Digitally Supported Lifestyle Programme to Promote Brain Health Among Older Adults

Dementia Clinical Trial

— LETHE  

Official title:

Digitally Supported Lifestyle Programme to Promote Brain Health Among Older Adults - the LETHE Pilot Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05565170
• Other study ID #: 101017405
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 30, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: June 2023
• Source: Finnish Institute for Health and Welfare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 156
• Est. completion date: March 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 77 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cognitive Decline
• Cognitive Dysfunction
• Cognitive Impairment
• Dementia

Intervention

Behavioral:
• Structured ICT-assisted multimodal lifestyle intervention
The structured lifestyle intervention programme, partly tailored and personalised to individual needs, covers the following domains: physical activity, nutrition, cognitive activity, cardiovascular risk management, social interaction, sleep, and relaxation / stress management. The programme includes regular scheduled in-person sessions (group-based + individual) which are supported with independent digital activities in the LETHE App. The App has features such as e.g., a cognitive training programme, 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.
• Self-guided multimodal lifestyle intervention
Participants are advised to build their own healthy lifestyle programme based on standard healthy lifestyle advice that they will receive at individual consultations with the study physician/nurse as part of the study visits and through the simplified version of the LETHE app. The control group app does not include any structured / scheduled activities or personalised content.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
Finland	Finnish Institute for Health and Welfare	Helsinki
Italy	University of Perugia	Perugia
Sweden	Karolinska Institutet	Stockholm

Sponsors (15)

Lead Sponsor	Collaborator
Finnish Institute for Health and Welfare	Alzheimer Europe, Combinostics Oy, Extra Red s.r.l., FH Joanneum Gesellschaft mbH, Foundation for Research and Technology - Hellas (FORTH), Infotrend Innovations Co Ltd, Innovation To Grow, Kaasa solution GmbH, Karolinska Institutet, Lisbon Council, Maastricht University, Medical University of Vienna, Stichting EGI, University Of Perugia

Countries where clinical trial is conducted

Austria,  Finland,  Italy,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory: Change in physical activity - self-reported, unit on a scale	Self-reported physical exercise in the previous two weeks, using a modified version of the Minnesota Leisure Time Physical Activity Questionnaire, as number of sessions and average duration for each of the activities listed in the questionnaire. Higher levels of physical activity indicate a better outcome.; Self-reported number of sessions of moderate-to-vigorous intensity exercise per week. A higher number of sessions indicates a better outcome.	Baseline, 12 months, 24 months
Other	Exploratory: Change in physical activity - objective, based on Fitbit smartwatch	Objective measurement of physical activity levels, e.g., step count, using the Fitbit smartwatch which is worn continuously throughout the trial. Higher values indicate a better outcome.	Continuously for 24 months
Other	Exploratory: Change in dietary intake, unit on a scale	A brief food frequency questionnaire is used to calculate scores reflecting adherence to a healthy diet (MEDAS score reflecting adherence to Mediterranean-type diet; Healthy Diet Index score developed in Finland in the context of FINGER and type 2 diabetes prevention studies). Higher scores indicate a better outcome.	Baseline, 12 months, 24 months
Other	Exploratory: Change in individual cognitive domains, unit on a scale	Composite z-scores for the: memory; executive function; processing speed domains that are included in the NTB used as a measure for the primary outcome.	Baseline, 12 months, 24 months
Other	Exploratory: Change in cognition based on the digital assessment of cognitive performance (cCOG), unit on a scale	cCOG is a web-based self-administrable cognitive testing tool with three classical cognitive tasks: a modification of word list test, simple reaction task, and TMT. Higher scores and quicker performance indicate a better outcome.	1 month, 13 months, 25 months (approx. 1 month after each main study visit and NTB assessment)
Other	Exploratory: Change in global cognition/function: Clinical Dementia Rating Sum of Boxes (CDR-SB), unit on a scale	CDR and CDR Sum of Boxes (CDR-SB) scores are used to assess the influence of cognitive impairment on the ability to conduct everyday activities in patients with Alzheimer's disease and give a global clinical impression of the patient. CDR-SB Score values range from 0-18, with lower scores indicating better outcome.	Baseline, 24 months
Other	Exploratory: Change in functioning level: Instrumental Activities of Daily Living (IADL), unit on a scale	Activity of Daily Living, Lawton-Brody Scale. Self-reported questionnaire assessing the level of functioning in eight daily activities necessary for living in the community. For each activity, the participant is rated either dependent (0 points) or independent (1 point). The score ranges 0-8, with a higher score indicating a better outcome.	Baseline, 12 months, 24 months
Other	Exploratory: Change in blood pressure, mmHg	Changes in systolic and diastolic blood pressure, lower measurements indicate better outcomes	Baseline, 6 months, 12 months, 24 months
Other	Exploratory: Change in Body Mass Index (BMI), kg/m²	Calculated using baseline height, with lower BMI value indicating better outcome	Baseline, 6 months, 12 months, 24 months
Other	Exploratory: Change in waist circumference, cm	Lower waist circumference value indicating a better outcome	Baseline, 6 months, 12 months, 24 months
Other	Exploratory: Change in concentration of blood lipids - total cholesterol, mmol/l	Measured from serum, a lower total cholesterol value indicates a better outcome.	Baseline, 6 months, 12 months, 24 months
Other	Exploratory: Change in concentration of blood lipids - HDL, mmol/l	Measured from serum, a higher HDL value indicates a better outcome.	Baseline, 6 months, 12 months, 24 months
Other	Exploratory: Change in concentration of blood lipids - LDL, mmol/l	Measured from serum, a lower LDL value indicates a better outcome.	Baseline, 6 months, 12 months, 24 months
Other	Exploratory: Change in concentration of blood triglycerides, mmol/l	Measured from serum with lower triglycerides value indicating a better outcome.	Baseline, 6 months, 12 months, 24 months
Other	Exploratory: Change in concentration of plasma glucose, mmol/l	Measured from fasting blood sample, with lower glucose value indicating a better outcome.	Baseline, 6 months, 12 months, 24 months
Other	Exploratory: Change in concentration of glycated haemoglobin (HbA1c), %	Measured from fasting blood sample, with lower HbA1c value indicating a better outcome.	Baseline, 6 months, 12 months, 24 months
Other	Exploratory: Change in heart rate, bpm	Heart rate measured with Fitbit smartwatch	Continuously for 24 months
Other	Exploratory: Change in amount of social interaction (based on the total count of nearby Bluetooth devices)	Data on the total count of nearby Bluetooth devices collected via passive mobile phone sensors. Higher values indicate better outcome.	Continuously for 24 months
Other	Exploratory: Change in physical functioning: timed 10-meter dual-task test, gait speed in m/s and gait cost	Timed 10-meter dual task test combines a physical task (walking 10m) with a cognitive task (e.g., naming letters of the alphabet). The result is the time in seconds needed to complete this activity; gait speed is calculated in m/s. Shorter time and higher gait speed indicates a better outcome. Gait cost identifies the percentage of speed that is lost by adding a task to the walking and it is calculated as: GC= [(single-task gait velocity - dual-task gait velocity) / single-task gait velocity] × 100. Lower percentage indicates a better outcome.	Baseline, 24 months
Other	Exploratory: Change in physical functioning: Short Physical Performance Battery (SPPB), unit on a scale	Short Physical Performance Battery (SPPB) is a group of measures that combines the results of gait speed (score range 0-4), chair stand test (score range 0-4), and balance test (score range 0-4). The total score (sum of three domains) ranges from 0 to 12 (higher scores indicating better performance).	Baseline, 24 months
Other	Exploratory: Change in physical functioning: hand grip strength, kg	Hand grip strength using a handgrip dynamometer. Higher measures indicate a better outcome.	Baseline, 24 months
Other	Exploratory: Change in depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D), unit on a scale	The Center for Epidemiological Studies-Depression (CES-D) is a 20-item measure that asks how often over the past week symptoms associated with depression were experienced. Scores range from 0 to 60, with higher scores indicating greater depressive symptoms.	Baseline, 12 months, 24 months
Other	Exploratory: Change in sleep parameters based on Fitbit smartwatch data, unit on a scale	Changes in quantitative and qualitative parameters of sleep (sleep stages, duration, and fragmentation) measured by the Fitbit smartwatch	Continuously for 24 months
Other	Exploratory: Attitudes towards new technologies and novel digital solutions (System Usability Scale, SUS), unit on a scale	The SUS is a 10 item, widely used, psychometrically valid, and a simplified version is available for older adults with cognitive deficits. Scores are ranging 0-100 with higher scores indicating a better outcome.	1 month, 6 months, 24 months
Other	Exploratory: Change in serum concentration of neurofilament light chain, NFL, pg/ml	Blood levels of neurofilament light chain protein range from a minimum of 0, with lower levels indicating a better outcome.	Baseline, 24 months
Other	Exploratory: Change in serum concentration of pTau-181, ng/uL	Blood levels of phosphorylated tau-181 range from a minimum of 0, with lower levels indicating a better outcome.	Baseline, 24 months
Other	Exploratory: Change in brain imaging markers: volumetry of brain segments based on magnetic resonance imaging, MRI	Volumes of specific brain regions are assessed computationally.	Baseline, 24 months
Other	Exploratory: Change in brain imaging markers: white matter lesions	White matter lesion load is assessed computationally. Lower values indicate a better outcome.	Baseline, 24 months
Other	Exploratory: Change in brain imaging markers: brain atrophy and vascular load, based on widely used rating scales, units on a scale	Medial temporal lobe atrophy (MTA), global cortical atrophy (GCA) and Fazekas are assessed computationally. Lower scores indicate better outcomes.	Baseline, 24 months
Other	Exploratory: Participant experiences of the trial and the usability, acceptability, and feasibility of the digital intervention tools	Qualitative data on the study experiences and opinions about the intervention and the LETHE App will be collected through interviews/focus groups with a subgroup of the intervention group participants.	24 months
Primary	Feasibility: retention rate	Percentage of participants completing the 24-month trial period in each study arm. Higher percentage indicates a better outcome.	24 months
Primary	Feasibility: adherence to the structured multimodal lifestyle intervention	Attendance at scheduled intervention sessions (percentage), usage of / engagement with the digital devices (LETHE App, Fitbit smartwatch). Possible values range from a minimum of 0, with higher values indicating better adherence and more active engagement.	Continuously measured during 24 months
Primary	Change in dementia risk scores (LIBRA and CAIDE), units on a scale	Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score and Change in the LIfestyle for BRAin health (LIBRA) score are validated tools to estimate late-life dementia risk based on a combination of non-modifiable and modifiable risk factors (CAIDE) or modifiable factors only (LIBRA). Total score ranges from 0 to 15 (CAIDE) and from -5.9 to +12.7 (LIBRA). Higher scores indicate higher risk.	Baseline, 12 months, 24 months
Secondary	Change in healthy lifestyle, unit on a scale	Change in Healthy Lifestyle Index (brief score developed in the FINGER trial), a composite score based on self-reported data on exercise, diet, vascular factors, and cognitive/social activity (range 0-24, with a higher score indicating a better outcome)	Baseline, 12 months, 24 months
Secondary	Change in cognition: composite z-score based on an extended Neuropsychological Test Battery (NTB), unit on a scale	The NTB used in this study is adapted from the FINGER trial and includes the following tests: Wechsler Memory Scale Revised, WMS-III, WMS-R, logical memory, immediate; WMS-R logical memory, delayed; WMS-R visual paired associates, immediate; WMS-R visual paired associates, delayed; WMS-R Digit Span, total; Rey Auditory Verbal Learning Test, RAVLT, learning (free recall); RAVLT, delayed recall; CERAD category fluency; Category fluency (fruits and vegetables); Trail Making Test (TMT) A; Trail Making Test (TMT) B, shifting score B-A; Stroop Test, shortened 40-stimulus version, condition 2; Stroop Test, condition 3, interference score 3 - 2; Wechsler Adult Intelligence Scale (WAIS) Digit Symbol Substitution Test (DSST); Higher z-score indicates better outcome (better cognitive performance).	Baseline, 12 months, 24 months
Secondary	Change in stress-related symptoms (Perceived Stress Scale, PSS-14), unit on a scale	PSS is a 14-item self-report scale assessing stress-related symptoms. Values ranging 0-56, with lower scores indicating a better outcome.	Baseline, 12 months, 24 months
Secondary	Change in sleep problems (Insomnia Severity Index, ISI), unit on a scale	The Insomnia Severity Index (ISI) is a validated seven item assessment tool to assist in the clinical evaluation of insomnia complaints. Values ranging 0-28, with lower scores indicating a better outcome.	Baseline, 12 months, 24 months
Secondary	Change in health-related quality of life (RAND-36), unit on a scale	The RAND-36 is comprised of 36 items that assess eight health concepts. The scale values are ranging 0-100, with higher scores indicating a better outcome.	Baseline, 12 months, 24 months
Secondary	Change in health literacy (short version of the European Health Literacy Survey Questionnaire, HLS-EU-Q16), unit on a scale.	Health literacy will be assessed with the 16-item short version of the European Health Literacy Survey Questionnaire. Each item has four response categories (very difficult, fairly difficult, fairly easy and very easy), and higher scores indicate better health literacy.	Baseline, 24 months