Clinical trial NCT05565170: Digitally Supported Lifestyle Programme to Promote Brain Health Among Older Adults
Official title: Digitally Supported Lifestyle Programme to Promote Brain Health Among Older Adults - the LETHE Pilot Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Cognitive Impairment
Cognitive Decline
Dementia
Keywords: Prevention
Risk reduction
Brain health
Lifestyle intervention
Digital intervention
eHealth
Telemedicine
Lead sponsor: Finnish Institute for Health and Welfare
Sponsor class: OTHER_GOV
Collaborators: name: Medical University of Vienna
name: Karolinska Institutet
name: University Of Perugia
name: FH Joanneum Gesellschaft mbH
name: Foundation for Research and Technology - Hellas (FORTH)
name: Infotrend Innovations Co Ltd
name: Innovation To Grow
name: Kaasa solution GmbH
name: Lisbon Council
name: Maastricht University
name: Combinostics Oy
name: Alzheimer Europe
name: Extra Red s.r.l.
name: Stichting EGI
First posted: 2022-10-04
Enrollment: 156
Sex: ALL
Minimum age (years): 60
Maximum age (years): 77
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are randomised 1:1 to two parallel arms:

* structured ICT-assisted multimodal lifestyle intervention (intervention group)
* self-guided multimodal lifestyle intervention (control group)
Primary purpose: PREVENTION

Brief summary: Previous research has shown that a healthy lifestyle, including a balanced diet, physical and social activity, and management of vascular risk factors can support both cardiovascular and brain health. In a landmark Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a multimodal lifestyle programme had clear benefits on older adults' cognition, functioning, and quality of life. The LETHE study utilises novel technologies and digital tools to deliver an optimised and more personalised FINGER-type multimodal lifestyle intervention.

A total of 160 digitally skilled older adults (age 60-77) with risk factors for dementia but without substantial cognitive impairment will be recruited in Austria, Finland, Italy, and Sweden. Participants will be randomly assigned in a 1:1 ratio to the structured ICT-assisted multimodal lifestyle program (intervention group) or a self-guided lifestyle program (control group). Duration of the study and the intervention is 24 months. The multimodal lifestyle program covers the following domains: physical activity, nutrition, cognitive activity, vascular risk management, social interaction, sleep, and relaxation. The structured intervention program follows a hybrid model where regular in-person, individual and group-based intervention activities led by professionals are supported with activities in the LETHE mobile phone application. The self-guided (control) group receives relevant health advice and is recommended and encouraged to independently implement healthy lifestyle changes that are suitable and fit in with their daily routine. Control group will have access to a simplified version of the LETHE app without any structured, scheduled activities or personalized content.

The primary objective of the LETHE trial is to test the feasibility of a digitally supported multimodal lifestyle program (i.e., retention rate, adherence to intervention), and assess change in dementia risk based on validated risk scores (CAIDE, LIBRA). Other objectives include testing the intervention effects on lifestyle and risk factors, cognition, function, health-related quality of life, health literacy, physical functioning, and dementia-related biomarkers. To this aim, a range of personal, lifestyle, and health-related data will be collected both actively and passively with the help of digital devices. Attitudes towards digital tools and experiences of trial participation will also be explored.

Detailed description: The LETHE pilot trial is a 24-month multicentre parallel-group randomised controlled trial conducted in Finland (Finnish Institute for Health and Welfare, THL), Austria (Medical University of Vienna, MUW), Sweden (Karolinska Institute, KI), and Italy (University of Perugia, UPG). LETHE is an academic-led trial (funded by EU Commission) where all four clinical centers are jointly and equally responsible for the planning and conduct of the trial.

The recruitment goal is 160 participants (40 per country). Participants will be recruited e.g., through public announcements or advertisements (newspaper, social media) and at the local study centres. Interested individuals will first be pre-screened to check the key inclusion criteria related to e.g., age, digital skills and readiness, and risk factor profile (CAIDE dementia risk score). Persons who appear to meet the inclusion criteria (and no reasons for exclusion have arisen) are then invited for the actual screening assessment visit (organised remotely or in-person) where the eligibility criteria are checked in detail (including cognition). Exclusion criteria are assessed by a physician (for those who meet the inclusion criteria). Eligible individuals are invited to the baseline visit at the study centre. After completing all baseline assessments, participants are randomised in 1:1 ratio to the intervention group (structured ICT-assisted multimodal lifestyle intervention) and control group (self-guided multimodal lifestyle intervention). Randomisation will be balanced across sites.

At the beginning of the study, all participants receive an Android smartphone (unless they have already a compatible phone which they prefer to use), first with a simplified version of the LETHE App installed where participants can complete a set of outcome assessment questionnaires (e.g., lifestyle-related). After randomisation, a visit is booked to hand out the Fitbit smartwatch (different versions for the intervention and control groups) and install the full study version of the App (also different for the different groups). The App and the smartwatch are used for both active and passive data collection throughout the trial, and to support the intervention delivery. The intervention group will be offered a structured and tailored multimodal lifestyle programme (based on the FINGER model) including regular in-person (face-to-face and remote) counselling and sessions led by professionals, as well as independent digital activities in the LETHE App. Sessions and activities are related to the following intervention components: physical activity, nutrition, cognitive activity, vascular risk management and monitoring, social interaction, sleep, and relaxation/stress management. Recommendations and plans are tailored. The LETHE App, which has been designed by the LETHE consortium for this project, has features such as e.g., a cognitive training program, on-demand exercise videos, calendar to schedule activities, advice and educational material, group chat, and possibility to set and monitor goals and self-monitor risk factors such as e.g., blood pressure. Participants in the self-guided group are instructed to build their own lifestyle programme based on general health and lifestyle recommendations that they will receive at the main study visits. They will also have access to a simplified version of the LETHE App with static educational content about healthy lifestyle, but without any structured and scheduled activities, interactive features, or personalised content.

After baseline, all participants are invited to the study centre for three main study visits to collect outcome information, at month 6, 12, and 24. The outcome assessors are blinded to the group allocation and participants are not actively told to which group they were assigned. Data collection through the digital devices takes place continuously. The primary objective of the trial is to assess the feasibility of the digitally supported multimodal lifestyle intervention programme, i.e., assess retention rate (what proportion of participants completes the 24-month intervention period) and adherence to the intervention and engagement with the digital tools. Furthermore, changes in validated dementia risk scores (CAIDE, LIBRA) are assessed. Other objectives include testing the intervention effects on lifestyle and different risk factors of cognitive decline and dementia, cognitive performance, physical functioning, health-related quality of life, health literacy, and dementia-related fluid and imaging biomarkers. Participants' experiences of study participation and views on e.g., the usability and acceptability of the digital tools will also be explored (through interviews/focus groups).

Eligibility criteria: Inclusion Criteria:

* Age 60-77 years
* Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) Risk Score ≥ 6 points
* Cognitive performance at the mean level or slightly lower than expected for age, assessed with Mini-Mental State Examination (MMSE) and the Consortium to Establish a registry for Alzheimer's Disease (CERAD) verbal learning test (word list learning/recall)
* Proficiency in the local language (German, Italian, Finnish or Swedish)
* Ability and willingness to use an Android smartphone, access to and ability to use the internet (digital readiness)
* Existing compatible smartphone (Android) or willingness to use a new Android smartphone provided from the study

Exclusion Criteria:

* Dementia or substantial cognitive impairment (e.g., memory clinic referral needed as judged by the study physician)
* Current or past use of medications for Alzheimer's disease or related diseases (e.g., cholinesterase inhibitors, memantine)
* Diminished decision-making capacity, not capable of consenting or completing study assessments, based on clinical judgement
* Other significant neurologic disease, including but not limited to Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities
* Any condition affecting safe engagement in the intervention, e.g., malignant disease, major depression, symptomatic cardiovascular disease, revascularisation within 1 year previously
* Severe loss of vision, hearing, or communicative ability; conditions preventing cooperation as judged by the study physician
* Concomitant participation in an interventional trial (unless this will not interfere with the LETHE trial based on study staff's judgement)

Primary outcomes:
measure: Feasibility: retention rate
timeFrame: 24 months
measure: Feasibility: adherence to the structured multimodal lifestyle intervention
timeFrame: Continuously measured during 24 months
measure: Change in dementia risk scores (LIBRA and CAIDE), units on a scale
timeFrame: Baseline, 12 months, 24 months
Secondary outcomes:
measure: Change in healthy lifestyle, unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Change in cognition: composite z-score based on an extended Neuropsychological Test Battery (NTB), unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Change in stress-related symptoms (Perceived Stress Scale, PSS-14), unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Change in sleep problems (Insomnia Severity Index, ISI), unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Change in health-related quality of life (RAND-36), unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Change in health literacy (short version of the European Health Literacy Survey Questionnaire, HLS-EU-Q16), unit on a scale.
timeFrame: Baseline, 24 months
Other outcomes:
measure: Exploratory: Change in physical activity - self-reported, unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Exploratory: Change in physical activity - objective, based on Fitbit smartwatch
timeFrame: Continuously for 24 months
measure: Exploratory: Change in dietary intake, unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Exploratory: Change in individual cognitive domains, unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Exploratory: Change in cognition based on the digital assessment of cognitive performance (cCOG), unit on a scale
timeFrame: 1 month, 13 months, 25 months (approx. 1 month after each main study visit and NTB assessment)
measure: Exploratory: Change in global cognition/function: Clinical Dementia Rating Sum of Boxes (CDR-SB), unit on a scale
timeFrame: Baseline, 24 months
measure: Exploratory: Change in functioning level: Instrumental Activities of Daily Living (IADL), unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Exploratory: Change in blood pressure, mmHg
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Exploratory: Change in Body Mass Index (BMI), kg/m²
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Exploratory: Change in waist circumference, cm
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Exploratory: Change in concentration of blood lipids - total cholesterol, mmol/l
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Exploratory: Change in concentration of blood lipids - HDL, mmol/l
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Exploratory: Change in concentration of blood lipids - LDL, mmol/l
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Exploratory: Change in concentration of blood triglycerides, mmol/l
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Exploratory: Change in concentration of plasma glucose, mmol/l
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Exploratory: Change in concentration of glycated haemoglobin (HbA1c), %
timeFrame: Baseline, 6 months, 12 months, 24 months
measure: Exploratory: Change in heart rate, bpm
timeFrame: Continuously for 24 months
measure: Exploratory: Change in amount of social interaction (based on the total count of nearby Bluetooth devices)
timeFrame: Continuously for 24 months
measure: Exploratory: Change in physical functioning: timed 10-meter dual-task test, gait speed in m/s and gait cost
timeFrame: Baseline, 24 months
measure: Exploratory: Change in physical functioning: Short Physical Performance Battery (SPPB), unit on a scale
timeFrame: Baseline, 24 months
measure: Exploratory: Change in physical functioning: hand grip strength, kg
timeFrame: Baseline, 24 months
measure: Exploratory: Change in depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D), unit on a scale
timeFrame: Baseline, 12 months, 24 months
measure: Exploratory: Change in sleep parameters based on Fitbit smartwatch data, unit on a scale
timeFrame: Continuously for 24 months
measure: Exploratory: Attitudes towards new technologies and novel digital solutions (System Usability Scale, SUS), unit on a scale
timeFrame: 1 month, 6 months, 24 months
measure: Exploratory: Change in serum concentration of neurofilament light chain, NFL, pg/ml
timeFrame: Baseline, 24 months
measure: Exploratory: Change in serum concentration of pTau-181, ng/uL
timeFrame: Baseline, 24 months
measure: Exploratory: Change in brain imaging markers: volumetry of brain segments based on magnetic resonance imaging, MRI
timeFrame: Baseline, 24 months
measure: Exploratory: Change in brain imaging markers: white matter lesions
timeFrame: Baseline, 24 months
measure: Exploratory: Change in brain imaging markers: brain atrophy and vascular load, based on widely used rating scales, units on a scale
timeFrame: Baseline, 24 months
measure: Exploratory: Participant experiences of the trial and the usability, acceptability, and feasibility of the digital intervention tools
timeFrame: 24 months
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Helsinki
country: Finland
facility: Finnish Institute for Health and Welfare
city: Perugia
country: Italy
facility: University of Perugia
city: Stockholm
country: Sweden
facility: Karolinska Institutet
Study officials:
affiliation: Finnish Institute for Health and Welfare
name: Tiia Ngandu, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Vienna
name: Elisabeth Stögmann, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Francesca Mangialasche, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Of Perugia
name: Patrizia Mecocci, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: