Slowing Cognitive Decline in Alpha-synucleinopathies by Enhancing Physical Activity

NCT07324330 | Recruiting

• 3 other identifiers: 2025-289-BO01EA2501101095426
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease; Prodromal Stage; Neurodegenerative Diseases; Basal Ganglia Diseases; Central Nervous System Diseases; Synucleinopathies; Nervous System Diseases; Cerebral Disorder; Brain Diseases; Parkinsonian Disorders

Keywords

intervention; movement; iRBD; prodromal parkinson's; non-pharmacologic; alpha-synucleinopathy; biomarker; cognitive decline; executive function; MRI; lifestyle; prevention; RCT; motor decline; smartphone; smartwatch; accelerometer; scalable; prodromal; PD; Parkinson; Lewy-body; MSA; multiple system atrophy; dementia

Outcome Measures

Primary Outcomes (1)

• Cognitive Performance: Change in mild cognitive impairment (MCI) in PD Level II Criteria

  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 Outcomes (11)

• Motor functions: Change in Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III

  12 months

• Motor functions: Change Perdue-Pegboard-Test

  12 months

• Motor functions: Change in digital testing outcomes

  12 months

• Change in body composition

  12 months

• Sleep behavior: Change in subjective sleep quality

  12 months

Study Arms (2)

Doubling of baseline step count

EXPERIMENTAL

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

Small increase of baseline step count

ACTIVE COMPARATOR

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

Interventions

Increase of physical activity volume and intensity with the use of a motivational smartphone application BEHAVIORAL

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).

Also known as: Motivational movement intervention

Doubling of baseline step count; Small increase of baseline step count

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University Innsbruck: collaborator
• IJsfontein B.V., Netherlands: collaborator
• Parkinson Stiftung: collaborator
• University Hospital, Bonn: lead
• Radboud University Medical Center: collaborator
• Synaptikon GmbH: collaborator

Study Sites (1)

University Hospital of Bonn

Bonn, North Rhine West-Falia, 53111, Germany

RECRUITING

Related Publications (15)

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  PMID: 22275317 BACKGROUND

• Kim R, Lee TL, Lee H, Ko DK, Lee JH, Shin H, Lim D, Jun JS, Byun K, Park K, Jeon B, Kang N. Effects of physical exercise interventions on cognitive function in Parkinson's disease: An updated systematic review and meta-analysis of randomized controlled trials. Parkinsonism Relat Disord. 2023 Dec;117:105908. doi: 10.1016/j.parkreldis.2023.105908. Epub 2023 Oct 26.

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  PMID: 31266451 BACKGROUND

• Jellinger KA, Korczyn AD. Are dementia with Lewy bodies and Parkinson's disease dementia the same disease? BMC Med. 2018 Mar 6;16(1):34. doi: 10.1186/s12916-018-1016-8.

  PMID: 29510692 BACKGROUND

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  PMID: 35970584 BACKGROUND

• Höglinger, G. U. et al. Towards a Biological Definition of Parkinson's Disease. Preprint at https://doi.org/10.20944/preprints202304.0108.v1 (2023).

  BACKGROUND

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• Dorsey ER, Sherer T, Okun MS, Bloem BR. The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis. 2018;8(s1):S3-S8. doi: 10.3233/JPD-181474.

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• de Vries NM, Darweesh SKL, Bloem BR. Citius, Fortius, Altius-Understanding Which Components Drive Exercise Benefits in Parkinson Disease. JAMA Neurol. 2021 Dec 1;78(12):1443-1445. doi: 10.1001/jamaneurol.2021.3744. No abstract available.

  PMID: 34724528 BACKGROUND

• Dauvilliers Y, Schenck CH, Postuma RB, Iranzo A, Luppi PH, Plazzi G, Montplaisir J, Boeve B. REM sleep behaviour disorder. Nat Rev Dis Primers. 2018 Aug 30;4(1):19. doi: 10.1038/s41572-018-0016-5.

  PMID: 30166532 BACKGROUND

• Cesari M, Heidbreder A, St Louis EK, Sixel-Doring F, Bliwise DL, Baldelli L, Bes F, Fantini ML, Iranzo A, Knudsen-Heier S, Mayer G, McCarter S, Nepozitek J, Pavlova M, Provini F, Santamaria J, Sunwoo JS, Videnovic A, Hogl B, Jennum P, Christensen JAE, Stefani A. Video-polysomnography procedures for diagnosis of rapid eye movement sleep behavior disorder (RBD) and the identification of its prodromal stages: guidelines from the International RBD Study Group. Sleep. 2022 Mar 14;45(3):zsab257. doi: 10.1093/sleep/zsab257.

  PMID: 34694408 BACKGROUND

• Bliss ES, Wong RH, Howe PR, Mills DE. Benefits of exercise training on cerebrovascular and cognitive function in ageing. J Cereb Blood Flow Metab. 2021 Mar;41(3):447-470. doi: 10.1177/0271678X20957807. Epub 2020 Sep 20.

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• Berg D, Borghammer P, Fereshtehnejad SM, Heinzel S, Horsager J, Schaeffer E, Postuma RB. Prodromal Parkinson disease subtypes - key to understanding heterogeneity. Nat Rev Neurol. 2021 Jun;17(6):349-361. doi: 10.1038/s41582-021-00486-9. Epub 2021 Apr 20.

  PMID: 33879872 BACKGROUND

• Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, Bottacchi E, Cannas A, Ceravolo G, Ceravolo R, Cicarelli G, Gaglio RM, Giglia RM, Iemolo F, Manfredi M, Meco G, Nicoletti A, Pederzoli M, Petrone A, Pisani A, Pontieri FE, Quatrale R, Ramat S, Scala R, Volpe G, Zappulla S, Bentivoglio AR, Stocchi F, Trianni G, Dotto PD; PRIAMO study group. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord. 2009 Aug 15;24(11):1641-9. doi: 10.1002/mds.22643.

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• Aarsland D, Batzu L, Halliday GM, Geurtsen GJ, Ballard C, Ray Chaudhuri K, Weintraub D. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers. 2021 Jul 1;7(1):47. doi: 10.1038/s41572-021-00280-3.

  PMID: 34210995 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Prodromal Symptoms; Neurodegenerative Diseases; Basal Ganglia Diseases; Central Nervous System Diseases; Synucleinopathies; Nervous System Diseases; Brain Diseases; Parkinsonian Disorders; Cognitive Dysfunction; Multiple System Atrophy; Dementia

Condition Hierarchy (Ancestors)

Movement Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Primary Dysautonomias; Autonomic Nervous System Diseases

Study Officials

• Michael B Sommerauer, Dr.

  University Hospital of Bonn

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin M Rodemann

CONTACT

+49 0228 287 - 19436; Martin.Rodemann@ukbonn.de

Emily L Fitzgibbon, M.Sc.

CONTACT

Emily.Fitzgibbon@ukbonn.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant Physician, Head of the Sleep Laboratory

Study Record Dates

• First Submitted: December 22, 2025
• First Posted: January 7, 2026
• Study Start: December 4, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: We will make relevant anonymised data available in a database after publication of the main results of our trial.
• Access Criteria: Researchers who are interested in re-use of the data are asked to contact the central contact person for permission.

Locations

DE (1)