Slowing Cognitive Decline in Alpha-synucleinopathies by Enhancing Physical Activity (ALPHA-FIT)

January 14, 2026 updated by: Dr. Michael Sommerauer, University Hospital, Bonn

α-Synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are the second most common neurodegenerative diseases. In addition to progressive motor deterioration, cognitive decline is a key element of the non-motor symptom complex of these diseases. Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) indicates an early stage of α-synucleinopathies, even before relevant motor or cognitive disorders are present. Therapeutic interventions in individuals with iRBD therefore have great preventive potential. In particular, increasing physical activity could have a relevant effect on neurodegenerative processes, including the preservation of cognitive functions.

The aim of the study is therefore to investigate the effects of increased physical activity in everyday life on cognitive functions in individuals with iRBD. In this randomized, double-blind, actively controlled study, an increase in physical activity will be implemented over a period of one year with the help of a motivational smartphone application. The intervention and control conditions are the same as those used in the Slow-SPEED trials, making the connection between the trials concrete. The primary outcome parameter is the change in cognitive performance in a neuropsychological test battery over one year.

Eighty individuals with iRBD and 50 age- and gender-matched individuals are being recruited at the University Hospital Bonn and the "Deutsches Zentrum für Neurodegenerative Erkrankungen" (DZNE) Bonn (German branch only). In addition to classic neuropsychological tests as the primary endpoint, magnetic resonance imaging (MRI) and blood-based markers of brain aging are being examined as secondary endpoints. This study is in close collaboration with the Slow-SPEED study (https://clinicaltrials.gov/study/NCT06993142). In addition, selected data from three separate trials-Alpha-Fit, Slow-SPEED-NL, and a sister trial in Austria currently in preparation-are planned to be synthesized into a meta-analysis.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

α-Synucleinopathies are the second most common group of neurodegenerative diseases after Alzheimer's disease (AD). Their prevalence is expected to increase significantly, with more than 12 million people worldwide likely to be affected by 2040. Clinical manifestations include Parkinson's disease (PD) and dementia with Lewy bodies (DLB). These diseases are characterized by neuronal inclusions of α-synuclein aggregates and Lewy bodies, which lead to premature aging of the brain. In addition to motor impairments, cognitive decline is a central element of non-motor symptoms, which not only occurs in DLB but also affects up to 80% of people with PD. Cognitive deficits can often occur in the early stages of the disease and significantly impair social functioning and quality of life. Despite their high prevalence, there are currently only a few therapeutic approaches for treating cognitive impairments in α-synucleinopathies. Therefore, easily accessible, early preventive interventions are crucial to counteract cognitive decline.

Isolated REM sleep behavior disorder (iRBD) is considered an early sign of α-synucleinopathy and can be reliably diagnosed using video polysomnography. Over 90% of individuals with iRBD develop either PD or DLB within 20 years of diagnosis, with an approximately equal distribution between the two entities. It is noteworthy that executive functions can often already be impaired in iRBD, which is associated with an increased risk of early conversion to PD or DLB. Thus, iRBD represents a phase of early neurodegeneration in which there is a high risk of cognitive decline. For this reason, individuals with iRBD are a particularly suitable target group for investigating the effects of lifestyle modifications that could slow the progression of the disease at an early stage.

Increasing physical activity could offer a promising way to slow the progression of neurodegenerative processes in the early stages of α-synucleinopathies. Since motor impairments are a central feature of PD and DLB, many affected individuals-even in the early stages of the disease-do not achieve the recommended level of physical activity. Studies on increasing physical activity have shown that physical training has positive effects on cerebrovascular function and cognitive performance, both in healthy aging and in various neurodegenerative diseases. For α-synucleinopathies in particular, there is evidence from animal models, observational studies, and clinical trials with up to six months of follow-up that physical activity may have disease-modifying effects. A recent meta-analysis in PD found that various interventions to increase physical activity have moderate effects on global cognition and even strong effects on executive functions. Therefore, promoting a more active lifestyle could be a promising strategy to positively influence the early course of α-synucleinopathies. Motivational mobile apps offer a novel way to increase physical activity, as they can be used completely independently, allowing for a high degree of scalability of the intervention.

Derivation of research questions

The following key questions will be addressed in the research project:

  • Can the progression of motor and cognitive changes in individuals with iRBD be influenced by increasing physical activity?
  • Does this intervention also affect biological and imaging markers of pathological brain aging?
  • Does this intervention also have an effect on healthy older people?

Study Type

Interventional

Enrollment (Estimated)

130

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Germany
    • North Rhine West-Falia
      • Bonn, North Rhine West-Falia, Germany, 53111
        • Recruiting
        • University Hospital of Bonn
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

iRBD:

  • Age: 50-80 years
  • Polysomnographically confirmed diagnosis of iRBD
  • Maximum of 120 minutes of sports/outdoor activities per day
  • Less than an average of 10,000 steps per day during the 4-week eligibility and baseline phase
  • Basic smartphone skills
  • Sufficient knowledge of German (native language, C1 or C2)
  • Ownership of a suitable smartphone (minimum screen size 4.6 inches, Android version 9 or iOS version 15 or newer)
  • Consent to be informed of any additional findings

Healthy controls:

  • Age: 50-80 years
  • Maximum of 120 minutes of sports/outdoor activities per day
  • Less than an average of 10,000 steps per day during the 4-week eligibility and baseline phase
  • Basic smartphone skills
  • Sufficient knowledge of German (native language, C1 or C2)
  • Ownership of a suitable smartphone (minimum screen size 4.6 inches, Android version 9 or iOS version 15 or newer)
  • Consent to be informed of any additional findings

Exclusion Criteria:

iRBD:

  • Relevant cardiovascular diseases
  • Problems with dexterity or cognitive impairments that make it difficult to use a smartphone
  • Cognitive impairments that limit the ability to make informed decisions and consent to participate in the study
  • Ownership of one of the following devices: Huawei P8 Lite, Huawei P9 Lite, Xiaomi Mi 6, Huawei P20 Lite (FitBit is not compatible)

Healthy controls:

  • Relevant cardiovascular diseases
  • Problems with dexterity or cognitive impairments that make it difficult to use a smartphone
  • Cognitive impairments that limit the ability to make informed decisions and consent to participate in the study
  • Ownership of one of the following devices: Huawei P8 Lite, Huawei P9 Lite, Xiaomi Mi 6, Huawei P20 Lite (FitBit is not compatible)
  • clinically diagnosed iRBD

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Doubling of baseline step count
Large increase in step count and moderate to vigorous physical activity relative to baseline level (+100%).
Behavioral: Increase of physical activity volume and intensity with the use of a motivational smartphone application
A motivational smartphone application will be available for all participants using their own smartphone: the Alpha-Fit app, comparable to the SLOW-SPEED app (https://clinicaltrials.gov/study/NCT06993142). The Alpha-Fit app will motivate participants to increase the volume and intensity of their physical activity in daily life over a long period of time (12 months) based on their own baseline levels. Different treatment arms will receive different physical activity goals. The app offers participants feedback and support, that will stimulate them to reach their individual physical activity goal (i.e. incremental relative increase of step count and minutes exerting ≥ 64% of maximum heart rate reflecting moderate-to-vigorous physical activity (MVPA) relative to baseline level).
Other Names:
  • Motivational movement intervention
Active Comparator: Small increase of baseline step count
Small increase in step count and moderate to vigorous physical activity relative to baseline level (+10%).
Behavioral: Increase of physical activity volume and intensity with the use of a motivational smartphone application
A motivational smartphone application will be available for all participants using their own smartphone: the Alpha-Fit app, comparable to the SLOW-SPEED app (https://clinicaltrials.gov/study/NCT06993142). The Alpha-Fit app will motivate participants to increase the volume and intensity of their physical activity in daily life over a long period of time (12 months) based on their own baseline levels. Different treatment arms will receive different physical activity goals. The app offers participants feedback and support, that will stimulate them to reach their individual physical activity goal (i.e. incremental relative increase of step count and minutes exerting ≥ 64% of maximum heart rate reflecting moderate-to-vigorous physical activity (MVPA) relative to baseline level).
Other Names:
  • Motivational movement intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive Performance: Change in mild cognitive impairment (MCI) in PD Level II Criteria
Time Frame: 12 months

Change in cognitive performance between the start of the study (baseline) and the time after the intervention (after 12 months of intervention), measured as the global mean of the results from a neuropsychological test battery according to MCI in PD Level II criteria.

Executive functions:

  • semantic word fluency
  • set-shifting abilities
  • inhibition
  • logical thinking

Visual cognitive abilities:

  • spatial perception
  • working memory performance
  • processing speed
  • attention

Memory functions:

  • verbal memory
  • visuospatial memory

Linguistic abilities:

  • naming semantic
  • abstract thinking
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in body composition
Time Frame: 12 months
Change in body composition measured through MRI sequences and bio-electric impedance analysis.
12 months
Motor functions: Change in Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III
Time Frame: 12 months
Change in score which ranges from 0 to 108. Higher score indicates greater motor impairment.
12 months
Motor functions: Change Perdue-Pegboard-Test
Time Frame: 12 months
Change in score. Higher scores indicates better manual dexterity and hand coordination.
12 months
Motor functions: Change in digital testing outcomes
Time Frame: 12 months
Change in digital testing assessment, funded by the European Research Council (ERC) (https://cordis.europa.eu/project/id/101169580).
12 months
Sleep behavior: Change in subjective sleep quality
Time Frame: 12 months
Change in Pittsburgh Sleep Quality Index (PSQI), with scores between 0 and 21, higher scores indicate worse sleep.
12 months
Sleep behavior: Change in Polysomnography (PSG) read-outs
Time Frame: 12 months
Change in PSG read-outs.
12 months
Change in blood-based markers for metabolism.
Time Frame: 12 months
Change found in biomarkers in plasma, serum and peripheral blood mononuclear cells (PBMCs).
12 months
Change in blood-based markers for neurodegeneration.
Time Frame: 12 months
Change found in biomarkers in plasma, serum and PBMCs
12 months
Change in blood-based markers for inflammation.
Time Frame: 12 months
Change found in biomarkers in plasma, serum and PBMCs
12 months
Cognitive performance: Change in performance in digital app
Time Frame: 12 months
Change in performance in the https://www.neuronation.com/ app. Will be measured in 2-week intervals.
12 months
Change in Quantitative MRI Measures of Brain Structure and Function
Time Frame: 12 months
Change from baseline to 12 months in MRI-derived quantitative measures of brain structure and function, including resting-state functional magnatic resonance imaging (fMRI), T1-weighted structural measures, fluid-attenuated inversion recovery (FLAIR) based measures, quantitative susceptibility mapping (QSM) metrics, and neuromelanin-sensitive MRI signal measures.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bonn

Collaborators

Radboud University Medical Center
Medical University Innsbruck
IJsfontein B.V., Netherlands
Synaptikon GmbH
Parkinson Stiftung

Investigators

  • Principal Investigator: Michael B Sommerauer, Dr., University Hospital of Bonn

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 4, 2025

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

December 22, 2025

First Submitted That Met QC Criteria

December 22, 2025

First Posted (Estimated)

January 7, 2026

Study Record Updates

Last Update Posted (Estimated)

January 16, 2026

Last Update Submitted That Met QC Criteria

January 14, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-289-BO
  • 101095426 (Other Grant/Funding Number: European Union under the Horizon Europe Fostering a European Research Area for Health Research (ERA4Health))
  • 01EA2501 (Other Grant/Funding Number: Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We will make relevant anonymised data available in a database.

IPD Sharing Time Frame

We will make relevant anonymised data available in a database after publication of the main results of our trial.

IPD Sharing Access Criteria

Researchers who are interested in re-use of the data are asked to contact the central contact person for permission.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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