At least two weeks free of medication while participating in this study Score at least one standard deviation below normative means on at least one test in the cognitive battery. At least 2 weeks free of psychotropic medication while participating in this study. Medication such as NSAIDS (e.g. Advil), Tylenol, Levothyroxine (if on stable dose 1 month, no symptoms of hypothyroidism and normal thyroid labs), non-centrally acting antihistamines, H2 blockers (e.g. Zantac), PPIs (e.g. Prilosec, Prevacid), and others that do not impact cognitive functioning will be allowed; the study physician will evaluate any medication at the time of the medical clearance on a case by case basis. Exclusion Criteria: Meet criteria for bipolar I disorder, schizophrenia, schizoaffective disorder, or any other psychotic disorder Clinically significant cardiovascular or neurological conditions, uncontrolled hypertension, clinically significant EKG abnormalities, or serious general medial illness Current substance abuse or have met criteria for substance dependence within the last 6 months (excluding nicotine) Currently meeting DSM-IV-TR criteria for Major Depressive Disorder, not better accounted for and secondary to a personality disorder Currently taking psychotropic medications Currently taking any medications (systemic or otherwise) that the study physician determines could interfere with the study medication and put the participant at risk and/or interfere with the data Currently pregnant or lactating Non-English speaking

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Margaret McNamara McClure, Ph.D.

Organizational Affiliation

Icahn School of Medicine at Mount Sinai

Official's Role

Principal Investigator

Facility Information:

Facility Name

Icahn School of Medicine at Mount Sinai

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

16950221

Citation

McClure MM, Barch DM, Romero MJ, Minzenberg MJ, Triebwasser J, Harvey PD, Siever LJ. The effects of guanfacine on context processing abnormalities in schizotypal personality disorder. Biol Psychiatry. 2007 May 15;61(10):1157-60. doi: 10.1016/j.biopsych.2006.06.034. Epub 2006 Sep 1.

Results Reference

background

PubMed Identifier

16626941

Citation

Reichenberg A, Weiser M, Rapp MA, Rabinowitz J, Caspi A, Schmeidler J, Knobler HY, Lubin G, Nahon D, Harvey PD, Davidson M. Premorbid intra-individual variability in intellectual performance and risk for schizophrenia: a population-based study. Schizophr Res. 2006 Jul;85(1-3):49-57. doi: 10.1016/j.schres.2006.03.006. Epub 2006 Apr 19.

Results Reference

background

PubMed Identifier

15796677

Citation

Heinrichs RW. The primacy of cognition in schizophrenia. Am Psychol. 2005 Apr;60(3):229-42. doi: 10.1037/0003-066X.60.3.229.

Results Reference

background

PubMed Identifier

11522468

Citation

Friedman JI, Adler DN, Temporini HD, Kemether E, Harvey PD, White L, Parrella M, Davis KL. Guanfacine treatment of cognitive impairment in schizophrenia. Neuropsychopharmacology. 2001 Sep;25(3):402-9. doi: 10.1016/S0893-133X(01)00249-4.

Results Reference

background

PubMed Identifier

10192826

Citation

Jakala P, Riekkinen M, Sirvio J, Koivisto E, Kejonen K, Vanhanen M, Riekkinen P Jr. Guanfacine, but not clonidine, improves planning and working memory performance in humans. Neuropsychopharmacology. 1999 May;20(5):460-70. doi: 10.1016/S0893-133X(98)00127-4.

Results Reference

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CRT-Guanfacine for SPD

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