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Alzheimer DiseaseNCT03030365

Orientation in AD Patients: PET-MR Study

An observational study of Alzheimer Disease and Mild Cognitive Impairment, run by Assuta Medical Center.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Despite the high prevalence of Alzheimer's disease (AD), its underlying mechanisms remain poorly understood. An emerging body of evidence supports disorientation as an early marker for AD-related neurodegeneration. Read more about this study

Who is it for?
Ages 50 to 79 years
Conditions the study is for
Alzheimer Disease, Mild Cognitive Impairment
What is being tested?
Siemens "Biograph mMR" PET-MR (3T)
How many people
30 participants
Where
No sites listed yet
Study dates
15 Feb 2017to 15 Feb 2020
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: The study Population includes patients diagnosed as amnestic mild cognitively impaired, patients suffering from Alzheimer's disease, and age-matched healthy controls.

Who may be able to join

  • subjects aged 50-79 years.
  • patients suffering from memory disorder.
  • Test score mini-mental state examinations higher than 20.

Who cannot join

  • Contraindication to MR imaging
  • pregnant women.
  • patients with contraindications for injection of gadolinium.

Trial locations and contacts

No sites are listed yet.

David Groshar, MD contact

+972-37645497

davidg@assuta.co.il

About this study

Official title: The Orientation System, the Default-network and Brain Metabolism in Patients With Early Stage Alzheimer's Disease: a Multimodal Functional Study.

Despite the high prevalence of Alzheimer's disease (AD), its underlying mechanisms remain poorly understood. An emerging body of evidence supports disorientation as an early marker for AD-related neurodegeneration. In this study we intend to collect, coregister and analyze Positron Emission Tomography (PET) and , functional and structural magnetic resonance imaging (MRI, fMRI) data from AD-spectrum patients to establish orientation as core disturbance in AD.

Read the detailed description

As population aging is progressively contributing to the global burden of dementia, Alzheimer's disease (AD) is gaining recognition as a health-and social-care priority. Evidence converging from recently published works as well as our own preliminary results, propose that orientation is a sensitive marker for preclinical AD-related neurodegeneration.

Our behavioral results show a simple orientation test to surpass currently used neuropsychological tests in classification of patients along the AD spectrum. A subsequential fMRI study revealed the orientation task to preferentially recruit brain regions identified as susceptible to early AD-related cortical atrophy, including the posterior cingulate cortex, parietooccipital sulcus and hippocampus bilaterally, as well as to significantly overlap with the default mode network (DMN) - a set of interconnected brain regions which were independently recognized as highly perturbed in AD.

In an attempt to further support the role of orientation in AD we propose to use co-registration of several modalities of neuroimaging in patients with AD, mild cognitive impairment (MCI) and healthy controls (HC): resting-state fMRI, task-fMRI, structural MRI and co-registered PET.

  1. Resting-state functional magnetic resonance (fMRI) imaging detecting temporally synchronous, spatially distributed, spontaneous low frequency blood-oxygen level-dependent signal fluctuations in task-free settings, that are further clustered into maps of functional large-scale neural networks. A major network revealed in rest is the default DMN. DMN includes the posterior cingulate (PCC), inferior parietal (IPL), lateral (LTC) and medial temporal (MTL), and medial prefrontal cortical regions (MPFC), and is known to be involved in self-referential processes including introspection, memory retrieval, daydreaming and orientation.
  2. Task fMRI - using this module we recently demonstrated that fMRI activation generated by orientation task in the person, space and time domains activated the PCC, IPL, and MPFC and MTL hubs of the DMN. This task is now to be applied in patients with AD.
  3. Structural MRI - a decrease in hippocampus volume is an early imaging finding followed by cortical atrophy as AD progresses.
  4. PET - FDG-PET (glucose metabolism) is known to show temporo-parietal hypometabolism in AD.

Considered these findings alongside ongoing research at the dynamics of anatomical and functional AD associated brain dysfunction, we propose a thorough, and to the best of our knowledge, a never before attempted study aimed at linking markers for AD pathology (cortical atrophy, decrease of functional connectivity, cerebral glucose metabolism) to the disruption of specific cognitive faculties, particularly orientation in the space, time and person domains.

Being tested
Siemens "Biograph mMR" PET-MR (3T)
Keywords
Orientation, Disorientation.
Medical subject headings
Alzheimer Disease, Cognitive Dysfunction, Orientation, Spatial, Confusion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Siemens "Biograph mMR" PET-MR (3T)Device

    Standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi of 18F-FDG prior to PET MRI.

Study groups in NCT03030365
Study groupRoleWhat they receive
Healthy ControlsAge matched controls for the various clinical groups will undergo standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi (millicurie) of 18F (fluorodeoxyglucose) -FDG prior to PET MRI, using "Biograph mMR" PET-MR (3T).
Receives: Device: Siemens "Biograph mMR" PET-MR (3T)
Amnestic Mild cognitive impairedPatients diagnosed with mild cognitive impairment, exhibiting impairment mostly in memory that is significant but does not interfere with everyday activities. Subjects will undergo standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi of 18F-FDG prior to PET MRI, using "Biograph mMR" PET-MR (3T).
Receives: Device: Siemens "Biograph mMR" PET-MR (3T)
Alzheimer's disease patientsPatients exhibiting significant loss of intellectual ability that interferes with everyday functioning that meet Alzheimer's pattern of decline, and following exclusion of alternative neurodegenerative, cerebrovascular, and metabolic etiologies. Subjects will undergo standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi of 18F-FDG prior to PET MRI, using "Biograph mMR" PET-MR (3T).
Receives: Device: Siemens "Biograph mMR" PET-MR (3T)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Orientation performance

    Evaluation of Performance in orientation task using success rate and response time. Response time and success rate would be combined into an efficacy score: success rate-response time quotient, measured in units of second^-1. A primary effort in this work is to establish a model that links all primary Outcome Measures, in an attempt to examine how pathological markers predict cognitive performance and weather there relations are modulated by fMRI activity.

    Measured: 1 day

  2. Cortical atrophy

    Cortical atrophy will be evaluated by applying voxel-based morphometry analysis on T1-weighted images. This outcome would be evaluated as number of voxels significantly different from from a distribution of corresponding voxels gathered from a healthy control cohort. significantly different voxels would be considered atrophic.

    Measured: 1 Day

  3. Functional connectivity analysis

    Functional connectivity measurements within and between functional networks. This outcome would be evaluated by using correlation values computed between single voxels/region of interest, such that correlation values reflect integrity of functional networks.

    Measured: 1 Day

  4. Mental-orientation evoked fMRI activity

    Contrasting mental-orientation evoked activity between controls , MCIs and AD. This outcome would be evaluated by applying a contrast between fMRI patterns of activity evoked by the mental-orientation task in clinical groups (AD and MCI) to their control counterparts, to reveal the number and location of voxels showing reduced or increased activity in mental-orientation processing.

    Measured: 1 Day

  5. [18]F-fluorodeoxyglucose (FDG) uptake

    [18]F-fluorodeoxyglucose glucose analog uptake is measured using positron emission tomography, and is regarded as a marker for neural activity. This outcome would be evaluated by normalizing FDG absorption values and examining voxels statistically different in their metabolic activity relative to highly validated norms.

    Measured: 1 Day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2017 (estimated)
  2. Study start15 Feb 2017 (estimated)
  3. Primary completion15 Feb 2019 (estimated)
  4. Study completion15 Feb 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Cross-sectional
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03030365
Sponsor's protocol ID
AssutaMC
Status last verified
Jan 2017
First submitted
8 Jan 2017
Last updated
25 Jan 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided: Only in the case where publication of coded data is required\\encouraged by the Journal for publication

Publications

  • Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.

    PubMed 21514249
  • Arzy S, Collette S, Ionta S, Fornari E, Blanke O. Subjective mental time: the functional architecture of projecting the self to past and future. Eur J Neurosci. 2009 Nov;30(10):2009-17. doi: 10.1111/j.1460-9568.2009.06974.x. Epub 2009 Nov 11.

    PubMed 19912333
  • Berrios GE. Disorientation states and psychiatry. Compr Psychiatry. 1982 Sep-Oct;23(5):479-91. doi: 10.1016/0010-440x(82)90161-4. No abstract available.

    PubMed 7140264
  • Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, Sheline YI, Klunk WE, Mathis CA, Morris JC, Mintun MA. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005 Aug 24;25(34):7709-17. doi: 10.1523/JNEUROSCI.2177-05.2005.

    PubMed 16120771
  • deIpolyi AR, Rankin KP, Mucke L, Miller BL, Gorno-Tempini ML. Spatial cognition and the human navigation network in AD and MCI. Neurology. 2007 Sep 4;69(10):986-97. doi: 10.1212/01.wnl.0000271376.19515.c6.

    PubMed 17785667
  • Jheng SS, Pai MC. Cognitive map in patients with mild Alzheimer's disease: a computer-generated arena study. Behav Brain Res. 2009 Jun 8;200(1):42-7. doi: 10.1016/j.bbr.2008.12.029. Epub 2008 Dec 31.

    PubMed 19162077
  • Kunz L, Schroder TN, Lee H, Montag C, Lachmann B, Sariyska R, Reuter M, Stirnberg R, Stocker T, Messing-Floeter PC, Fell J, Doeller CF, Axmacher N. Reduced grid-cell-like representations in adults at genetic risk for Alzheimer's disease. Science. 2015 Oct 23;350(6259):430-3. doi: 10.1126/science.aac8128.

    PubMed 26494756
  • McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.

    PubMed 21514250
  • Monacelli AM, Cushman LA, Kavcic V, Duffy CJ. Spatial disorientation in Alzheimer's disease: the remembrance of things passed. Neurology. 2003 Dec 9;61(11):1491-7. doi: 10.1212/wnl.61.11.1491.

    PubMed 14663030
  • Peer M, Salomon R, Goldberg I, Blanke O, Arzy S. Brain system for mental orientation in space, time, and person. Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):11072-7. doi: 10.1073/pnas.1504242112. Epub 2015 Aug 17.

    PubMed 26283353

Questions about this trial

What is this clinical trial studying?

An observational study of Alzheimer Disease and Mild Cognitive Impairment, run by Assuta Medical Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 25 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact David Groshar, MD (+972-37645497, davidg@assuta.co.il), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Orientation performance (time frame: 1 day). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03030365, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2017.

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