Detecting Early Alzheimer's Using MR (DREAMER)

March 25, 2025 updated by: University of Aberdeen

Early Detection Of Alzheimer's Disease With GlucoCEST MRI: A Feasibility Study.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Target population: For the methods development phase, 20 healthy volunteers (age 18 years and above) without contra-indications to MRI will be recruited. Twenty patients with clinically diagnosed AD and 20 age-matched controls (+/- 3 years) will be recruited to test the clinical feasibility of glucoCEST.

As a feasibility study, the current work is unlikely to cover the full representative range of AD patients with diverse phenotypes. Its key purpose is to explore whether the proposed technique will show different glucose uptake between those with normal cognition and those with early AD. Further the purpose of future clinical use will be to detect AD in its early stage where clinical manifestations of AD are either subclinical or very mild. We will ensure that the sample is representative of the age range of AD patients, as well as sex balanced.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Other: 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.
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.
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.
Other: 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.
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.
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.
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.
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.
Other: 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.
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.
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.
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.
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.
Other: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PET glucose measurement
Time Frame: 2 years

Dynamic frames from FDG-PET will be summed and normalised to the cerebellum using MATLAB (MathWorks Inc., USA). Standardised uptake values (SUVs) from PET will then be calculated. Regions of interests (ROIs) will derived from normalisation to the standard Desikan Killiany atlas. Average SUV from PET will be calculated from each ROI in MATLAB.

Glucose uptake (maximum ΔS/So) with units of ratio.

Clearance (rate of decrease of ΔS/So) values with units of ratio.
2 years
CEST-MRI glucose measurement
Time Frame: 2 years

Dynamic frames from CEST MRI will be summed and normalised to the cerebellum using MATLAB (MathWorks Inc., USA). Standardised uptake values (SUVs) will be calculated in regions of interests (ROIs) derived from normalisation to the standard Desikan Killiany atlas. Average SUV from each ROI, the glucose uptake (maximum ΔS/So) and clearance (rate of decrease of ΔS/So) values from patients and controls will be calculated using MATLAB.

Glucose uptake (maximum ΔS/So) with units of ratio.

Clearance (rate of decrease of ΔS/So) values with units of ratio
2 years
Sensitivity and specificity of CEST-MRI glucose measurements
Time Frame: 2 years

A neuroradiologist blinded to the diagnosis of each participant will be asked to report the scans in a similar way to an FDG-PET scan. Sensitivity and specificity of glucoCEST to detect AD by estimating the proportion of true positives and true negatives respectively will be determined. To demonstrate the feasibility of glucoCEST in differentiating AD patients from controls, group comparisons of glucose (paired samples t-tests as implemented by SPSS) uptake values between patients and controls and of glucose clearance values between patients and controls will be performed.

Sensitivity and specificity values with units of ratio.
2 years
Repeatability of CEST-MRI glucose measurement
Time Frame: 2 years

To investigate the repeatability of MRI assessment, 10 out of 20 development phase healthy volunteers will be recruited to undergo a second repeated study assessment visit between 7 and 14 days after their first visit.

Coefficient of variation values with units of percent.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aberdeen

Collaborators

NHS Grampian

Investigators

  • Study Chair: Gordon Waiter, PhD, University of Aberdeen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2022

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

November 3, 2022

First Submitted That Met QC Criteria

November 10, 2022

First Posted (Actual)

November 14, 2022

Study Record Updates

Last Update Posted (Actual)

March 30, 2025

Last Update Submitted That Met QC Criteria

March 25, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2-001-22
  • TCS/21/03 (Other Grant/Funding Number: Chief Scientist Office)
  • 22\LO\0347 (Other Identifier: National Health Service Research Ethics Committees)
  • 308185 (Other Identifier: IRAS (Integrated Research Application System))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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