Family-Focused Therapy for Individuals at High Clinical Risk for Psychosis: A Confirmatory Efficacy Trial

NCT ID: NCT04338152

Last Updated: 2026-01-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-15

Study Completion Date

2026-12-31

Brief Summary

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The present study is a confirmatory efficacy trial of Family Focused Therapy for youth at clinical high risk for psychosis (FFT-CHR). This trial is sponsored by seven mature CHR clinical research programs from the North American Prodrome Longitudinal Study (NAPLS). The young clinical high risk sample (N = 220 youth ages 13-25) is to be followed at 6-month intervals for 18 months.

Detailed Description

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This randomized, single blind trial will compare outcomes from a 6-month FFT-CHR intervention and a control condition (enhanced care, or EC) matched to the FFT-CHR in duration (6 months) and access to a clinician. Participants families in FFT-CHR are provided 18 family sessions augmented by a therapy app with content and surveys, while participants in the EC condition are provided three family sessions plus five monthly individual support and case management sessions. Duration of therapy sessions is one hour.

Main Goals of FFT-CHR (Experimental Treatment)

1. To assist young clients and their family in: developing a common understanding of CHR symptoms; recognizing early signs of escalating symptoms; practicing individual and family coping strategies; and pre-planning family responses to any escalation in symptoms. When families have poor understanding of CHR symptoms and strategies for their management, this can fuel stressful home dynamics and contribute to youth withdrawal and decompensation.
2. For the youth and their family members to learn to express more constructive messages during their interactions, particularly regarding highly charged topics such as curbing risky behaviors and management of the offspring's symptoms.
3. For youth and family members to practice skills for resolving family or extrafamilial conflicts (usually those related to the youth's functioning) through effective communication and problem solving

The control condition, Enhanced Care (EC) shares the psychoeducation goal of FFT-CHR but is more oriented toward skill-training for the individual patient. Whereas it does not offer the same level of opportunity for families to build communication and problem-solving skills, the family is actively involved in helping the individual develop a relapse prevention plan. Monthly individual sessions focus on the development of individual coping skills such as symptom tracking and problem-solving. Both conditions require families to submit real-time mobile app surveys to assist with progress tracking.

Study Aims

The primary clinical outcomes are prodromal positive symptom scores examined immediately after treatment (6 months) and at 18 months. Secondary outcomes are time to remission of positive symptoms and psychosocial functioning over 18 months. Temporal relationships between early changes in treatment targets and later changes in symptoms or psychosocial functioning will also be examined.

Primary Hypotheses

1. FFT-CHR (vs. EC) will be associated with greater improvement in positive symptoms by end of therapy and follow-up (6 and 18 months), and greater high-risk syndrome remission and better psychosocial functioning at 18 months
2. FFT-CHR (vs. EC) will be associated with greater improvement in family communication and problem solving at 6 months
3. FFT-CHR (vs. EC) will be associated with greater improvement in youth-perceived parental criticism at 6 months. In turn, improvements in family communication, problem-solving and youths' perceptions of criticism will be associated with downstream improvements in the youths' primary outcomes (positive symptoms) and secondary outcomes (time to remission and psychosocial functioning) over 18 months. Thus, improvements in family functioning are hypothesized to mediate the relationship between treatment condition (FFT-CHR, EC) and changes in primary and secondary outcomes in the individual with CHR syndrome.
4. CHR individuals with higher baseline risk of conversion are hypothesized to improve more on family communication over 6 months and primary and secondary outcomes over 18 months in FFT-CHR than in EC.

Conditions

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Psychotic Disorders Prodromal Symptoms Prodromal Schizophrenia Psychosis Family

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

FFT-CHR assists families with (1) recognizing the youth's psychosis risk symptoms and warning signs of escalating risk, (2) understanding vulnerability to psychosis and interventions, and (3) operating effectively as a unit. The manual includes session instructions and handouts.

The Enhanced care (EC) condition has also been manualized and tested as a family educational treatment in CHR and bipolar youth. The 3 weekly sessions involve an abridged form of FFT-CHR psychoeducation. Then the youth has monthly individual sessions focused on applying the prevention plan and nondirective problem-solving of conflicts. The clinician serves as case manager.

See further description below.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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FFT-CHR

Family-Focused Therapy for Clinical High-Risk Individuals

Group Type EXPERIMENTAL

Family Focused Therapy for Clinical High Risk Youth (FFT-CHR)

Intervention Type BEHAVIORAL

Family-Focused Therapy (FFT) has been tested in randomized trials involving persons with bipolar disorder, depression, and clinical high-risk syndromes. FFT-CHR provides families with psychoeducation (sessions 1-6) about prodromal symptoms and the role of the family in helping maintain stability. Clients are supported in building coping skills and monitoring thoughts, perceptions, and mood. The family formulates a prevention action plan to prevent prodromal symptoms from escalating into full episodes. Communication training (sessions 7-13) teaches families to express positive and negative feelings, listen actively, make positive requests for change, and communicate clearly through role-playing and between-session practice. In problem solving (sessions 14-18) participants learn to break down problems into smaller ones, evaluate pros/cons, and choose solutions to implement.

Enhanced Care

Enhanced Care Psychoeducation for Clinical High-Risk Individuals

Group Type ACTIVE_COMPARATOR

Enhanced Care (EC)

Intervention Type BEHAVIORAL

Enhanced care (EC) has been tested as a family educational treatment in CHR and bipolar youth. The first 3 sessions of EC involve the CHR person and family (parents, siblings) and cover the same content as the psychoeducational module of FFT in abridged form. The objective of these sessions is to develop a prevention action plan. Then, the CHR person is offered monthly individual sessions with the same clinician over the next 5 months, for a total of 8 sessions over 6 months. The individual sessions focus on applying the prevention action plan when symptoms emerge, and supportive, nondirective problem-solving regarding areas of conflict with family, with peers or in the educational or occupational arena. The clinician also serves as case manager.

Interventions

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Family Focused Therapy for Clinical High Risk Youth (FFT-CHR)

Family-Focused Therapy (FFT) has been tested in randomized trials involving persons with bipolar disorder, depression, and clinical high-risk syndromes. FFT-CHR provides families with psychoeducation (sessions 1-6) about prodromal symptoms and the role of the family in helping maintain stability. Clients are supported in building coping skills and monitoring thoughts, perceptions, and mood. The family formulates a prevention action plan to prevent prodromal symptoms from escalating into full episodes. Communication training (sessions 7-13) teaches families to express positive and negative feelings, listen actively, make positive requests for change, and communicate clearly through role-playing and between-session practice. In problem solving (sessions 14-18) participants learn to break down problems into smaller ones, evaluate pros/cons, and choose solutions to implement.

Intervention Type BEHAVIORAL

Enhanced Care (EC)

Enhanced care (EC) has been tested as a family educational treatment in CHR and bipolar youth. The first 3 sessions of EC involve the CHR person and family (parents, siblings) and cover the same content as the psychoeducational module of FFT in abridged form. The objective of these sessions is to develop a prevention action plan. Then, the CHR person is offered monthly individual sessions with the same clinician over the next 5 months, for a total of 8 sessions over 6 months. The individual sessions focus on applying the prevention action plan when symptoms emerge, and supportive, nondirective problem-solving regarding areas of conflict with family, with peers or in the educational or occupational arena. The clinician also serves as case manager.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

1. Participants must be able to understand and sign an informed consent (or assent for minors) document in English;
2. Youth has at least one parent or legal guardian who participants sees often enough (minimum 4 hours/week) that family intervention is sensible, who is English-speaking, and who consents to study participation and treatment sessions; and
3. Youth currently meets criteria for clinical high-risk (CHR) for psychosis, with attenuated positive symptoms that have begun or worsened in the past 12 months, genetic risk and deterioration, or brief intermittent psychotic symptoms. Eligible participants may meet DSM-5 criteria for any non-psychotic disorder (e.g. major depression, anxiety disorders, ADHD), as long as the disorder does not clearly account for the presence of psychosis risk symptoms.

Exclusion Criteria

1. Current or lifetime Axis 1 psychotic disorder by DSM-5 criteria
2. Impaired intellectual functioning (IQ\<70)
3. Unwilling or unable to taper individual therapy to monthly by start of treatment
4. Past or current history of a clinically significant medical or central nervous system disorder that may contribute to CHR symptoms or confound assessment
5. Severe substance or alcohol use disorder within the past 6 months, and/or substance use (including cannabis) is causally related to recent onset of CHR symptoms so as to confound prodromal diagnostic determination.

If either an exclusionary medical condition or an incidental medical condition is suspected, the participant will be advised to consult with their physician or will be referred to a specialist. Eligibility for the trial will be reconsidered if the medical condition has been treated to remission and the subject still meets CHR criteria.
Minimum Eligible Age

13 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role lead

Responsible Party

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David J. Miklowitz, Ph.D.

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David J. Miklowitz, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Carrie E. Bearden, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Kristin S. Cadenhead, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Scott Woods, M.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Jean M. Addington, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Michelle Friedman-Yakoobian, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Harvard Medical School/Massachusetts Mental Health Center

Andrea M. Auther, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Zucker Hillside Hospital at Hofstra / Northwell Health

Barbara A. Cornblatt, Ph.D., M.B.A.

Role: PRINCIPAL_INVESTIGATOR

Hofstra University / Northwell Health

Daniel H. Mathalon, Ph.D., M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Holly K. Hamilton, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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University of California, Los Angeles

Los Angeles, California, United States

Site Status

University of California, San Diego

San Diego, California, United States

Site Status

University of California, San Francisco School of Medicine

San Francisco, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Harvard University/Beth Israel Deconess Medical Center

Boston, Massachusetts, United States

Site Status

Zucker Hillside Hospital

New York, New York, United States

Site Status

University of Calgary

Calgary, Alberta, Canada

Site Status

Countries

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United States Canada

References

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O'Brien MP, Zinberg JL, Ho L, Rudd A, Kopelowicz A, Daley M, Bearden CE, Cannon TD. Family problem solving interactions and 6-month symptomatic and functional outcomes in youth at ultra-high risk for psychosis and with recent onset psychotic symptoms: a longitudinal study. Schizophr Res. 2009 Feb;107(2-3):198-205. doi: 10.1016/j.schres.2008.10.008. Epub 2008 Nov 8.

Reference Type BACKGROUND
PMID: 18996681 (View on PubMed)

Miklowitz DJ, Chung B. Family-Focused Therapy for Bipolar Disorder: Reflections on 30 Years of Research. Fam Process. 2016 Sep;55(3):483-99. doi: 10.1111/famp.12237. Epub 2016 Jul 29.

Reference Type BACKGROUND
PMID: 27471058 (View on PubMed)

Marvin SE, Miklowitz DJ, O'Brien MP, Cannon TD. Family-focused therapy for individuals at clinical high risk for psychosis: treatment fidelity within a multisite randomized trial. Early Interv Psychiatry. 2016 Apr;10(2):137-43. doi: 10.1111/eip.12144. Epub 2014 Apr 11.

Reference Type BACKGROUND
PMID: 24725329 (View on PubMed)

Miklowitz DJ, O'Brien MP, Schlosser DA, Addington J, Candan KA, Marshall C, Domingues I, Walsh BC, Zinberg JL, De Silva SD, Friedman-Yakoobian M, Cannon TD. Family-focused treatment for adolescents and young adults at high risk for psychosis: results of a randomized trial. J Am Acad Child Adolesc Psychiatry. 2014 Aug;53(8):848-58. doi: 10.1016/j.jaac.2014.04.020. Epub 2014 Jun 2.

Reference Type BACKGROUND
PMID: 25062592 (View on PubMed)

O'Brien MP, Miklowitz DJ, Candan KA, Marshall C, Domingues I, Walsh BC, Zinberg JL, De Silva SD, Woodberry KA, Cannon TD. A randomized trial of family focused therapy with populations at clinical high risk for psychosis: effects on interactional behavior. J Consult Clin Psychol. 2014 Feb;82(1):90-101. doi: 10.1037/a0034667. Epub 2013 Nov 4.

Reference Type BACKGROUND
PMID: 24188511 (View on PubMed)

O'Brien MP, Miklowitz DJ, Cannon TD. Decreases in perceived maternal criticism predict improvement in subthreshold psychotic symptoms in a randomized trial of family-focused therapy for individuals at clinical high risk for psychosis. J Fam Psychol. 2015 Dec;29(6):945-51. doi: 10.1037/fam0000123. Epub 2015 Jul 13.

Reference Type BACKGROUND
PMID: 26168262 (View on PubMed)

Salinger JM, O'Brien MP, Miklowitz DJ, Marvin SE, Cannon TD. Family communication with teens at clinical high-risk for psychosis or bipolar disorder. J Fam Psychol. 2018 Jun;32(4):507-516. doi: 10.1037/fam0000393. Epub 2018 Feb 1.

Reference Type BACKGROUND
PMID: 29389150 (View on PubMed)

Cornblatt BA, Auther AM, Niendam T, Smith CW, Zinberg J, Bearden CE, Cannon TD. Preliminary findings for two new measures of social and role functioning in the prodromal phase of schizophrenia. Schizophr Bull. 2007 May;33(3):688-702. doi: 10.1093/schbul/sbm029. Epub 2007 Apr 17.

Reference Type BACKGROUND
PMID: 17440198 (View on PubMed)

Other Identifiers

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1R01MH123575-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20-002102

Identifier Type: -

Identifier Source: org_study_id

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