Clinical trial NCT04622150: Effectiveness RCT of Customized Adherence Enhancement
Official title: Effectiveness RCT of Customized Adherence Enhancement
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bipolar Disorder
Lead sponsor: Case Western Reserve University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2020-11-09
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Approximately one in two individuals with bipolar disorder (BD) are non-adherent with medication, often leading to severe and negative consequences. Unfortunately, there is no widely used evidence-based approach to target poor adherence among individuals with BD. Building upon positive efficacy trial results, the proposed project will test the effectiveness of technology-facilitated Customized Adherence Enhancement (CAE) vs. enhanced treatment as usual (eTAU) using a prospective randomized controlled design in public mental health care settings and preferentially enrolling poorly adherent/high-risk individuals with BD. Deliverables include a curriculum-driven adherence enhancement approach that can be implemented in public healthcare settings and which can improve outcomes for the most vulnerable groups of people with BD.

Detailed description: A cornerstone of treatment uniformly recommended for individuals with bipolar disorder (BD) is mood stabilizing medication. However, approximately one in two individuals with BD are non-adherent with medication, often leading to severe and negative consequences. Unfortunately, there is no widely used evidence-based approach to target poor adherence in BD.

Customized Adherence Enhancement (CAE), developed by this study team, is a brief, practical BD-specific approach that identifies individual adherence barriers and then targets these areas for intervention using a flexibly-administered modular format. A prospective, 6-month, randomized controlled efficacy trial (RCT) of CAE vs. a rigorous control, BD-specific education (EDU) found that medication adherence and functional status were improved in CAE vs. EDU for poorly-adherent patients. Remarkably, the benefits of CAE occurred in individuals who had been living with BD, on average, for over 2 decades. While promising, the original efficacy RCT was limited by the fact that it was performed in an academic medical center, did not make use of existing web/text messaging technology, and did not address potential challenges to scale-up in standard clinical settings.

In response to PA-18-722 "Improving Patient Adherence to Treatment and Prevention Regimens to Promote Health", this Type 1 hybrid effectiveness-implementation project will adapt CAE for use in community/public-sector care settings, test effectiveness in high-risk, poorly adherent individuals in these settings, and gather evidence on barriers and facilitators to implementation of the intervention in order to inform subsequent scale-up. The project will examine putative mechanistic engagement targets suggested by previous work and include implementation elements that will inform future dissemination should findings be positive. The project will be implemented in 4 specific aims: 1) Refine the CAE intervention guided by stakeholders at a community mental health clinic (CMHC) and a safety-net county healthcare system, 2) Test the effectiveness of technology-facilitated CAE vs. enhanced treatment as usual (eTAU) using a prospective, 2-site RCT, 3) Test the effects of CAE vs. eTAU on functional status in poorly adherent individuals with BD, and 4) Identify barriers and facilitators to CAE implementation in order to inform subsequent scale-up and spread using qualitative methods and guided by implementation conceptual models. Additional exploratory analysis will assess whether changes in patient-level adherence barriers and facilitators mediate the treatment effects on adherence. Finally, the project will evaluate on-site (outpatient visits, no-show rates) and off-site (emergency department visits, hospitalizations) health resource use to help characterize relative value and inform future sustainability efforts. An over-arching goal of this project will be to provide a curriculum-driven adherence enhancement approach that can be implemented in public-sector care settings and which can improve outcomes for the most vulnerable groups of people with BD.

Eligibility criteria: Patients receiving care at the Nord Center, MetroHealth system, and other not-for-profit health systems.

Inclusion Criteria:

1. Participants will have a diagnosis of Bipolar Disorder Type I or Type II determined by the Structured Clinical Interview for DSM-5 patient version (SCID-P).
2. Have had BD for at least two years duration
3. Have received treatment with at least one evidence-based medication to stabilize mood for at least six months (lithium, anticonvulsant, or antipsychotic mood stabilizer)
4. Yes to either of the following questions:

   1. Do you ever have any trouble taking all of your medications? Or
   2. Do you ever try to cope on your own without medication?
5. a BPRS ≥ 36 or YRMS ≥8 or MADRS ≥8
6. Be able to participate in psychiatric interviews and give written informed consent
7. Have their own cellular phone in order to receive text messages as part of the intervention

Exclusion Criteria:

1. Unable or unwilling to participate in psychiatric interviews. This will include individuals, who may be too psychotic to participate in interviews/rating scales
2. Unable or unwilling to give written, informed consent to study participation
3. Individuals who participated in Phase 1 of the study
4. Children under the age of 18
5. Individuals at high risk for suicide who cannot be safely managed in their current treatment setting

Primary outcomes:
measure: Change from baseline in the Tablet Routine Questionaire (TRQ) "past week" item at 12 months
timeFrame: Baseline and 12 Months
measure: Change from baseline in the Tablet Routine Questionaire (TRQ) "past month" item at 12 months
timeFrame: Baseline and 12 Months
measure: Change from baseline in treatment adherence as measured by electronic pill monitoring (eCAPS) at 12 months
timeFrame: Baseline and 12 Months
Secondary outcomes:
measure: change in Global Assessment of Functioning (GAF)
timeFrame: Baseline and 12 Months
measure: change in Brief Psychiatric Rating Scale (BPRS)
timeFrame: Baseline and 12 Months
measure: change in Young Mania Rating Scale (YMRS)
timeFrame: Baseline and 12 Months
measure: change in Montgomery Asberg Depression Rating Scale (MADRS)
timeFrame: Baseline and 12 Months
measure: change in Clinical Global Impressions Scale (CGI)
timeFrame: Baseline and 12 Months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: W.O. Walker Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Lorain
country: United States
facility: The Nord Center
state: Ohio
Study officials:
affiliation: Case Western Reserve University
name: Martha Sajatovic, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Levin JB, Briggs F, Blixen C, Bauer M, Einstadter D, Albert JM, Weise C, Woods N, Fuentes-Casiano E, Cassidy KA, Rentsch J, Sarna K, Sajatovic M. A randomized controlled trial of customized adherence enhancement (CAE-E): study protocol for a hybrid effectiveness-implementation project. Trials. 2022 Aug 4;23(1):634. doi: 10.1186/s13063-022-06517-0.