Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02766361 |
| Other study ID # |
CNPQ 458144/2014-2 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 2016 |
| Est. completion date |
December 2023 |
Study information
| Verified date |
May 2022 |
| Source |
University of Sao Paulo |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The study consists of a clinical trial comparing a new structured group intervention,
denominated "Cognitive-Behavioral Rehabilitation", to treatment as usual (TAU) for bipolar
patients. The new approach is a combination of cognitive behavioral strategies and cognitive
rehabilitation exercises, consisting of twelve weekly group sessions of 90 minutes each. To
be included in the study, patients must be diagnosed with bipolar disorder, type I or II, be
18 to 55 years old, in full or partial remission and have an IQ of at least 80. A
comprehensive neuropsychological battery, followed by mood, social functioning and quality of
life assessments will occur in three moments: pre and post-intervention and after 12 months.
Description:
Methods/Design The study compares Cognitive Behavioral Rehabilitation with Treatment as Usual
(TAU), the latter being the commonly offered pharmacological treatment to bipolar patients.
The psychological intervention will consist of twelve weekly group sessions, lasting 90
minutes each, and including 8 to 10 individuals. Subjects will be randomly assigned to one of
the two arms, and submitted to a 12-month follow-up. During the entire study, all patients
will be medicated accordingly to their clinical needs, and all changes in medication will be
recorded as a secondary outcome , following the Necessary Clinical Adjustment (NCA)
instrument. The NCA records medication adjustments implemented to reduce symptoms, improve
response and functioning, or handle unbearable side effects.
Participants In order to be included, patients must be between 18 to 55 years old, literate,
present an IQ score higher than 80 and have been diagnosed with bipolar I or II accordingly
to DSM-V criteria (APA, 2014). Excluding conditions are: presence of substance or alcohol
abuse in the last 6 months, current suicide risk, organic mental disorders or scores higher
than 12, in the Montgomery-Asberg Depression Rating Scale (MADRS) or the Young Mania Rating
Scale (YMRS) at the beginning of the interventions.
Recruiting will take place at an outpatient service provided by the Bipolar Disorder Research
Program (PROMAN) at the University of São Paulo Medical School, Brazil. Patients will receive
invitations individually, and sign an informed consent.
Procedure and Outcomes Once included, patients will complete the Portuguese versions of the
following self-report questionnaires: the abbreviated instrument of quality of life
(WHOQOL-bref), the Barratt Impulsiveness Scale 11 (BIS 11), the Social Skills Inventory (IHS)
and the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) . Patients will
also complete the Functioning Assessment Short Test (FAST) and a brief questionnaire about
bipolar disorder.
A brief neuropsychological battery will be conducted, which includes the Wechsler Abbreviated
Scale of Intelligence (WASI) (Wechsler, 1999), and following subtests from the Cambridge
Neuropsychological Test Automated Battery (CANTAB): Motor Screening Task (MOT); Rapid Visual
Information Processing (RVP); Reaction Time (RTI); Spatial Span (SSP); Spatial Working Memory
(SWM); One Touch Stockings of Cambridge (OTS); Pattern Recognition Memory (PRM); Delayed
Matching to Sample (DMS); Attention Switching Task (AST); Emotion Recognition Task (ERT).
Subjects will also complete the initial assessment and mood module of the Structured Clinical
Interview for DSM-5 (SCID-5) (APA, 2014) post-intervention at week 12, and 6 and 12 months
thereafter.
Hypothesis
The study hypothesizes that Cognitive Behavioral Rehabilitation, in comparison to TAU, will:
I. Decrease the recurrence rates of new episodes; our primary outcome measure. II. Improve
attention, mental flexibility, working memory and emotional recognition; our secondary
outcome.
In an exploratory analysis we will also assess whether Cognitive Behavioral Rehabilitation
may:
A. Enhances functional, social skills and quality of life scores; B. Increases sleep quality
and knowledge about the disorder; and C., Reduces impulsivity
Interventions
Treatment as Usual (TAU) The control group from this study will receive standard out-patient
treatment offered in our clinic, which involves psychopharmacological mood stabilization and
regular contacts with mental health nurses. The number and amount of pharmacological
treatment will follow the physician decision, respecting individual demands. All
pharmacological treatment will be monitored and recorded in accordance to the Litmus study
(Nierenberg et al. 2009).
Cognitive Behavioral Rehabilitation
We developed a 12-session intervention combining previous experience in cognitive behavior
therapy for bipolar patients with several elements of cognitive remediation. The first step
was to identify behaviors that have an important role in patients´ autonomy, followed by
determining which cognitive domains are involved. The core objective was to promote the
generalization of the learnt behaviors in the daily routine. Described below is the
arrangement of each session, divided in three major Modules:
In the first Module comprises four sessions that attempt to improve attention and memory,
considering the necessity to retain the information discussed throughout the sessions. There
are two target behaviors involved: adherence to pharmacological treatment and mood
monitoring. The cognitive remediation exercises seek to enhance verbal and visual memories,
while secondarily enhancing attention with the paper material included in the manual. In the
first session, group members and psychotherapists introduce themselves, followed by a
discussion regarding the manual, individual´s expectations and the importance of attendance.
The second session explores the concept of attention, and its importance as a door to further
cognitive functions; the group also learns exercises aimed at training attention and memory.
The third session focuses on medication adherence and its relation to attention. The core of
the third session is the organization of the patient´s environment, which is frequently
chaotic; a discussion about cues is encouraged at the end of the session. The fourth session
starts by introducing mood graphics to patients and the importance of the early identifying
of mood episodes. At the end of the first module, patients are stimulated to cook as method
of reinforcing what they have learned while enhancing their autonomy.
The second module targets social cognition and communication. The fifth session familiarizes
the patients with the concept of automatic thoughts (Rush and Beck, 1978), and a guide to
identify its presence. Cognitive distortions are discussed along with examples provided by
the subjects´ own experiences. The sixth session begins returning to the initial theme by
habituating patients to the automatic thought record (Beck, 1997), patients are stimulated to
restructure their own thoughts during experiences identified in previous sessions. Mental
flexibility and empathy are introduced and discussed. The seventh session acquaint patients
to assertive communication and emotion recognition by teaching role-playing exercises and the
importance of positive assertiveness. The eighth session follows the same agenda as the
seventh.
The last module of Cognitive Behavioral Rehabilitation aims at problem solving strategies and
relapse prevention. The ninth session begins with the identification of personal problems,
mainly by distinguishing it from preoccupations; the topic is important because patients
often incorporate their problems to expectations and desires, generating an urge to abandon
them, the session ends by emphasizing the importance of mental flexibility in generating as
many responses as possible to each identified problem. In the tenth session, patients learn
solving-problem techniques in a systematic setting. The eleventh session devotes to review
information and clarify possible doubts from the patients; patients are also encouraged to
debate the importance of regular routines and regular sleep, which can be adjusted using
sleep hygiene techniques. A progressive muscle relaxation ends the session. Finally, the last
session´s target is to avoid future mood relapses, it by returning to the personal goals
defined in session one and prompting patients to develop a prevention plan. The acronym
H.U.M.O.R. resumes the core points of the post-intervention maintenance program: 1) Habituate
to a regular routine; 2) Use what you have learnt; 3) Monitor your mood; 4) Observe arising
problems and deal effectively with it; and 5) Respond to automatic thoughts. All patients in
the cognitive behavioral rehabilitation group will also receive TAU.
Statistical Analysis Sample Size The sample size calculation was based on the proportion of
patients that remain episode-free after 12 months following a group intervention. Previous
studies utilizing TAU exhibited a decrease of bipolar relapses in 30% of patients after a
one-year follow-up. The present study anticipates a 55% success rate in prevention of mood
relapses, during the same period, in patients assigned to the Cognitive Behavioral
Rehabilitation. Thus, considering an 80% power to obtain a 5% significance, an estimated
sample of 28 individuals per group, 56 in total, should be sufficient to achieve significant
results. A previous study conducted by the same research team measured a drop-out rate of 10%
in a one year follow-up, for this latter reason, the study will consist of 60 participants.
Baseline and Follow up Data. In order to measure the effects of the interventions, the study
will employ the following statistical tests: 1) Qui-squared and Mann-Whitney to test
homogeneity between the groups at the beginning of the interventions; 2) Student t test or
Mann-Whitney to investigate the effects of such interventions, pre and post treatment,
depending on the distribution of the data; 3) An analysis of variance, with and without
adjustment for mood symptoms scores, IQ and BD duration, for comparison between groups; and
4) The Kaplan-Meyer survival method with log rank test for statistical analysis, to
investigate the survival data between groups, which measures in weeks, the time to the first
episode as an event.
