Early Intervention for Youth at High Risk for Bipolar Disorder (KEY)

Investigators will conduct a confirmatory efficacy trial of Interpersonal and Social Rhythm Therapy (IPSRT) delivered via telehealth for offspring of bipolar parents (OBP; age 12-18, n=120) at elevated risk for BP onset via risk calculator score. All participants receive a baseline clinical assessment of psychiatric symptoms and sleep disturbance (via objective and subjective methods), followed by a feedback session. Youth are then randomized to receive 8 sessions of IPSRT or a manualized Healthy Lifestyle Behaviors Program (HL) delivered via secure videoconference. As clinically indicated, youth are offered Community Treatment Referral (CTR) for any psychiatric symptoms/disorders identified at intake. Primary outcome domains over 18 months include mania and affective lability. Investigators will also further investigate the hypothesized mechanism underlying IPSRT (i.e., sleep/circadian disruption) across levels of analysis, and the contribution of interpersonal stress to sleep/circadian disruptions. Application of Implementation Science methods throughout maximizes ultimate scalability and feasibility if efficacious. Investigators will also examine whether passive cellphone sensing may serve as a portable, cost-effective measure of mechanisms and outcomes to enhance ultimate dissemination.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Disorder
• Intervention / Treatment: Behavioral: Interpersonal and Social Rhythm Therapy (IPSRT); Behavioral: The Healthy Lifestyle Behavior Intervention (HL)

Detailed Description

The most potent risk factor for the development of bipolar disorder (BP) is a first-degree family member with the illness; individuals with family history typically experience early BP onset and severe course. Up to 25% of offspring of parents with BP (OBP) develop BP by young adulthood. Using longitudinal data from the Pittsburgh Bipolar Offspring Study (BIOS MH60952), investigators developed a clinical tool ("risk calculator") that reliably predicts an individual OBP's 5-year risk for BP using a subset of demographic and clinical variables. This innovation offers the ideal opportunity to identify OBP at greatest risk and deliver indicated preventive interventions. Yet, to date, there is no evidence-based intervention for OBP who have not already developed mood disorder. Per the experimental therapeutics framework, promising approaches should be informed by, and target, factors that cause and sustain illness. Evidence suggests the pathway to develop BP among biologically vulnerable youth involves sleep and circadian disturbances. Investigators adapted Interpersonal and Social Rhythm Therapy (IPSRT), an evidence-based treatment for BP adults that helps stabilize sleep/ circadian patterns, for adolescent OBP. In an open pilot and subsequent R34 randomized trial (MH091177), Investigators established a preliminary efficacy signal for IPSRT with OBP. Investigators' data further indicate IPSRT, but not Community Treatment Referral (CTR), engages and alters the hypothesized mechanism of action--sleep/ circadian disturbance, although practical barriers impacted treatment attendance. This proposal represents a vital next step in this program of research: a confirmatory efficacy trial of IPSRT delivered via telehealth for OBP (age 12-18, n=120) at elevated risk for BP onset via risk calculator score. All participants receive a baseline clinical assessment of psychiatric symptoms and sleep disturbance (via objective and subjective methods), followed by a feedback session. Youth are then randomized to receive 8 sessions of IPSRT or a manualized Healthy Lifestyle Behaviors Program (HL) delivered via secure videoconference to enhance attendance and reach. As clinically indicated, youth are offered CTR for any psychiatric symptoms/disorders identified at intake. Primary outcome domains over 18 months include mania and affective lability--2 potent near-term predictors of BP in OBP that are themselves associated with morbidity and impairment. Investigators will also further investigate the hypothesized mechanism underlying IPSRT-sleep/circadian disruption--across levels of analysis using reliable, cost-effective methods (actigraphy and daily diary ratings), and the contribution of interpersonal stress to sleep/circadian disruptions. Application of Implementation Science methods throughout maximizes ultimate scalability and feasibility if efficacious. Investigators will also examine whether passive cellphone sensing may serve as a portable, cost-effective measure of mechanisms and outcomes to enhance ultimate dissemination. Research in this area has the potential to prevent, delay, or ameliorate the progression of this chronic and devastating illness in those at highest risk.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pamala Pyle; Email: pylep2@upmc.edu
• Study Contact Backup: Name: Nicole Arnold, MA; Phone Number: 412-246-5796; Email: arnoldne@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Nicole Arnold
      • Contact: Pamala Pyle; Phone Number: 412-246-5686; Email: pylep2@upmc.edu
      • Principal Investigator: Tina R Goldstein, PhD
      • Contact: Nicole Arnold, MA; Phone Number: 412-246-5796; Email: arnoldne@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 12-18 years
• A parent with a diagnosis of BP I or II
• Baseline Risk Calculator score>0.05;
• Able/willing to give informed consent/assent

Exclusion Criteria:

• A lifetime diagnosis of BP I or II
• Current unstabilized psychiatric symptoms
• Evidence of developmental disorder or central nervous system disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Interpersonal and Social Rhythm Therapy (IPSRT); Interpersonal and Social Rhythm Therapy (IPSRT) for at-risk offspring includes 8 sessions over 6 months delivered via secure telemedicine platform. The basis of the intervention is the treatment manual iteratively developed and tested in close consultation with content experts during our open pilot study and R34.The intervention focuses on education about BP risk, stabilizing sleep and daily routines and interpersonal relationships.	Behavioral: Interpersonal and Social Rhythm Therapy (IPSRT); Interpersonal and Social Rhythm Therapy (IPSRT) is an evidence-based treatment for BP adults that prevents or delays mood episodes by stabilizing sleep and daily routines.
Active Comparator: Healthy Lifestyle Intervention (HL); HL is based on the treatment manual developed in a prior trial for adults and adolescents with BP. HL includes psychoeducational modules that aim to teach patients about health risks and help them achieve a balanced lifestyle to optimize physical and mental health. In HL, patients are taught to develop and maintain an individualized lifestyle plan and provided support and encouragement for making progress toward their goals. HL clinicians will deliver 8 sessions over 6 months via secure telehealth platform.	Behavioral: The Healthy Lifestyle Behavior Intervention (HL); HL includes structured psychoeducational modules that aim to teach patients about health risks and help them achieve a balanced lifestyle to optimize physical and mental health.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Affective lability	Children's Affective Lability Scale (CALS; Range 0-80)	18 months
Risk for Subthreshold or Threshold Manic Episodes	Adolescent Longitudinal Interval Follow-Up Evaluation (ALIFE) Psychiatric Status Ratings (PSR; Range 1-6)	18 months
Rate of Subthreshold or Threshold Manic Symptoms	Kiddie Schedule for Affective Disorders and Schizophrenia-Mania Rating Scale (KMRS; Range 0-64)	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total sleep time (Objective)	Actigraphy-derived mean total sleep time	18 months
Total sleep time (subjective)	Daily diary-derived mean total sleep time	18 months
Sleep variability (objective)	Actigraphy-derived sleep variability	18 months
Sleep variability (subjective)	Daily diary-derived sleep variability	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Association between actigraphy and passive sensing-derived measures of sleep-wake	Association between actigraphy and passive sensing-derived measures of sleep-wake	18 months

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Tina R Goldstien, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: adolescent; prevention; early intervention; psychosocial treatment
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder
• Other Study ID Numbers: STUDY21010149; R01MH125971 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In order to gain access to data from this project, outside Investigators must submit a detailed proposal of the study aims, hypotheses to be tested, variables/constructs and analytic approach to be used. Prior to the receipt of data, outside investigators would be required to sign a data sharing agreement and confidentiality statement that stipulates a commitment to: a) using the data for the stated research purposes only; b) securing the data using appropriate computer technology; c) not manipulating the data in order to identify participants; d) destroying or returning the data after analyses are completed. No data can be transferred to other researchers who have not submitted a formal request to the study PIs.
• IPD Sharing Time Frame: Data will be available for addressing other research questions (i.e., those that are not described in funding/pending grants) as soon as the data have been checked for accuracy (a period that will be no later than 1 year after the completion of each assessment). After the award has ended, the study team will continue to test the stated aims but will continue to solicit collaborations with outside researchers and to consider data requests in a timely manner.
• IPD Sharing Access Criteria: When all prerequisites have been met, access to data will be provided through the NDCT Data Access Committee (DAC). Only Investigators and Institutions who have met security measures and have submitted a Data Use Certification co-signed by the PI and the designated Institutional Official at the NIH-recognized sponsoring institution with a current Federal Wide Assurance will be given access. Outside Investigators will be asked to acknowledge the grant that supported the data collection and management in all publications and presentations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No