A Trial of Functional Remediation in Patients With Bipolar Disorder

Efficacy of Functional Remediation on Cognitive and Psychosocial Functioning in Patients With Bipolar Disorder: a Randomized Controlled Trial

In the last decade several evidences show that cognitive impairment is a major feature of bipolar disorder (BD), that is strongly associated with patients' functional outcome. The most affected cognitive domains in BD are attention, memory and executive functions. BD represents a mental illness of considerable therapeutic complexity and the fight against cognitive and functional deterioration have contributed to increase the interest in the development of specific therapeutic strategies.There is the need of new non-pharmacological interventions in BD in order to improve not only affective symptoms, but also cognitive dysfunctions, with the final goal to achieve full functional recovery. The present study is focused on Functional Remediation (FR), a novel group intervention created by the Bipolar Disorder Unit of the Hospital Clinic of Barcelona and designed specifically for bipolar patients, based on a neuro-cognitive-behavioural approach. It involves neurocognitive and psychoeducation techniques (21 weekly sessions). The present study aims to assess FR efficacy in improving cognitive deficits and psychosocial functioning in a sample of euthymic patients with BD, compared to standard treatment (TAU). This is a randomized and rater-blind trial, involving 54 adult out-patients diagnosed with BD I or II (DSM-5 criteria) and clinically stable for at least two months. Patients will be assessed at baseline, post-treatment and 6-months follow-up, on validated cognitive, clinical and functional rating scales. The main result expected is that patients receiving FR will show better cognitive and psychosocial performance, further confirming the preliminary evidence on the utility of FR as an element of standard care for BD patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Bipolar Disorder
• Intervention / Treatment: Behavioral: Functional Remediation; Other: Treatment as usual

Detailed Description

The main objective of this randomized, rater-blind controlled trial is to evaluate the efficacy of Functional Remediation (FR) in improving functional, clinical and cognitive outcomes in euthymic and clinically stable patients with Bipolar Disorder.

FR is a novel group-based intervention, based on a neurocognitive-behavioural approach, making use of ecological techniques, specifically developed for patients with Bipolar Disorder and aimed at restoring psychosocial functioning in this population.

The study will involve subjects recruited from outpatient clinics (residential or semi-residential care) within the Department of Mental Health and Addiction Services of ASST Spedali Civili, Brescia, Italy.

Study participants will be assigned via central randomization to either FR or treatment as usual, the latter consisting of evidence-based drug treatment and case management.

Pharmacological treatment will be maintained stable during the course of the trial, but no restriction will be applied in terms of access to evidence-based non-pharmacological interventions.

Efficacy of the study intervention (lasting 6 months) will be assessed at post-treatment, and later investigated at 6-months follow-up.

The study will be conducted in accordance with the ethical principles of the Declaration of Helsinki and Good Clinical Practice. It will take place within an experimental project related to the "PhD Course in Biomedical Sciences and Translational Medicine", curriculum "Neuroscience" of the University of Brescia, Italy.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Antonio Vita, Prof; Phone Number: +39 0303995233; Email: antonio.vita@unibs.it
• Study Contact Backup: Name: Vivian Accardo, Psy; Phone Number: +39 3474892946; Email: v.accardo@unibs.it

Study Locations

• Italy
  • BS
    • Brescia, BS, Italy, 25133
      • Department of Mental Health and Addiction Services
      • Contact: Vivian Accardo, Psy; Phone Number: +39 3474892946; Email: v.accardo@unibs.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a clinical diagnosis of Bipolar Disorder, type I or II, as referred from treating psychiatrist, confirmed at recruitment using the Structured Clinical Interview for Disorder for DSM-5, Clinical Version (SCID-5-CV);
• Clinically stable (in euthymic phase, defined as Y-MRS <= 6 points + HAM-D <= 8 points) for at least 2 months;
• Aged from 18 to 55 years, with no restriction in terms of gender or ethnicity
• With a minimum education level of 8 years;
• Fluent in Italian language;
• Giving written informed consent to study participation.

Exclusion Criteria:

• Intellectual disability (according to DSM-5 criteria);
• Any medical condition that may affect neuropsychological performance (such as neurological diseases);
• Any comorbid psychiatric condition (including current alcohol and/or drug abuse - up to 3 months before screening)
• Pregnancy;
• Inability to provide informed consent/ withdrawal of consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Functional Remediation	Behavioral: Functional Remediation; Functional Remediation is a manualized, group-based psychosocial intervention built on a neurocognitive-behavioural approach, involving modeling techniques, role-playing tasks, self-instruction, positive reinforcement and metacognitive cues (Vieta E et al, Cambridge University Press, 2014). It consists of 21 90-min weekly sessions, in which a trained therapist and co-therapist work with 10-12 patients: the first 3 sessions are dedicated to psychoeducation on neurocognitive deficits; then 13 sessions of neurocognitive training sequentially target attention, memory and executive functions domains, comprising exercises carried out individually, in pairs or in small groups; the last 5 sessions focus on skills training (communication, interpersonal relationships, autonomy, stress management). Content of the sessions involves ecological tasks adapted to real-world situations, and to-be-performed in two contexts (clinical and daily). Homework is assigned, collected and discussed each time.
Other: Control; Treatment as usual	Other: Treatment as usual; Standard care for bipolar disorders according to good clinical practice, including drug therapy and individual case management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychosocial functioning	Functional outcome will be rated using the Functioning Assessment Short Test (FAST) - Italian Version (Barbato et al., 2013)	Baseline to post-treatment (6 months)
Psychosocial functioning	Functional outcome will be rated using the Functioning Assessment Short Test (FAST) - Italian Version (Barbato et al., 2013)	Baseline to follow-up (12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive performance	Neurocognitive performance will be tested using a complete neuropsychological battery specifically developed for patients with bipolar disorder: the Brief Assessment of Cognition in Affective Disorders (BAC-A) (Keefe et al., 2014), Italian normative data (Rossetti et al. 2019)	Baseline to post-treatment (6 months)
Neurocognitive performance	Neurocognitive performance will be tested using a complete neuropsychological battery specifically developed for patients with bipolar disorder: the Brief Assessment of Cognition in Affective Disorders (BAC-A) (Keefe et al., 2014), Italian normative data (Rossetti et al. 2019)	Baseline to follow-up (12 months)
Socio-cognitive performance/Emotional processing	Social cognition will be evaluated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), Italian version (Curci et al, 2003)	Baseline to post-treatment (6 months)
Socio-cognitive performance/Emotional processing	Social cognition will be evaluated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), Italian version (Curci et al, 2003)	Baseline to follow-up (12 months)
Subthreshold manic symptoms	Manic symptoms will be evaluated using the Young Mania Rating Scale (Y-MRS) (Young et al, 1978). Euthymia will be defined by a score of Y-MRS <= 6 points.	Baseline to post-treatment (6 months)
Subthreshold manic symptoms	Manic symptoms will be evaluated using the Young Mania Rating Scale (Y-MRS) (Young et al, 1978). Euthymia will be defined by a score of Y-MRS <= 6 points.	Baseline to follow-up (12 months)
Subthreshold depressive symptoms	Depressive symptoms will be evaluated using the Hamilton Depression Rating Scale (HAM-D) (Hamilton et al, 1960). Euthymia will be defined by a score of HAM-D <= 8 points.	Baseline to post-treatment (6 months)
Subthreshold depressive symptoms	Depressive symptoms will be evaluated using the Hamilton Depression Rating Scale (HAM-D) (Hamilton et al, 1960). Euthymia will be defined by a score of HAM-D <= 8 points.	Baseline to follow-up (12 months)

Collaborators and Investigators

• Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: September 30, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Mood Disorder; Bipolar Disorder; Cognitive Remediation; Cognitive Enhancement; Psychosocial Functioning; Functional Remediation; Cognitive Dysfunctions; Psychosocial interventions
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Bipolar and Related Disorders; Disease; Bipolar Disorder
• Other Study ID Numbers: NP 3976

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No