Clinical trial NCT05387057: Effectiveness of a Novel Exergame-Based Training Concept for Older Adults With Mild Neurocognitive Disorder
Official title: Effectiveness of an Individualized Exergame-based Motor-Cognitive Training Concept Targeted to Improve Cognitive Functioning in Older Adults With Mild Neurocognitive Disorder - A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mild Neurocognitive Disorder
Keywords: Exergames
Mild Neurocognitive Disorder
Cognition
Neuroscience
Exercise
Training
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
First posted: 2022-05-24
Enrollment: 41
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Allocation ratio = 1 (Intervention) : 1 (Control) stratified by gender and per institute (study site)
Primary purpose: PREVENTION

Brief summary: BACKGROUND:

Simultaneous motor-cognitive training interventions are considered promising to prevent the decline in cognitive functioning in older adults with mild neurocognitive disorder (mNCD) and can be highly motivating when applied in form of exergames.

OBJECTIVES:

This study systematically explores the effectiveness of a newly developed exergame-based motor-cognitive training concept (called 'Brain-IT') targeted to improve cognitive functioning in older adults with mNCD.

METHODS:

A two-arm, parallel-group, single-blinded (i.e. outcome evaluator of pre- and post-measurements blinded to group allocation) randomized controlled trial with an allocation ration of 1 : 1 (i.e. intervention : control) including 34 - 40 older adults with mNCD will be conducted between May 2022 and December 2023. The control group will proceed with usual care as provided by the (memory) clinics where the patients are recruited while the intervention group will perform a twelve-week training intervention according to the newly developed 'Brain-IT' exergame-based training concept in addition to usual care. As a primary outcome, global cognitive functioning will be assessed using the Quick Mild Cognitive Impairment Screen (Qmci). As secondary outcomes, domain-specific cognitive functioning, brain structure and function, spatiotemporal parameters of gait, instrumental activities of daily living, psychosocial factors (e.g. quality of life, and levels of depression, anxiety, stress), and cardiac vagal modulation (heart rate variability at rest) will be assessed. Both, the pre- and the post-measurements will take place within two weeks prior to starting or after completing the intervention.

Detailed description: BACKGROUND:

Simultaneous motor-cognitive training interventions are considered promising to prevent the decline in cognitive functioning in older adults with mild neurocognitive disorder (mNCD) and can be highly motivating when applied in form of exergames. To ameliorate the effectiveness of exergaming, the neurobiological mechanisms as well as the most effective components for exergame interventions remain to be established. Besides establishing the most effective components \[i.e., qualitative (e.g., type and content of training) and quantitative (e.g., frequency, intensity/complexity, session duration, intervention dose and adaptation over time) exercise and training variables\] of exergames for cognition, it is crucial to also account for the users' perspective when designing and developing novel exergames or training concepts.

On this basis, a novel exergame-based training concept (called the 'Brain-IT' exergame-based training concept) was developed specifically for older adults with mNCD with the aim to halt and/or reduce cognitive decline and improve quality of life in older adults with mNCD. This exergame-based training concept has been developed on basis of a structured, iterative, and evidence-based approach based on a theoretical framework - The 'Multidisciplinary Iterative Design of Exergames (MIDE): A Framework for Supporting the Design, Development, and Evaluation of Exergames for Health'. The 'Brain-IT' exergame-based training concept represents a guideline for applying exergame-based motor-cognitive training by standardizing the training characteristics (e.g. training frequency, duration), as well as the structure and content of the training, whereas the exergame device and the games used within each of the defined neurocognitive domains can be replaced at will by alternative exergames. In this study, our training concept is implemented using the 'Senso (Flex)' (Dividat AG, Schindellegi, Switzerland), because this training device is already widely used for motor-cognitive training within geriatric populations, physiotherapies or in rehabilitation in Switzerland and was found to be suitable to implement our training concept. A step-by-step explanation of our methodological approach including the basis for the decision for the design of the exergame-based training concept as well as the complete 'Brain-IT' exergame-based training concept with sufficient details to allow full replication has been published as a methodological paper (doi: 10.3389/fnagi.2021.734012). The 'Brain-IT' exergame-based training concept has already been tested in a pilot randomized controlled trial and has shown good results in feasibility (i.e. recruitment, adherence, compliance, attrition), usability (i.e. system usability), and acceptance (i.e. enjoyment, training motivation and perceived usefulness) (unpublished work; NCT04996654). Based on the findings of this study, some minor modifications were incorporated to optimize the training concept so that it can be applied in a larger sample of patients to be evaluated on its effectiveness to halt and/or reduce cognitive decline and improve quality of life in older adults with mNCD.

OBJECTIVES \& HYPOTHESES:

This study explores the effectiveness of the 'Brain-IT' training to improve global cognitive func-tioning in older adults with mNCD. With this, we aim to get a sufficiently precise estimate of the treatment effect to minimize the sample needed for a future full-scale RCT.

Null Hypothesis (H0): In older adults with mNCD, the addition of the 'Brain-IT' training to usual care has no significant effect on global cognitive functioning compared to usual care.

Alternative Hypothesis (HA): In older adults with mNCD, the addition of the 'Brain-IT' training to usual care results in differing effects on global cognitive functioning compared to usual care.

As secondary objectives, the effects of the 'Brain-IT' training on: (1) domain-specific cognitive functioning (i.e. learning and memory, complex attention, executive function, and visuospatial skills), (2) brain structure and function, (3) spatiotemporal parameters of gait, (4) IADL and (5) psychosocial factors (i.e. QoL, and levels of depression, anxiety, stress), and (6) cardiac vagal modulation (i.e. resting vagally-mediated heart rate variability (vm-HRV)) in older adults with mNCD as compared to usual care will be explored. Brain structure and function will be evaluated to explore possible underlying neural changes of the training in relation to adaptations in cognitive performance. For the remaining outcomes, the following hypotheses were formulated:

Null Hypothesis (H0): In older adults with mNCD, the addition of the 'Brain-IT' training to usual care has no significant effect on (1) domain-specific cognitive functioning, (3) spatiotemporal parameters of gait, (4) IADL and (5) psychosocial factors (i.e. QoL, and levels of depression, anxiety, stress), and (6) cardiac vagal modulation (resting vm-HRV) com-pared to usual care.

Alternative Hypothesis (HA): In older adults with mNCD, the addition the 'Brain-IT' training to usual care results in differing effects on (1) domain-specific cogni-tive functioning, (3) spatiotemporal parameters of gait, (4) IADL, (5) psychosocial factors (i.e. QoL, and levels of depression, anxiety, stress), and (6) cardiac vagal modulation (resting vm-HRV) com-pared to usual care.

METHODS:

A two-arm, parallel-group, single-blinded (i.e. outcome evaluator of pre- and post-measurements blinded to group allocation) randomized controlled trial with an allocation ration of 1 : 1 (i.e. intervention : control) including 34 - 40 older adults with mNCD will be conducted between May 2022 and December 2023.

After recruitment, interested subjects will be screened on eligibility between May 2022 and September 2023. All potential subjects will be fully informed about the study procedures by providing verbal explanations and an information sheet. Expected effects, benefits and risks of the study will be explained by the investigators, who will also be available to answer open questions and clarify uncertain-ties of participants. It will further be verified, that withdrawal is permitted at any time during the study without having to give a reason. After sufficient time for considerations (i.e. at least 24 h after handing out the study information sheet, but on average around two weeks), suitable patients willing to take part in the study will provide written informed consent in a second in-person meeting with the study team at the interested persons' home or at one of the study centres, depending on their preferences. If eligible patients decline to participate in the study, all data researched by their doctors or therapists and submitted to the study team will be permanently deleted. After providing written informed consent, the participants will be fully screened on eligibility, and the third study appointment (pre-measurements) will be scheduled. For participants recruited in the area of Zurich, the pre-measurements will take place at ETH Hönggerberg (Robert-Gnehm-Platz 1, CH-8093 Zurich). For participants recruited in the area of St.Gallen, the pre-measurements will take place at Eastern Switzerland University of Applied Sciences (Vadianstrasse 29, CH-9000 St.Gallen). The measurements will take approximately 60 - 90 min. For all participants who have no contraindications to MRI, an additional appointment to conduct the MRI scan will be scheduled. The MRI scan will take place at University Hospital Zurich (Rämistrasse 100, CH-8006 Zurich) and will take approximately one hour (including preparation). After completing the pre-measurements, participants will be randomly allocated to the intervention group (i.e. 'exergame group') or control group (i.e. 'usual care'). All participants will be instructed about their respective intervention procedures. For participants in the exergame group, the device will be installed at their homes, they will get a safety instruction and will be familiarized with the exergame training system 'Senso Flex', and the study intervention will be started according to the newly developed 'Brain-IT' exergame-based training concept (see section 'Intervention'). After completing the twelve-week intervention period, post-measurements (POST) will be performed for both groups. Both, the pre- and the post-measurements will take place and within two weeks prior to starting or after completing the intervention. No compensation will be granted to the participants, but detailed feedback on individual performance as well as the study outcomes in general will be provided at the end of the trial if desired.

Eligibility criteria: INCLUSION CRITERIA:

Participants fulfilling all of the following inclusion criteria are eligible for the study:

* (1 = mNCD) clinical diagnosis of 'Mild Neurocognitive Disorder' according to the International Classification of Diseases 11th Revision (ICD-XI) or the Diagnostic and statistical manual of mental disorders (DSM-5®)) OR (2 = sMCI) patients screened for mild cognitive impairment (sMCI) according to the following criteria: (a) informant (i.e. healthcare professionals)-based suspicion of MCI confirmed by (b) an objective screening of MCI based on the German Version of the Quick Mild Cognitive Impairment Screen with (b1) a recommended cut-off score for cognitive impairment (MCI or dementia) of \< 62/100 (doi: 10.3233/JAD-161204), while (b2) not falling below the cut-off score for dementia (i.e. \< 45/100 (doi: 10.3233/JAD-161204)).
* German speaking
* able to stand at least for 10 min without assistance

EXCLUSION CRITERIA:

The presence of any of the following exclusion criteria will lead to exclusion of the participants:

* mobility impairments (i.e. gait, balance) that prevent experiment participation
* presence of additional, clinically relevant (i.e. acute and/or symptomatic) neurological disorders (i.e. epilepsy, stroke, multiple sclerosis, Parkinson's disease, brain tumors, or traumatic disorders of the nervous system)
* presence of any other unstable or uncontrolled diseases

Additional exclusion criteria will comprise of Covid-19 specific exclusion criteria (according to the Federal Office of Public Health). In case of Covid-19 specific exclusion criteria, participation in the study will only be allowed in case the treating physician provided written informed consent to allow participation in this study despite the presence of Covid-19 specific exclusion criteria. These Covid-19 specific exclusion criteria will include:

* high blood pressure (self-reported; systolic ≥ 140 mmHg and/or Diastolic ≥ 90 mmHg)
* Chronic respiratory condition
* uncontrolled type 2 Diabetes
* Condition or therapy that weakens the immune system
* unstable Cardiovascular Disease
* Cancer (present and/or under treatment)
* Serious obesity (BMI ≥ 40 kg/m2)

Primary outcomes:
measure: Changes in Global Cognition
timeFrame: Both, the pre- and the post-measurements of the primary outcome measurement will take place within two weeks prior to starting or after completing the intervention.
Secondary outcomes:
measure: Changes in Learning and Memory - Part 1
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Learning and Memory - Part 2
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Complex Attention - Part 1
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Complex Attention - Part 2
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Executive Function - Part 1
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Executive Function - Part 2
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Executive Function - Part 3
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Visuospatial Skills
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Brain Structure and Function - Part 1 (Grey Matter Volumes)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Brain Structure and Function - Part 2 (White Matter Volumes)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Brain Structure and Function - Part 3 (Mean diffusivity)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Brain Structure and Function - Part 4 (Fractional Anisotropy)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Brain Structure and Function - Part 5 (Functional Connectivity Maps at rest)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Brain Structure and Function - Part 6 (Functional Connectivity Maps during an episodic memory-task)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Spatiotemporal Gait Parameters - Part 1 (single-task gait speed at preferred walking speed)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Spatiotemporal Gait Parameters - Part 2 (stride duration)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Spatiotemporal Gait Parameters - Part 3 (stride length)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Spatiotemporal Gait Parameters - Part 4 (stance phase duration)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Spatiotemporal Gait Parameters - Part 5 (swing time)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Spatiotemporal Gait Parameters - Part 6 (single support time)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Spatiotemporal Gait Parameters - Part 6 (double support time)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Instrumental Activities of Daily Living (IADL)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Psychosocial Factors - Part 1 (Quality of Life)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in Psychosocial Factors - Part 2 (Symptoms of Depression)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
measure: Changes in vagally-mediated Heart Rate Variability (HRV)
timeFrame: Both, the pre- and the post-measurements of all secondary outcome measurements will take place within two weeks prior to starting or after completing the intervention.
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: ETH Zurich
Study officials:
affiliation: ETH Zurich
name: Eling D de Bruin, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Manser P, de Bruin ED. Making the Best Out of IT: Design and Development of Exergames for Older Adults With Mild Neurocognitive Disorder - A Methodological Paper. Front Aging Neurosci. 2021 Dec 9;13:734012. doi: 10.3389/fnagi.2021.734012. eCollection 2021.
citation: Manser P, de Bruin ED. "Brain-IT": Exergame training with biofeedback breathing in neurocognitive disorders. Alzheimers Dement. 2024 Jul;20(7):4747-4764. doi: 10.1002/alz.13913. Epub 2024 May 29.