CRT-Guanfacine for SPD

Schizotypal Personality Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02524899
• Other study ID #: GCO 13-0109
• Status: Completed
• Phase: Phase 2
• First received: August 10, 2015
• Last updated: February 24, 2017
• Start date: January 2014
• Est. completion date: January 10, 2017

Study information

• Verified date: February 2017
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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:

1. 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.

2. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: January 10, 2017
• Est. primary completion date: January 10, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Personality Disorders
• Schizotypal Personality Disorder
• SPD

Intervention

Behavioral:
• Cognitive Remediation Therapy
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.

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

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	Brain & Behavior Research Foundation

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

Heinrichs RW. The primacy of cognition in schizophrenia. Am Psychol. 2005 Apr;60(3):229-42. Review. — View Citation

Jäkälä P, Riekkinen M, Sirviö 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline and 7.5 weeks after randomization
Secondary	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.	Baseline and 7.5 weeks after randomization
Secondary	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.	Baseline and 7.5 weeks after randomization
Secondary	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.	Baseline and 7.5 weeks after randomization
Secondary	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.	Baseline and 7.5 weeks after randomization