Clinical trial NCT05133869: Brain Outcome After Cardiac Arrest - Intervention
Official title: BROCA-intervention Brain Outcome After Cardiac Arrest- Single Case Experimental Design Intervention Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Arrest, Out-Of-Hospital
Cognitive Impairment
Keywords: Cardiac Arrest
Cognitive Rehabilitation
Neuroplasticity
Cognitive training
Lead sponsor: Maastricht University
Sponsor class: OTHER
Collaborators: name: Rijnstate Hospital
name: Adelante, Centre of Expertise in Rehabilitation and Audiology
name: Maastricht University Medical Center
First posted: 2021-11-24
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a randomized multiple baseline single case experimental design (SCED) intervention study.
Primary purpose: TREATMENT

Brief summary: People who suffered a cardiac arrest are often have cognitive impairments. In this study the investigators test the effectiveness of an intervention, combining direct training and metacognitive training, in a single case experimental design (SCED).

Detailed description: SUMMARY

Rationale: The survival rate of patients after cardiac arrest and resuscitation has increased considerably. A common consequence of cardiac arrest is ischemic-hypoxic brain damage leading to cognitive impairment. Currently, there is a lack of knowledge regarding effectiveness of treatments to improve outcomes of patients with cognitive impairment after a cardiac arrest.

Objective: The primary objective is to test effectiveness of cognitive rehabilitation therapy to improve functioning on problematic well-defined personalized behaviour that is caused by an objective cognitive impairments after OHCA. Secondary objectives are to test the generalisation of the effect of the intervention towards other aspects of daily living, to estimate the effect of the intervention on objective and subjective measures of cognitive functioning, participation in society, and quality of life, and to detect evidence of neuroplasticity in MRI data.

Study design: This is a randomized multiple baseline single case experimental design (SCED) intervention study.

Study population: The four to six participants included in this study will be patients surviving a cardiac arrest and cardiopulmonary resuscitation with remaining cognitive impairments at least 3 months after the cardiac arrest, who are motivated to adhere to the training program tested in this study.

Intervention: The intervention will consist of a combination of direct training of the impaired cognitive function(s) and metacognitive strategy training for 42 days (6 weeks). Direct training will be done with the computer program Rehacom to train the impaired cognitive domains, for 20 minutes 5 times a week. Metacognitive strategy training will be given on a weekly or biweekly basis (6-10 sessions) by a trained therapist as current care.

Main study parameters/endpoints: The primary outcome measure is the score on a Visual Analogue Scale (VAS) of the severity of the main, predefined daily life problem caused by objective cognitive impairment(s) that the participant is dealing with. The primary outcome measure will be collected by an App, through which the patient will receive questions on his / her telephone, daily. Answering will take less than one minute. Secondary outcome measures are daily obtained VAS scores on general and potential other daily life problems, and scores on neuropsychological tests and questionnaires that are obtained four times during the study, and MRI data obtained at two different time-points.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The investigators foresee no relevant additional risk of cognitive rehabilitation therapy and follow up in this study. Daily training and collection of outcomes will be challenging, but feasible, since the investigators will include motivated patients who will mostly judge the careful follow up as pleasant and attentive. MRI scanning is only performed in patients suitable for scanning, no contrasts are used. Potential benefit from participation in this study is follow up and treatment of cognitive impairments may lead to improved functional recovery after cardiac arrest.

Eligibility criteria: Inclusion Criteria:

In order to be eligible to participate in this study, a subject must be mentally competent and meet all of the following criteria:

* Objectified cardiac arrest between 3 months and 2 years before inclusion.
* Age 18 - 75
* Cognitive impairments objectified by a score on the Montreal Cognitive Assessment (MoCA) ≤ 26 or abnormal scores on a neuropsychological assessment caused by low scores (more than 1,5 standard deviation below the mean of the norm group) on memory, attention, and/or executive functioning tasks
* Living independently (with minor help)
* Experiencing difficulties with more complex daily tasks (e.g. doing groceries, following conversations, etc.)
* Motivated to improve cognitive functioning and to participate in the study
* Proficient in Dutch to understand instructions, follow the training program and fill in the questionnaires
* Patients with a treatment indication for cognitive rehabilitation (as decided by a psychiatrist)
* Written informed consent

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

* Neurodegenerative disorder, or another brain disease known to impact cognition, such as stroke or dementia
* Substance abuse impacting cognition
* Psychiatric disorder in need of treatment
* Uncorrected visual or auditory deficiencies
* Not in possession of a computer or lack of computer skills
* Severe amnesia or aphasia
* Illiteracy
* In case of MRI contra-indications, such as an ICD or metallic implants, patients will be excluded from the MRI sub-study. The full list of contraindications can be found in the article of Ghadimi and Sapra (2020).

Primary outcomes:
measure: Change in main daily problem
timeFrame: 85 measurements in 150 days
Secondary outcomes:
measure: Change in other daily problems
timeFrame: 85 measurements in 150 days
measure: Change in general functioning
timeFrame: 85 measurements in 150 days
Other outcomes:
measure: Change in neuropsychological assessment score: Memory, Auditory Verbal Learning Test
timeFrame: < day 1 (before baseline), after baseline (day 15-35 depending on the randomisation), after intervention (day 57 - 77 depending on the randomisation), after follow-up (day 150)
measure: Change in neuropsychological assessment score: Memory, Rivermead Behavioural Memory Test-Stories
timeFrame: < day 1 (before baseline)
measure: Change in neuropsychological assessment score: executive functioning, Digit Span backward
timeFrame: < day 1 (before baseline)
measure: Change in neuropsychological assessment score: executive functioning, Letter Fluency task
timeFrame: < day 1 (before baseline), after baseline (day 15-35 depending on the randomisation), after intervention (day 57 - 77 depending on the randomisation), after follow-up (day 150)
measure: Change in neuropsychological assessment score: attention, digit span forward
timeFrame: < day 1 (before baseline), after baseline (day 15-35 depending on the randomisation), after intervention (day 57 - 77 depending on the randomisation), after follow-up (day 150)
measure: Change in neuropsychological assessment score: attention, Digit Symbol coding task
timeFrame: < day 1 (before baseline)
measure: Change in Questionnaires: cognitive complaints
timeFrame: < day 1 (before baseline), after baseline (day 15-35 depending on the randomisation), after intervention (day 57 - 77 depending on the randomisation), after follow-up (day 150)
measure: Change in Questionnaires: memory complaints
timeFrame: < day 1 (before baseline), after baseline (day 15-35 depending on the randomisation), after intervention (day 57 - 77 depending on the randomisation), after follow-up (day 150)
measure: Change in Questionnaires: participation
timeFrame: < day 1 (before baseline), after baseline (day 15-35 depending on the randomisation), after intervention (day 57 - 77 depending on the randomisation), after follow-up (day 150)
measure: Change in Questionnaires: quality of life
timeFrame: < day 1 (before baseline), after baseline (day 15-35 depending on the randomisation), after intervention (day 57 - 77 depending on the randomisation), after follow-up (day 150)
measure: Change in MRI-data, DTI
timeFrame: before baseline (< day 1), after follow-up (day 150)
measure: Demographics; age
timeFrame: before baseline (< day 1)
measure: Demographics; level of education
timeFrame: before baseline (< day 1)
measure: Demographics; handedness
timeFrame: before baseline (< day 1)
measure: Demographics; Living situation
timeFrame: before baseline (< day 1)
measure: Medical history; time since OHCA
timeFrame: before baseline (< day 1)
measure: Medical history; ROSC
timeFrame: before baseline (< day 1)
measure: Medical history; cause OHCA
timeFrame: before baseline (< day 1)
measure: Medical history; hospitalization length
timeFrame: before baseline (< day 1)
measure: Medical history; implantations
timeFrame: before baseline (< day 1)
measure: Medical history; Comorbidity
timeFrame: before baseline (< day 1)
Locations:
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
state: Gelderland
city: Hoensbroek
country: Netherlands
facility: Adelante
state: Limburg
city: Maastricht
country: Netherlands
facility: Maastricht University
state: Limburg
Study officials:
affiliation: Maastricht University
name: Caroline van Heugten, prof
role: PRINCIPAL_INVESTIGATOR
References: