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

NCT ID: NCT03939286

Last Updated: 2019-05-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-08

Study Completion Date

2021-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Alzheimer Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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movement group

intensified training (equipment, coordination, balance)

Group Type OTHER

Clinical-neurological and neuropsychological tests

Intervention Type 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.

Blood sampling

Intervention Type DIAGNOSTIC_TEST

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

Assessment of physical activity via fitness tracker/diary

Intervention Type 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.

MRI-examinations

Intervention Type OTHER

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

control group

continuation of physical activity as usual

Group Type OTHER

Clinical-neurological and neuropsychological tests

Intervention Type 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.

Blood sampling

Intervention Type DIAGNOSTIC_TEST

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

Assessment of physical activity via fitness tracker/diary

Intervention Type 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.

MRI-examinations

Intervention Type OTHER

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

Interventions

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Clinical-neurological and neuropsychological tests

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.

Intervention Type OTHER

Blood sampling

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

Intervention Type DIAGNOSTIC_TEST

Assessment of physical activity via fitness tracker/diary

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.

Intervention Type OTHER

MRI-examinations

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

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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).

Furthermore, the spatial conditions in the magnet do not allow to examine persons with certain back complaints or a strong overweight. As a rule, a body mass index (BMI, weight \[kg\] / size2 \[cm2\]) of \> 30 is the exclusion criterion. With regard to the participation in the exercise in advance with unclear suitability is a consultation with the attending family doctor regarding possible contraindications, which are a regular participation in a sports program in the way.


Diseases:

* epilepsy
* severe cardiac pre-existing conditions
* Musculoskeletal disorders that are contrary to regular exercise
* advanced osteoporosis
* Increased fall risk / imbalance
* Advanced Heart Failure, Shortness of Breath, Severe Pulmonary Disease, which are contrary to regular physical activity
* Diabetes mellitus prone to hypoglycaemia and hyperglycemia

Conditions:

* pregnancy
* Uncertain knowledge about possibly existing pregnancy

Contraceptives:

* Any type of intrauterine device
* Spiral made of copper Metal-containing implants or devices in / on the body (all non-metal implants / devices / patches will undergo a thorough examination based on the MRI Safety

Listing www.mrisafety.com):

* Pacemaker / implanted pacemaker wires
* Implanted defibrillator
* Drug pump / infusion device
* Stimulation device / electrodes

Non-MRI-compatible implants, for example, surgical screws, plates, nails, etc:

* vascular / lumen filters, wire rings, wire spirals, stents, vascular clips
* Artificial heart valve
* Transdermal patches
* epithesis (or partial epithesis)
* shunts, catheters, wire sutures

Metal in / on the body:

* Splinter / gunshot wounds
* Metal shards in the eye, even if everything was supposedly removed
* Piercing

Dental metals:

* Any type of implant in the jawbone area / dental implant older than 20 years
* No contraindications: Amalgam fillings, inlays, crowns, single crowned teeth as a denture base for a denture termed a telescopic denture, firmly screwed dentures

Additional:

* cochlear implant
* Ventilation Tubes
* tattoos / permanent make-up (only after the most exact examination and special approval see separate explanation)
Minimum Eligible Age

50 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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RWTH Aachen University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jörg B. Schulz, Prof. Dr.

Role: STUDY_DIRECTOR

Clinic for neurology University Hospital Aachen

Locations

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RWTH Aachen University Hospital

Aachen, North Rhine-Westphalia, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Kathrin Reetz, Prof. Dr.

Role: CONTACT

+49(0)241-80 36516

Alexa Häger, Dr. med.

Role: CONTACT

+49(0)241-80 37212

Facility Contacts

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Kathrin Reetz

Role: primary

+4902418036516 ext. +4902418036516

Alexa Häger

Role: backup

+4902418037212 ext. +4902418037212

References

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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.

Reference Type BACKGROUND
PMID: 25887627 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21060012 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26402111 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11261512 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18261714 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20016963 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22445347 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22445334 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22445348 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22028219 (View on PubMed)

Other Identifiers

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19-064

Identifier Type: -

Identifier Source: org_study_id

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