Early Intervention for Youth at High Risk for Bipolar Disorder

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Early Intervention for Youth at High Risk for Bipolar Disorder

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Behavioral: Interpersonal and Social Rhythm Therapy (IPSRT)
* Behavioral: The Healthy Lifestyle Behavior Intervention (HL)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Interpersonal and Social Rhythm Therapy (IPSRT)<br>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)<br>* 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.<br>|
| Active Comparator: Healthy Lifestyle Intervention (HL)<br>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)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Severity of Affective lability | Children's Affective Lability Scale (CALS; Range 0-80) | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psychosocial treatment, early intervention, prevention, adolescent