Effectiveness RCT of Customized Adherence Enhancement

NCT ID: NCT04622150

Last Updated: 2025-12-16

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

190 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-01

Study Completion Date

2026-06-01

Brief Summary

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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

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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.

Conditions

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Bipolar Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Customized Adherence Enhancement (CAE)

This arm will receive the experimental intervention, Customized Adherence Enhancement (CAE).

Group Type EXPERIMENTAL

Customized Adherence Enhancement (CAE)

Intervention Type BEHAVIORAL

CAE is comprised of a series of up to four treatment modules whose inclusion is determined based upon an individuals reasons for nonadherence (adherence barriers).The standardized modules are Psychoeducation, Modified Motivational Interviewing, Communication with Providers, Medication Routines. CAE participants will have a core series of approximately four sessions spaced about one week apart over a period of 4-6 weeks, and one booster in-person session 4 weeks after the completion of the four core sessions (total of approximately 5 sessions). Sessions 2-4 will be delivered remotely by the study interventionist. All participants will have the first session in-person. The final booster session will be conducted at the sites and will review all previously introduced materials. There will be a follow-up phone call with the study interventionist that will occur in the four-week time period between completion of four CAE core sessions and prior to initiation of the booster CAE session.

Enhanced Treatment as Usual (eTAU)

This arm will receive the control intervention, Enhanced Treatment as Usual (eTAU).

Group Type ACTIVE_COMPARATOR

Enhanced Treatment as Usual (eTAU)

Intervention Type BEHAVIORAL

eTAU participants will receive monthly text messages (or phone calls for participants who prefer not to receive texts) to refill medications, fill eCAPs and brief general adherence promotion messages during the follow-up period.

Interventions

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Customized Adherence Enhancement (CAE)

CAE is comprised of a series of up to four treatment modules whose inclusion is determined based upon an individuals reasons for nonadherence (adherence barriers).The standardized modules are Psychoeducation, Modified Motivational Interviewing, Communication with Providers, Medication Routines. CAE participants will have a core series of approximately four sessions spaced about one week apart over a period of 4-6 weeks, and one booster in-person session 4 weeks after the completion of the four core sessions (total of approximately 5 sessions). Sessions 2-4 will be delivered remotely by the study interventionist. All participants will have the first session in-person. The final booster session will be conducted at the sites and will review all previously introduced materials. There will be a follow-up phone call with the study interventionist that will occur in the four-week time period between completion of four CAE core sessions and prior to initiation of the booster CAE session.

Intervention Type BEHAVIORAL

Enhanced Treatment as Usual (eTAU)

eTAU participants will receive monthly text messages (or phone calls for participants who prefer not to receive texts) to refill medications, fill eCAPs and brief general adherence promotion messages during the follow-up period.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

89 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Case Western Reserve University

OTHER

Sponsor Role lead

Responsible Party

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Martha Sajatovic, MD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martha Sajatovic, MD

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University

Locations

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W.O. Walker Center

Cleveland, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

The Nord Center

Lorain, Ohio, United States

Site Status

Countries

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United States

References

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Sajatovic M, Levin JB, Adeniyi C, Black J, Weise C, Fiorelli N, Kelley E, Einstadter D, Bauer M, Briggs FBS. Association Between Adherence Barriers, Self-Reported Adherence, and Psychiatric Symptoms Among Adults With Bipolar Disorder. Bipolar Disord. 2025 Nov 11. doi: 10.1111/bdi.70067. Online ahead of print.

Reference Type DERIVED
PMID: 41220091 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35927740 (View on PubMed)

Other Identifiers

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R01MH119487

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY20210857

Identifier Type: -

Identifier Source: org_study_id