Detecting Early Alzheimer's Using MR

NCT ID: NCT05614310

Last Updated: 2025-03-30

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

RECRUITING

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-11-15

Study Completion Date

2025-12-31

Brief Summary

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Alzheimer's disease (AD) is the most common cause of dementia, affecting approximately 10% of individuals aged ≥ 65. Most available treatments aim at controlling symptoms at an early stage rather than providing a cure. Therefore, an accurate and early diagnosis of AD with appropriate management will slow the progression of the condition. Reduced cerebral glucose levels have been observed in patients with early AD. Glucose hypometabolism can be assessed by administering a radioactive glucose analogue, 2-deoxy-2-(18F) fluoro-D-glucose (18FDG), and imaging with PET (positron emission tomography). The high cost and limited availability of PET-CT (PET - computed tomography) still hamper its general clinical application. Moreover, the use of radioactive tracers in combination with the additional ionizing radiation of CT is not suitable for repeated measurements. Therefore, currently, the provisional diagnosis of AD is still based on the combination of clinical history, neurological examination, cognitive testing over a period of time, and structural neuroimaging. This has major time and resource implications.

A radically different and highly innovative means for imaging glucose with magnetic resonance imaging (MRI) has now been established, exploiting the interaction between hydroxyl protons in glucose and the protons in water; the method is termed glucose Chemical Exchange Saturation Transfer (glucoCEST). GlucoCEST MRI is a method that has no reliance on radiolabelled glucose analogues and could become widely implemented in clinic practice. We therefore aim to investigate the potential of glucoCEST MRI in Alzheimer's disease.

Detailed Description

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Alzheimer's disease (AD) is the most common cause of dementia, affecting approximately 10% of individuals aged ≥ 65. Most available treatments aim at controlling symptoms at an early stage rather than providing a cure. Therefore, an accurate and early diagnosis of AD with appropriate management will slow the progression of the condition. Reduced cerebral glucose levels have been observed in patients with early AD. Glucose hypometabolism can be assessed by administering a radioactive glucose analogue, 2-deoxy-2-(18F) fluoro-D-glucose (18FDG), and imaging with PET (positron emission tomography). The high cost and limited availability of PET-CT (PET - computed tomography) still hamper its general clinical application. Moreover, the use of radioactive tracers in combination with the additional ionizing radiation of CT is not suitable for repeated measurements. Therefore, currently, the provisional diagnosis of AD is still based on the combination of clinical history, neurological examination, cognitive testing over a period of time, and structural neuroimaging. This has major time and resource implications.

A radically different and highly innovative means for imaging glucose with magnetic resonance imaging (MRI) has now been established, exploiting the interaction between hydroxyl protons in glucose and the protons in water; the method is termed glucose Chemical Exchange Saturation Transfer (glucoCEST). GlucoCEST MRI is a method that has no reliance on radiolabelled glucose analogues and could become widely implemented in clinic practice. We believe that glucoCEST MRI has the potential to replace FDG-PET and improve patient healthcare as part of a routine clinical pathway in very early detection of AD.

The study will include 20 healthy volunteers for developing glucoCEST in the clinical 3T MRI scanner (development phase) and 20 volunteers without AD and 20 patients with clinically diagnosed AD (clinical phase). All participants will have a 3T brain MRI scan after they receive oral glucose. The participants in the clinical phase will have a 3T brain MRI scan, a brain PET scan and they will also undertake two cognitive tests.

The glucose uptake and clearance rate in the brain will be measured from PET and MRI scans and compared between groups and imaging modalities. Sensitivity and specificity of glucoCEST to detect AD will be also calculated.

Primary Objective: To estimate the sensitivity of glucose uptake as measured by glucoCEST MRI in patients with AD compared with age and sex matched controls.

Secondary objective: To investigate if the glucose uptake as measured by glucoCEST MRI is related to the glucose uptake as measured in FDG-PET.

The main aims of the study are:

1. To determine normal uptake and clearance rates of glucose in the brain as measured by dynamic glucoCEST MRI at 3T
2. To compare glucose uptake as measured by glucoCEST MRI and FDG-PET.
3. To compare glucose uptake as measured by glucoCEST MRI in patients with AD and age and sex matched controls.

Conditions

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Alzheimer Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Development Group 1 (N = 10) (Development Phase)

Development group participants (N = 10) will undergo 1 magnetic resonance imaging (MRI) sessions. Before and after their MRI scan participants will be given a pinprick blood sugar test.

Magnetic Resonance Imaging (MRI)

Intervention Type OTHER

Participants will be asked to lie in the MRI scanner while we collect 3D T1- and T2-weighted images and a 3D FLAIR image to exclude pathology (e.g. stroke). Participants will ingest a glucose solution (75 g Dextrose) so dynamic glucoCEST images can be acquired to measure glucose uptake and clearance.

Blood Glucose Assessment

Intervention Type OTHER

A blood testing meter will be used to measure the blood sugar levels before and after the scans. Normal reading for a nondiabetic person after fasting is 70-99 mg/dl (3.9-6 mmol/L). If abnormal blood sugar levels are detected (sugar levels outside the above normal range), the participant will no longer be eligible for the study and they will be withdrawn.

Patients (N = 20) (Clinical Phase)

Patients (N = 20) will attend 2 visits up to 1 week apart. Patients will be asked to have a no-sugar diet and take no exercise for 24 hours before each visit and to avoid eating 6 hours before scan.

Visit 1: Patients will undergo a positron emission tomography (PET) assessment. Before and after their PET assessment patients will be given a pinprick blood sugar test. PET assessment:

Visit 2: Patients will undergo MRI assessment. Before and after their MRI scan patients will be given a pinprick blood sugar test. Healthy controls will complete cognitive assessments.

Magnetic Resonance Imaging (MRI)

Intervention Type OTHER

Participants will be asked to lie in the MRI scanner while we collect 3D T1- and T2-weighted images and a 3D FLAIR image to exclude pathology (e.g. stroke). Participants will ingest a glucose solution (75 g Dextrose) so dynamic glucoCEST images can be acquired to measure glucose uptake and clearance.

Blood Glucose Assessment

Intervention Type OTHER

A blood testing meter will be used to measure the blood sugar levels before and after the scans. Normal reading for a nondiabetic person after fasting is 70-99 mg/dl (3.9-6 mmol/L). If abnormal blood sugar levels are detected (sugar levels outside the above normal range), the participant will no longer be eligible for the study and they will be withdrawn.

Positron Emission Tomography (PET)

Intervention Type OTHER

Participants will be administered a radioactive glucose analogue, 2-deoxy-2-(18F) fluoro-D-glucose (18FDG) through a canula inserted into a vein in the arm or hand and asked to sit quietly for 1 h. After 1 h they will be asked to lie quietly and without talking in the PET scanner and a PET brain scan will be performed.

Cognitive Assessment

Intervention Type OTHER

Participants will be asked to undertake two cognitive tests (the Alzheimer's Disease Assessment Scale ADAS-cog test and the Mini Mental State Examination test - MMSE). These are standard clinical tests used to determine cognitive dysfunction in Alzheimer's disease.

Healthy Controls (N = 20) (Clinical Phase)

Healthy controls (N = 20) will attend 2 visits up to 1 week apart. Healthy controls will be age matched (+/- 3 years) and sex matched to the patient group. Healthy controls will be asked to have a no-sugar diet and take no exercise for 24 hours before each visit and to avoid eating 6 hours before scan.

Visit 1: Healthy Controls will undergo a positron emission tomography (PET) assessment. Before and after their PET assessment patients will be given a pinprick blood sugar test. PET assessment:

Visit 2: Healthy Controls will undergo MRI assessment. Before and after their MRI scan patients will be given a pinprick blood sugar test. Healthy controls will complete cognitive assessments.

Magnetic Resonance Imaging (MRI)

Intervention Type OTHER

Participants will be asked to lie in the MRI scanner while we collect 3D T1- and T2-weighted images and a 3D FLAIR image to exclude pathology (e.g. stroke). Participants will ingest a glucose solution (75 g Dextrose) so dynamic glucoCEST images can be acquired to measure glucose uptake and clearance.

Blood Glucose Assessment

Intervention Type OTHER

A blood testing meter will be used to measure the blood sugar levels before and after the scans. Normal reading for a nondiabetic person after fasting is 70-99 mg/dl (3.9-6 mmol/L). If abnormal blood sugar levels are detected (sugar levels outside the above normal range), the participant will no longer be eligible for the study and they will be withdrawn.

Positron Emission Tomography (PET)

Intervention Type OTHER

Participants will be administered a radioactive glucose analogue, 2-deoxy-2-(18F) fluoro-D-glucose (18FDG) through a canula inserted into a vein in the arm or hand and asked to sit quietly for 1 h. After 1 h they will be asked to lie quietly and without talking in the PET scanner and a PET brain scan will be performed.

Cognitive Assessment

Intervention Type OTHER

Participants will be asked to undertake two cognitive tests (the Alzheimer's Disease Assessment Scale ADAS-cog test and the Mini Mental State Examination test - MMSE). These are standard clinical tests used to determine cognitive dysfunction in Alzheimer's disease.

Development Group 2 (N = 10) (Development Phase)

To investigate the repeatability of MRI assessment, 10 development phase healthy volunteers will be recruited to undergo two repeated study assessments. The second visit will be between 7 and 14 days after their first visit. The second repeated study assessment will follow the same procedure as the first visit, consisting of blood glucose assessment and MRI assessment. Participants will be advised to fast from mid-night and avoid eating breakfast.

Magnetic Resonance Imaging (MRI)

Intervention Type OTHER

Participants will be asked to lie in the MRI scanner while we collect 3D T1- and T2-weighted images and a 3D FLAIR image to exclude pathology (e.g. stroke). Participants will ingest a glucose solution (75 g Dextrose) so dynamic glucoCEST images can be acquired to measure glucose uptake and clearance.

Blood Glucose Assessment

Intervention Type OTHER

A blood testing meter will be used to measure the blood sugar levels before and after the scans. Normal reading for a nondiabetic person after fasting is 70-99 mg/dl (3.9-6 mmol/L). If abnormal blood sugar levels are detected (sugar levels outside the above normal range), the participant will no longer be eligible for the study and they will be withdrawn.

Interventions

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Magnetic Resonance Imaging (MRI)

Participants will be asked to lie in the MRI scanner while we collect 3D T1- and T2-weighted images and a 3D FLAIR image to exclude pathology (e.g. stroke). Participants will ingest a glucose solution (75 g Dextrose) so dynamic glucoCEST images can be acquired to measure glucose uptake and clearance.

Intervention Type OTHER

Blood Glucose Assessment

A blood testing meter will be used to measure the blood sugar levels before and after the scans. Normal reading for a nondiabetic person after fasting is 70-99 mg/dl (3.9-6 mmol/L). If abnormal blood sugar levels are detected (sugar levels outside the above normal range), the participant will no longer be eligible for the study and they will be withdrawn.

Intervention Type OTHER

Positron Emission Tomography (PET)

Participants will be administered a radioactive glucose analogue, 2-deoxy-2-(18F) fluoro-D-glucose (18FDG) through a canula inserted into a vein in the arm or hand and asked to sit quietly for 1 h. After 1 h they will be asked to lie quietly and without talking in the PET scanner and a PET brain scan will be performed.

Intervention Type OTHER

Cognitive Assessment

Participants will be asked to undertake two cognitive tests (the Alzheimer's Disease Assessment Scale ADAS-cog test and the Mini Mental State Examination test - MMSE). These are standard clinical tests used to determine cognitive dysfunction in Alzheimer's disease.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

Development phase:

Controls (development group) must:

* be \> 18 years
* consent to the study
* not report problems with memory.

Clinical phase

Patients must:

* be ≥ 65 years,
* able to provide informed consent to the study
* have been clinically diagnosed with AD by the mental health team.

Controls must:

* be ≥ 65 years
* able to provide consent to the study
* have a normal score in the ADAS-cog test and the Mini Mental State Examination test (MMSE)
* not report problems with memory.

Exclusion Criteria

Subjects will not be considered if they:

* have a history of diabetes,
* have history of a major stroke (mini-stroke/Transient Ischaemic Attacks or lacunar stroke are acceptable),
* have contra-indications to MRI scanning such as implantable cardiac devices
* have family history in AD, to exclude possible gene mutations associated with AD
* have advanced AD who lack the capacity to consent.
* Are pregnant (for developmental phase)
* are unable to read or speak English
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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NHS Grampian

OTHER_GOV

Sponsor Role collaborator

University of Aberdeen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gordon Waiter, PhD

Role: STUDY_CHAIR

University of Aberdeen

Locations

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University of Aberdeen

Aberdeen, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Gordon Waiter, PhD

Role: CONTACT

+44 (0)1224 438356

Nicholas Senn de Vries, PhD

Role: CONTACT

+44 (0)1224 438352

Facility Contacts

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Gordon Waiter, PhD

Role: primary

+44 (0)1224 438356

Nicholas Senn de Vries, PhD

Role: backup

+44 (0)1224 438352

References

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Kukull WA, Higdon R, Bowen JD, McCormick WC, Teri L, Schellenberg GD, van Belle G, Jolley L, Larson EB. Dementia and Alzheimer disease incidence: a prospective cohort study. Arch Neurol. 2002 Nov;59(11):1737-46. doi: 10.1001/archneur.59.11.1737.

Reference Type BACKGROUND
PMID: 12433261 (View on PubMed)

Bloudek LM, Spackman DE, Blankenburg M, Sullivan SD. Review and meta-analysis of biomarkers and diagnostic imaging in Alzheimer's disease. J Alzheimers Dis. 2011;26(4):627-45. doi: 10.3233/JAD-2011-110458.

Reference Type BACKGROUND
PMID: 21694448 (View on PubMed)

Marcus C, Mena E, Subramaniam RM. Brain PET in the diagnosis of Alzheimer's disease. Clin Nucl Med. 2014 Oct;39(10):e413-22; quiz e423-6. doi: 10.1097/RLU.0000000000000547.

Reference Type BACKGROUND
PMID: 25199063 (View on PubMed)

Tolomeo D, Micotti E, Serra SC, Chappell M, Snellman A, Forloni G. Chemical exchange saturation transfer MRI shows low cerebral 2-deoxy-D-glucose uptake in a model of Alzheimer's Disease. Sci Rep. 2018 Jun 22;8(1):9576. doi: 10.1038/s41598-018-27839-7.

Reference Type BACKGROUND
PMID: 29934551 (View on PubMed)

Wang J, Weygand J, Hwang KP, Mohamed AS, Ding Y, Fuller CD, Lai SY, Frank SJ, Zhou J. Magnetic Resonance Imaging of Glucose Uptake and Metabolism in Patients with Head and Neck Cancer. Sci Rep. 2016 Jul 27;6:30618. doi: 10.1038/srep30618.

Reference Type BACKGROUND
PMID: 27461165 (View on PubMed)

Kim M, Torrealdea F, Adeleke S, Rega M, Evans V, Beeston T, Soteriou K, Thust S, Kujawa A, Okuchi S, Isaac E, Piga W, Lambert JR, Afaq A, Demetriou E, Choudhary P, Cheung KK, Naik S, Atkinson D, Punwani S, Golay X. Challenges in glucoCEST MR body imaging at 3 Tesla. Quant Imaging Med Surg. 2019 Oct;9(10):1628-1640. doi: 10.21037/qims.2019.10.05.

Reference Type BACKGROUND
PMID: 31728307 (View on PubMed)

Other Identifiers

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TCS/21/03

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

22\LO\0347

Identifier Type: OTHER

Identifier Source: secondary_id

308185

Identifier Type: OTHER

Identifier Source: secondary_id

2-001-22

Identifier Type: -

Identifier Source: org_study_id

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