Clinical trial NCT04815239: Early Intervention for Youth at High Risk for Bipolar Disorder
Official title: Early Intervention for Youth at High Risk for Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bipolar Disorder
Keywords: psychosocial treatment
early intervention
prevention
adolescent
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2021-03-24
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Risk for Subthreshold or Threshold Manic Episodes
timeFrame: 18 months
measure: Rate of Subthreshold or Threshold Manic Symptoms
timeFrame: 18 months
measure: Severity of Affective lability
timeFrame: 18 months
Secondary outcomes:
measure: Total sleep time (Objective)
timeFrame: 18 months
measure: Total sleep time (subjective)
timeFrame: 18 months
measure: Sleep variability (objective)
timeFrame: 18 months
measure: Sleep variability (subjective)
timeFrame: 18 months
Other outcomes:
measure: Exploratory: Association between actigraphy and passive sensing-derived measures of sleep-wake
timeFrame: 18 months
Locations:
city: Pittsburgh
country: United States
facility: Nicole Arnold
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Tina R Goldstien, PhD
role: PRINCIPAL_INVESTIGATOR
References: