NCT02524899

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jan 2014

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2014

Completed
1.6 years until next milestone

First Submitted

Initial submission to the registry

August 10, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

August 17, 2015

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 10, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 10, 2017

Completed
Last Updated

February 28, 2017

Status Verified

February 1, 2017

Enrollment Period

3 years

First QC Date

August 10, 2015

Last Update Submit

February 24, 2017

Conditions

Schizotypal Personality DisorderSPD

Keywords

Schizotypal Personality DisorderSPDcognitive remediation therapyCRTguanfacinecognitive impairmentworking memorypharmacological cognitive enhancing agentneuropsychological testingschizophrenia spectrum disordersPersonality Disorders

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

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

    Baseline and 7.5 weeks after randomization

  • UCSD Performance Based Skills Assessment (UPSA) Score

    Baseline and 7.5 weeks after randomization

  • Social Skills Performance Assessment (SSPA) Score

    Baseline and 7.5 weeks after randomization

  • Reading of the Mind in the Eyes Score

    Baseline and 7.5 weeks after randomization

Study Arms (2)

Cognitive Remediation Therapy and placebo

ACTIVE COMPARATOR

7.5 weeks of twice weekly cognitive remediation sessions

Behavioral: Cognitive Remediation TherapyDrug: Placebo

Guanfacine and CRT

EXPERIMENTAL

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

Behavioral: Cognitive Remediation TherapyDrug: Guanfacine

Interventions

Cognitive Remediation TherapyBEHAVIORAL

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.

Also known as: CRT
Cognitive Remediation Therapy and placeboGuanfacine and CRT
GuanfacineDRUG

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.

Guanfacine and CRT
PlaceboDRUG

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

Cognitive Remediation Therapy and placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (5)

  • 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.

    PMID: 16950221BACKGROUND

  • 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.

    PMID: 16626941BACKGROUND

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

    PMID: 15796677BACKGROUND

  • 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.

    PMID: 11522468BACKGROUND

  • 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.

    PMID: 10192826BACKGROUND

MeSH Terms

Conditions

Schizotypal Personality DisorderCognitive DysfunctionPersonality Disorders

Interventions

Guanfacine

Condition Hierarchy (Ancestors)

Mental DisordersCognition DisordersNeurocognitive Disorders

Intervention Hierarchy (Ancestors)

GuanidinesAmidinesOrganic ChemicalsPhenylacetatesAcids, CarbocyclicCarboxylic Acids

Study Officials

  • Margaret McNamara McClure, Ph.D.

    Icahn School of Medicine at Mount Sinai

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

August 10, 2015

First Posted

August 17, 2015

Study Start

January 1, 2014

Primary Completion

January 10, 2017

Study Completion

January 10, 2017

Last Updated

February 28, 2017

Record last verified: 2017-02

Locations

US(1)