Multimodal Imaging Study on Physical Activity in Patients With Alzheimer's Disease

NCT03939286 | Unknown

• 1 other identifier: 19-064
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to gain a better understanding of metabolic early changes in neurodegenerative diseases, in order to enable new diagnostic and therapeutic approaches in the future. Further, it aims to identify specific movement-induced changes at the cerebral level, on cognition, on quality of life and physical fitness, and on serology parameters in neurodegenerative diseases. In general, valid biomarkers are needed for early diagnosis and prediction of disease progression. It has been hypothesized that metabolic changes may precede structural changes and may be examined by intervention with exercise therapy. The non-invasive, in vivo characterization and diagnosis of such metabolic changes is therefore of paramount importance. In this line, this research project is focused on applying magnetic resonance imaging (MRI) based metabolic imaging techniques such as sodium MRI and phosphorus magnetic resonance spectroscopy (MRS) with standard structural and functional MRI methods, combined with exercise training, in order to detect biomarkers early in different stages of neurodegenerative diseases. Moreover, this project aims to examine the sensitivity of metabolic imaging with sodium and phosphorus sequences over classical MRI imaging with whole body fat sequences, in order to detect cerebral alterations. At the end, the medical benefit of the planned project lies in the fact that the expected findings are groundbreaking for the understanding of the phenomenology and pathobiology of neurodegenerative diseases. This is the basis for the development of new methods for early diagnosis and individualized medicine with the optimization of future treatment options.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (3)

• Metabolic changes of the brain induced by intervention program

  Sodium MR Imaging

  T1 (baseline), T3 (6 months, after intervention), T4 (optional, 1 year after intervention)

• Metabolic changes of the brain induced by intervention program

  Phosphor MR Imaging

  T1 (baseline), T3 (6 months, after intervention), T4 (optional, 1 year after intervention)

• Structural changes of the brain induced by intervention program

  Standard MR Imaging

  T1 (baseline), T3 (6 months, after intervention), T4 (optional, 1 year after intervention)

Study Arms (2)

movement group

OTHER

intensified training (equipment, coordination, balance)

Other: Clinical-neurological and neuropsychological tests; Diagnostic Test: Blood sampling; Other: Assessment of physical activity via fitness tracker/diary; Other: MRI-examinations

control group

OTHER

continuation of physical activity as usual

Other: Clinical-neurological and neuropsychological tests; Diagnostic Test: Blood sampling; Other: Assessment of physical activity via fitness tracker/diary; Other: MRI-examinations

Interventions

Clinical-neurological and neuropsychological tests OTHER

The tests include established standardized questionnaires and detailed clinical neuropsychological examinations (e.g., tests on cognition and perception). In order to avoid exercise effects in multiple examinations, so-called parallel procedures should be used.

control group; movement group

Blood sampling DIAGNOSTIC_TEST

Venous blood sampling (40 ml) is performed according to the usual criteria of sterile working at baseline and after intervention.

control group; movement group

Assessment of physical activity via fitness tracker/diary OTHER

All study participants, regardless of group classification, are randomly selected for a period of one week using Fitbit Charge 2® fitness trackers. The study participants are asked in this context to pursue their regular activity and to wear the bracelets for a week throughout. All study participants are asked to document their activities in a hand-written diary.

control group; movement group

MRI-examinations OTHER

Standard MRI-methods, Sodium MRI, Phosphor MRS, Wholebody-Fat-MRI

control group; movement group

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• prodromal or early symptomatic Alzheimer's disease according to the S3 guidelines of the German Society of Neurology in relation to the IWG-2 criteria for the definition of probable Alzheimer's disease
• Age between 50 and 80 years
• Mini Mental State Examination (MMSE)\> 19 (screening at least 12 weeks before baseline visit)
• Cognitive ability to understand the task as well as regular participation in exercise program, based on assessment of the treating neurologist and / or neuropsychologist
• For antidementive or antidepressant medication, stable medication for at least 30 days
• No visual or auditory limitation preventing participation in cognitive and functional testing
• Interested in regular participation for 6 months, doing domestic exercises
• Presence of a written informed consent

You may not qualify if:

• Heart attack or evidence of coronary heart disease (angina) in the last 2 years
• Severe systemic disease, which is expected to worsen during exercise
• Difficult to adjust diabetes mellitus II
• Difficult to set art. Hypertension in the last 6 months
• Severe psychiatric illness
• Severe orthopedic disease
• Alcohol and / or drug abuse in the last 2 years
• Chronic pain and / or musculoskeletal disease, which prevent regular physical activity
• Acute fracture or orthopedic injury last month
• cancer in the last 5 years (except basal cell and spinal cell carcinoma) Contraindications for MRI examination below 3 Tesla (for example, implantation of ferromagnetic parts) For study participants, the following measures must be observed due to the direct effects of the magnetic field, in particular the force exerted on para- or ferromagnetic bodies: Study participants with incorporated metallic implants are not admitted. Pregnancy or lactation, traumatic brain injury, neurological or psychiatric disorders (other than the neurological disease to be studied for patients), relevant and severe other medical conditions, e.g. metabolic, endocrinological or cardiac disorders, mental retardation, magnetic metal implants (also intrauterine spiral).
• Diseases:
• epilepsy
• severe cardiac pre-existing conditions
• Musculoskeletal disorders that are contrary to regular exercise
• advanced osteoporosis

Sponsors & Collaborators

• RWTH Aachen University: lead

Study Sites (1)

RWTH Aachen University Hospital

Aachen, North Rhine-Westphalia, 52074, Germany

RECRUITING

Related Publications (10)

• Beckett MW, Ardern CI, Rotondi MA. A meta-analysis of prospective studies on the role of physical activity and the prevention of Alzheimer's disease in older adults. BMC Geriatr. 2015 Feb 11;15:9. doi: 10.1186/s12877-015-0007-2.

  PMID: 25887627 BACKGROUND

• Bruggemann N, Hagenah J, Reetz K, Schmidt A, Kasten M, Buchmann I, Eckerle S, Bahre M, Munchau A, Djarmati A, van der Vegt J, Siebner H, Binkofski F, Ramirez A, Behrens MI, Klein C. Recessively inherited parkinsonism: effect of ATP13A2 mutations on the clinical and neuroimaging phenotype. Arch Neurol. 2010 Nov;67(11):1357-63. doi: 10.1001/archneurol.2010.281.

  PMID: 21060012 BACKGROUND

• Diehl-Wiesenecker E, von Armin CA, Dupuis L, Muller HP, Ludolph AC, Kassubek J. Adipose Tissue Distribution in Patients with Alzheimer's Disease: A Whole Body MRI Case-Control Study. J Alzheimers Dis. 2015;48(3):825-32. doi: 10.3233/JAD-150426.

  PMID: 26402111 BACKGROUND

• Hilker R, Klein C, Ghaemi M, Kis B, Strotmann T, Ozelius LJ, Lenz O, Vieregge P, Herholz K, Heiss WD, Pramstaller PP. Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene. Ann Neurol. 2001 Mar;49(3):367-76.

  PMID: 11261512 BACKGROUND

• Reetz K, Lencer R, Steinlechner S, Gaser C, Hagenah J, Buchel C, Petersen D, Kock N, Djarmati A, Siebner HR, Klein C, Binkofski F. Limbic and frontal cortical degeneration is associated with psychiatric symptoms in PINK1 mutation carriers. Biol Psychiatry. 2008 Aug 1;64(3):241-7. doi: 10.1016/j.biopsych.2007.12.010. Epub 2008 Feb 7.

  PMID: 18261714 BACKGROUND

• Reetz K, Lencer R, Hagenah JM, Gaser C, Tadic V, Walter U, Wolters A, Steinlechner S, Zuhlke C, Brockmann K, Klein C, Rolfs A, Binkofski F. Structural changes associated with progression of motor deficits in spinocerebellar ataxia 17. Cerebellum. 2010 Jun;9(2):210-7. doi: 10.1007/s12311-009-0150-4.

  PMID: 20016963 BACKGROUND

• Raj A, Kuceyeski A, Weiner M. A network diffusion model of disease progression in dementia. Neuron. 2012 Mar 22;73(6):1204-15. doi: 10.1016/j.neuron.2011.12.040. Epub 2012 Mar 21.

  PMID: 22445347 BACKGROUND

• Warren JD, Rohrer JD, Hardy J. Disintegrating brain networks: from syndromes to molecular nexopathies. Neuron. 2012 Mar 22;73(6):1060-2. doi: 10.1016/j.neuron.2012.03.006. Epub 2012 Mar 21.

  PMID: 22445334 BACKGROUND

• Zhou J, Gennatas ED, Kramer JH, Miller BL, Seeley WW. Predicting regional neurodegeneration from the healthy brain functional connectome. Neuron. 2012 Mar 22;73(6):1216-27. doi: 10.1016/j.neuron.2012.03.004. Epub 2012 Mar 21.

  PMID: 22445348 BACKGROUND

• Jucker M, Walker LC. Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol. 2011 Oct;70(4):532-40. doi: 10.1002/ana.22615.

  PMID: 22028219 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Neuropsychological Tests; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychological Tests; Behavioral Disciplines and Activities; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jörg B. Schulz, Prof. Dr.

  Clinic for neurology University Hospital Aachen

  STUDY DIRECTOR

Central Study Contacts

Kathrin Reetz, Prof. Dr.

CONTACT

+49(0)241-80 36516; kreetz@ukaachen.de

Alexa Häger, Dr. med.

CONTACT

+49(0)241-80 37212; ahaeger@ukaachen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In total, about 50 study participants will be examined in a prodromal or symptomatic early stage of Alzheimer's disease. These should be distributed equally randomized into two groups: a movement group (n = 25) with intensified training (equipment, coordination, balance) and a control group with continuation of physical activity as usual and participation in a psychoeducational program (n = 25).

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: May 6, 2019
• Study Start: April 8, 2019
• Primary Completion: April 1, 2021
• Study Completion: October 1, 2021
• Last Updated: May 7, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)