AgingSIGNATURES2023NCT06705010
Monitoring of Brain Metabolites Using Proton and Deuterium MR Techniques
A study testing Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot) in people with Aging and Brain Metabolic Disorder, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
MR pulse for whole brain optimal Deuterium (2H) Metabolic Imaging and EPSI (echo planar spectroscopic imaging) based SLOW-edited 1H-MRSI will be developed and optimized for use at an UHF scanner at 7 Tesla. The study has 4 phases. Read more about this study
- Who is it for?
- Ages 18 to 130 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging, Brain Metabolic Disorder, Carotid Stenosis
- What is being tested?
- Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Apr 2025to 31 Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 130 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Under 18 years of age.
- Claustrophobia.
- Pregnancy or current state of lactation.
- Active implants (e.g., pacemakers, neuro-stimulators).
- Passive ferromagnetic implants.
- Passive non-ferromagnetic metallic implants > 4 cm in a region covered by the active radio frequency (RF) coils.
Show all 44Show fewer
- Large tattoos inside a region covered by the active RF coils.
- Known or suspected non-compliance.
- Underweight <30 kg body weight.
- Body mass index (BMI) > 30.
- Overweight >135 kg
- Persons with extreme big head circumference or extreme astigmatism, which cannot be corrected by MR-compatible eyeglasses.
- Persons not able to understand the informed consent form.
- Not agreeing with the institute's policy to inform the subject on incidental findings discovered during the examination.
- Visual and auditory acuity impairing neuropsychological testing (if relevant).
- Diabetes or glucose intolerance according to WHO recommendations (excluded in the diabetes patient group).
- Evidence of overt heart or renal disease.
- Evidence of gastrointestinal tract disease.
- Cognitive impairment (Mini-mental state examination score <26/30, CDR score >0, memory complaints) (excluding AD, MCI groups).
- Smoking.
- Current or life-time drug or alcohol abuse
- Untreated dyslipidemia, hypertension, or thyroid disease.
- Antidepressant medications with anticholinergic properties.
- Regular use of narcotic agents more than two doses per week within 4 weeks of screening.
- Antiparkinsonian medications used within 4 weeks of screening.
- Enrollment in any investigational drug studies within 4 weeks of screening.
- Immunomodulating or oncological treatment.
- Cardiac implantable electronic devices (CIED) such as pacemakers, implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices.
- Metallic intraocular foreign bodies: patients who have ever welded without eye protection or had facial injuries involving metal must have an orbit x-ray reviewed by a radiologist before MRI.
- Implantable neurostimulation systems.
- Cochlear implants/ear implants.
- Drug infusion pumps (insulin delivery, analgesic drugs, or chemotherapy pumps).
- Catheters with metallic components (e.g., Swan-Ganz catheter).
- Metallic fragments (e.g., bullets, shotgun pellets, shrapnel).
- Cerebral artery aneurysm clips.
- Magnetic dental implants.
- Tissue expanders.
- Artificial limbs.
- Non-removable hearing aids.
- Non-removable piercings.
- Implantable cardiocerter defibrillators
- Cardiac resynchronization therapy devices
- Fever (temperature > 37.5°C measured prior to MRI).
- Volunteers taking amphetamines or sedatives
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site
Translational Imaging Center / Sitem
Bern, 3010
Johannes Johannes, Professor, +41316327469, johannes.slotboom@insel.ch
Piotr Radojewski, MD, +41316641467, piotr.radojewski@insel.ch
About this study
Official title: Non-Invasive Monitoring of Brain Metabolites Using Novel and Adapted Proton and Deuterium MR Techniques
MR pulse for whole brain optimal Deuterium (2H) Metabolic Imaging and EPSI (echo planar spectroscopic imaging) based SLOW-edited 1H-MRSI will be developed and optimized for use at an UHF scanner at 7 Tesla. The study has 4 phases.
Phase I: The 2H and 1H MRSI sequences are developed and optimized in vitro (phantoms)
Read more
Phase II: Sequences are applied in vivo in healthy volunteers and further optimized
Phase III: Optimal 2H 1H pulse sequences are applied in 4 cohorts of healthy volunteers, to study the effect of aging with whole brain 2H and 1H MRSI.
Phase IV: application of the sequences in 4 patient groups with different diseases: Alzheimer's diseases (AD) patients, diabetes mellitus type II (DM) patients, mild cognitive impaired (MCI) patients, and high grade carotid stenosis patients (HGCS).
The ultimate aim is to create for individual patient specific 3dimensional spatial resolved z-score maps (similar to FDG-PET) based on the healthy control data of phase III of the trial.
Read the detailed description
Introduction - Aging of the world's population is being increasingly recognized as a crucial societal challenge. Yet, tools to perform high-quality metabolic research on aging of the brain are very limited.
The proposed study will focus on methods to assess metabolic brain changes that occur during aging as well as in 10 patients with Alzheimer's disease (AD). Apart from AD, also 10 patients with minimal cognitive impairment (MCI), 10 patient with diabetes mellitus type 2 (DM), and 10 patients with high grade carotid stenosis will be examined.
The currently most prominent clinical method to study brain metabolism in vivo, is Positron Emission Tomography (PET) using 18F-fluorodeoxyglucose (FDG). A major drawback of this method is the ionizing radiation. A magnetic resonance spectroscopic imaging (MRSI) based method, called deuterium metabolic imaging (DMI) expands the MRSI capabilities offered by proton-based techniques and enables in vivo glucose metabolism imaging without ionizing radiation. A unique feature of DMI is that, unlike PET, it not only maps glucose uptake but also downstream products such as lactate, glutamate and glutamine thereby offering the possibility to detect metabolic disturbances associated with aging and neurodegeneration.
Due to the relatively low sensitivity of DMI, strong magnetic fields are required to increase the signal to noise ratio (SNR) and enable DMI. Recently the first commercially available Ultra High Field (UHF) 7T MR-scanner was approved for clinical use and is now available in Bern, making DMI accessible. The investigators' motivation is to provide non-invasive, radiation free, deuterium and proton based MRSI methods enabling metabolic studies of the brain and lay the foundation for long-term longitudinal observational studies of aging; something that can hardly be done with PET due to the radiation burden for healthy controls.
Objectives - The primary goal of the proposed project is to establish 3D spatially resolved deuterium (2H) and proton (1H) based MRSI methodology for studies of brain metabolism and apply this methodology in an in vivo feasibility study. To complement DMI, the investigators will establish UHF 3D-resolved spectral-edited 1H-MRSI mapping for glucose, gamma-Aminobutyric acid (GABA) and glutamate using the investigators' recently developed technique called SLOW.
The secondary goal is to create 3D spatially resolved reference atlas of metabolic information of the brain for healthy individuals.The atlas will allow spatially resolved analysis of metabolic information of individual patients having neurological disorders by comparing them to a normative data using z-score derived abnormality maps.
Hypotheses - (a.) 3D-MRSI based glucose/glutamate/lactate mapping using DMI facilitates spatially resolved quantitative comparisons between AD patients and healthy controls using z-score maps; (b.) 1H-SLOW-edited MRSI of glucose/GABA and glutamate facilitates spatially resolved quantitative comparisons between AD patients and healthy controls using z-score maps.
Methods - the investigators will (i.) adapt their UHF 1H-EPSI MRSI sequence for DMI; (ii.) optimize their 1H-SLOW-edited EPSI sequence aiming at whole brain measurement of GABA, glutamate and glucose editing, together with the metabolites N-acetyl-aspartate (NAA), choline, creatine, and aspartate; (iii.) extend their spectrIm-QMRS analytic tool to quantify and analyze 3D-2H-metabolic datasets, (iv.) compute all 3D-resolved 1H- and 2H-MRSI metabolic maps and co-register with high resolution 3D-anatomical images; (v.) develop methodology to generate metabolic atlas of normative data and perform z-score based comparisons using the atlas.
Significance - It is likely that the trend to higher field strength in MRI will continue making DMI increasingly available for research and clinical applications. UHF DMI and 1H-EPSI MRSI will provide a non-invasive way to quantify brain metabolism. DMI offers information on glucose metabolism, whereas 1H-SLOW on glucose, GABA- and glutamate-concentrations. The proposed approach to MRSI data analysis is fundamentally different from the one currently applied in clinical MRSI and would allow to detect and display even subtle variations from normative metabolic characteristic. If successful, UHF metabolic imaging would offer a radiation free modality, which could be repeatedly applied in young and healthy subjects to study aging. Importantly, the proposed methods will provide deeper insights into bioenergetics, specifically mitochondrial function, oxidative phosphorylation and use of alternative fuels for brain energy provision, information that FDG-PET cannot provide. Moreover, comparative analyses utilizing normative datasets would facilitate studies of the broad spectrum of disorders with impaired brain bioenergetics for example neurodegeneration, neuroinflammation but also diseases not specific to the central nervous systems like obesity and diabetes, all having a high socio-economic impact.
- Conditions
- Aging, Brain Metabolic Disorder, Carotid Stenosis, Alzheimer Disease, Diabetes Type 2, Mild Cognitive Impairment
- Being tested
- Application of new pulse sequence package SIGNATURES2023 to healthy controls, Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot)
- Medical subject headings
- Brain Diseases, Metabolic, Carotid Stenosis, Alzheimer Disease, Diabetes Mellitus, Type 2, Cognitive Dysfunction, Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Application of new pulse sequence package SIGNATURES2023 to healthy controlsDevice
One or more novel or further optimized non CE-marked pulse MRSI sequence is/are applied to 100 healthy subjects to determined reference metabolite maps of the whole brain
Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot)Device
One or more novel or further optimized non CE-marked pulse MRSI sequence is/are applied to 4 time 10 patients with AD, MCI, DM and HGCS to determine metabolite maps of the whole brain.
| Study group | Role | What they receive |
|---|---|---|
| Application of novel MRSI pulse sequences to healthy persons | Active comparator | Optimized MR-pulse sequences are applied to three healthy person groups after glucose solution ingestion to obtain healthy control 3D metabolic reference data. Receives: Device: Application of new pulse sequence package SIGNATURES2023 to healthy controls |
| Application of novel MRSI pulse sequences to four patient groups | Experimental | Optimized MR-pulse sequences are applied to four groups of 10 patients after glucose solution ingestion followed by patient level comparison of patient 3D metabolic data to healthy control data by z-score mapping. Receives: Device: Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot) |
What is being measured
The primary outcome is the main question the study is designed to answer.
3D spatial resolved Deuterium metabolite imaging (DMI)
Coregistered deuterium metabolite distributions (glucose, glutamate) is measured in a young healthy control group of 20 person (<40 years) is obtained, as well as coregistered deuterium metabolic images of metabolite distribution in a elder healthy control group of 20 person (>40 years) is obtained.
Measured: 36 months
3D spatial resolved SLOW-EPSI MRSI metabolite mapping
Coregistered neuro-metabolite distributions (e.g. GABA, glutamate) distribution in a young healthy control group of 20 persons (age < 40 years) are measured, as well as coregistered neuro-metabolite distributions (e.g. GABA, glutamate, ..) are measured in healthy control group of 20 persons (age > 40 years).
Measured: 36 months
3D spatial resolved 3D DMI and 3D SLOW-EPSI MRSI mapping in Alzheimer's disease (AD) patient group
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in an Alzheimer's disease (AD) patient group of 10 persons are obtained.
Measured: 48 months
3D spatial resolved 3D DMI and 3D SLOW-EPSI MRSI mapping in Mild Cognitive Impairment (MCI) patient group
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Mild Cognitive Impairment (MCI) patient group of 10 persons are obtained.
Measured: 48 months
3D DMI and 3D SLOW-EPSI MRSI mapping in a Diabetes Mellitus (DM) Type II patient group
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Diabetes Mellitus (DM) Type II patient group of 10 persons is obtained
Measured: 48 months
3D DMI and 3D SLOW-EPSI MRSI mapping in a High Grade Carotid Stenosis (HGCS) patient group
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Diabetes Mellitus (DM) Type II patient group of 10 persons is obtained
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2024
- Study start1 Apr 2025 (estimated)
- Primary completion1 Nov 2026 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 2H-MRSI and 1H-MRSI pulse sequences will be developed and protocols optimized in vitro. Suitable MR-protocols will be further optimized in vivo. These DMI-MRSI protocols will be applied after 1H/2H-glucose supplementation: 1. in a group of 20 healthy persons younger that 40 years old after deuterated glucose intake 2. in a group of 20 healthy person elder 40 years old after deuterated glucose intake 3. in a group of 10 young healthy persons to measure task based functional 2H-MRSI response. 4. in a group of 10 Alzheimer's disease patients after deuterated glucose intake 5. in a group of 10 mild cognitive impairment patients after deuterated glucose intake 6. in a group of 10 diabetes mellitus patients after deuterated glucose intake 7. in a group of 10 high grade carotid stenosis patients after alpha-D-glucose intake
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Johannes Slotboom, PhD, Principal investigator, University Hospital / Inselspital /University Bern / 3010 Bern / Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06705010
- Sponsor's protocol ID
- 2023-D0060
- Other IDs
- SNCTP000006108
- Acronym
- SIGNATURES2023
- Status last verified
- Mar 2025
- First submitted
- 21 Nov 2024
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: One raw 1H-MRSI dataset for one patient is about 25Gb large, and direct sharing will be difficult. Therefore; the data will be shared upon request.
Publications
Weng G, Radojewski P, Sheriff S, Kiefer C, Schucht P, Wiest R, Maudsley AA, Slotboom J. SLOW: A novel spectral editing method for whole-brain MRSI at ultra high magnetic field. Magn Reson Med. 2022 Jul;88(1):53-70. doi: 10.1002/mrm.29220. Epub 2022 Mar 28.
PubMed 35344608Weng G, Ermis E, Maragkou T, Krcek R, Reinhardt P, Zubak I, Schucht P, Wiest R, Slotboom J, Radojewski P. Accurate prediction of isocitrate dehydrogenase -mutation status of gliomas using SLOW-editing magnetic resonance spectroscopic imaging at 7 T MR. Neurooncol Adv. 2023 Jan 3;5(1):vdad001. doi: 10.1093/noajnl/vdad001. eCollection 2023 Jan-Dec.
PubMed 36875625Weng G, Slotboom J, Schucht P, Ermis E, Wiest R, Kloppel S, Peter J, Zubak I, Radojewski P. Simultaneous multi-region detection of GABA+ and Glx using 3D spatially resolved SLOW-editing and EPSI-readout at 7T. Neuroimage. 2024 Feb 1;286:120511. doi: 10.1016/j.neuroimage.2024.120511. Epub 2024 Jan 5.
PubMed 38184158Rakic M, Turco F, Weng G, Maes F, Sima DM, Slotboom J. Deep learning pipeline for quality filtering of MRSI spectra. NMR Biomed. 2024 Jul;37(7):e5012. doi: 10.1002/nbm.5012. Epub 2023 Jul 30.
PubMed 37518942
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Invasive Monitoring of Brain Metabolites Using Novel and Adapted Proton and Deuterium MR Techniques
- ClinicalTrials.gov ID
- NCT06705010
- Acronym / sponsor ID
- SIGNATURES2023 / 2023-D0060
- Conditions
- Aging, Brain Metabolic Disorder, Carotid Stenosis, Alzheimer Disease, Diabetes Type 2, Mild Cognitive Impairment
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 1 Apr 2025 (estimated)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 26 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
MR pulse for whole brain optimal Deuterium (2H) Metabolic Imaging and EPSI (echo planar spectroscopic imaging) based SLOW-edited 1H-MRSI will be developed and optimized for use at an UHF scanner at 7 Tesla. The study has 4 phases.
Phase I: The 2H and 1H MRSI sequences are developed and optimized in vitro (phantoms)
Phase II: Sequences are applied in vivo in healthy volunteers and further optimized
Phase III: Optimal 2H 1H pulse sequences are applied in 4 cohorts of healthy volunteers, to study the effect of aging with whole brain 2H and 1H MRSI.
Phase IV: application of the sequences in 4 patient groups with different diseases: Alzheimer's diseases (AD) patients, diabetes mellitus type II (DM) patients, mild cognitive impaired (MCI) patients, and high grade carotid stenosis patients (HGCS).
The ultimate aim is to create for individual patient specific 3dimensional spatial resolved z-score maps (similar to FDG-PET) based on the healthy control data of phase III of the trial.
Detailed description
Introduction - Aging of the world's population is being increasingly recognized as a crucial societal challenge. Yet, tools to perform high-quality metabolic research on aging of the brain are very limited.
The proposed study will focus on methods to assess metabolic brain changes that occur during aging as well as in 10 patients with Alzheimer's disease (AD). Apart from AD, also 10 patients with minimal cognitive impairment (MCI), 10 patient with diabetes mellitus type 2 (DM), and 10 patients with high grade carotid stenosis will be examined.
The currently most prominent clinical method to study brain metabolism in vivo, is Positron Emission Tomography (PET) using 18F-fluorodeoxyglucose (FDG). A major drawback of this method is the ionizing radiation. A magnetic resonance spectroscopic imaging (MRSI) based method, called deuterium metabolic imaging (DMI) expands the MRSI capabilities offered by proton-based techniques and enables in vivo glucose metabolism imaging without ionizing radiation. A unique feature of DMI is that, unlike PET, it not only maps glucose uptake but also downstream products such as lactate, glutamate and glutamine thereby offering the possibility to detect metabolic disturbances associated with aging and neurodegeneration.
Due to the relatively low sensitivity of DMI, strong magnetic fields are required to increase the signal to noise ratio (SNR) and enable DMI. Recently the first commercially available Ultra High Field (UHF) 7T MR-scanner was approved for clinical use and is now available in Bern, making DMI accessible. The investigators' motivation is to provide non-invasive, radiation free, deuterium and proton based MRSI methods enabling metabolic studies of the brain and lay the foundation for long-term longitudinal observational studies of aging; something that can hardly be done with PET due to the radiation burden for healthy controls.
Objectives - The primary goal of the proposed project is to establish 3D spatially resolved deuterium (2H) and proton (1H) based MRSI methodology for studies of brain metabolism and apply this methodology in an in vivo feasibility study. To complement DMI, the investigators will establish UHF 3D-resolved spectral-edited 1H-MRSI mapping for glucose, gamma-Aminobutyric acid (GABA) and glutamate using the investigators' recently developed technique called SLOW.
The secondary goal is to create 3D spatially resolved reference atlas of metabolic information of the brain for healthy individuals.The atlas will allow spatially resolved analysis of metabolic information of individual patients having neurological disorders by comparing them to a normative data using z-score derived abnormality maps.
Hypotheses - (a.) 3D-MRSI based glucose/glutamate/lactate mapping using DMI facilitates spatially resolved quantitative comparisons between AD patients and healthy controls using z-score maps; (b.) 1H-SLOW-edited MRSI of glucose/GABA and glutamate facilitates spatially resolved quantitative comparisons between AD patients and healthy controls using z-score maps.
Methods - the investigators will (i.) adapt their UHF 1H-EPSI MRSI sequence for DMI; (ii.) optimize their 1H-SLOW-edited EPSI sequence aiming at whole brain measurement of GABA, glutamate and glucose editing, together with the metabolites N-acetyl-aspartate (NAA), choline, creatine, and aspartate; (iii.) extend their spectrIm-QMRS analytic tool to quantify and analyze 3D-2H-metabolic datasets, (iv.) compute all 3D-resolved 1H- and 2H-MRSI metabolic maps and co-register with high resolution 3D-anatomical images; (v.) develop methodology to generate metabolic atlas of normative data and perform z-score based comparisons using the atlas.
Significance - It is likely that the trend to higher field strength in MRI will continue making DMI increasingly available for research and clinical applications. UHF DMI and 1H-EPSI MRSI will provide a non-invasive way to quantify brain metabolism. DMI offers information on glucose metabolism, whereas 1H-SLOW on glucose, GABA- and glutamate-concentrations. The proposed approach to MRSI data analysis is fundamentally different from the one currently applied in clinical MRSI and would allow to detect and display even subtle variations from normative metabolic characteristic. If successful, UHF metabolic imaging would offer a radiation free modality, which could be repeatedly applied in young and healthy subjects to study aging. Importantly, the proposed methods will provide deeper insights into bioenergetics, specifically mitochondrial function, oxidative phosphorylation and use of alternative fuels for brain energy provision, information that FDG-PET cannot provide. Moreover, comparative analyses utilizing normative datasets would facilitate studies of the broad spectrum of disorders with impaired brain bioenergetics for example neurodegeneration, neuroinflammation but also diseases not specific to the central nervous systems like obesity and diabetes, all having a high socio-economic impact.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 2H-MRSI and 1H-MRSI pulse sequences will be developed and protocols optimized in vitro. Suitable MR-protocols will be further optimized in vivo. These DMI-MRSI protocols will be applied after 1H/2H-glucose supplementation: 1. in a group of 20 healthy persons younger that 40 years old after deuterated glucose intake 2. in a group of 20 healthy person elder 40 years old after deuterated glucose intake 3. in a group of 10 young healthy persons to measure task based functional 2H-MRSI response. 4. in a group of 10 Alzheimer's disease patients after deuterated glucose intake 5. in a group of 10 mild cognitive impairment patients after deuterated glucose intake 6. in a group of 10 diabetes mellitus patients after deuterated glucose intake 7. in a group of 10 high grade carotid stenosis patients after alpha-D-glucose intake
| Arm | Type | Receives |
|---|---|---|
| Application of novel MRSI pulse sequences to healthy persons | Active comparator | Device: Application of new pulse sequence package SIGNATURES2023 to healthy controlsOptimized MR-pulse sequences are applied to three healthy person groups after glucose solution ingestion to obtain healthy control 3D metabolic reference data. |
| Application of novel MRSI pulse sequences to four patient groups | Experimental | Device: Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot)Optimized MR-pulse sequences are applied to four groups of 10 patients after glucose solution ingestion followed by patient level comparison of patient 3D metabolic data to healthy control data by z-score mapping. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (44 listed)
- Under 18 years of age.
- Claustrophobia.
- Pregnancy or current state of lactation.
- Active implants (e.g., pacemakers, neuro-stimulators).
- Passive ferromagnetic implants.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Application of new pulse sequence package SIGNATURES2023 to healthy controlsOne or more novel or further optimized non CE-marked pulse MRSI sequence is/are applied to 100 healthy subjects to determined reference metabolite maps of the whole brain | Device | Application of novel MRSI pulse sequences to healthy persons |
| Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot)One or more novel or further optimized non CE-marked pulse MRSI sequence is/are applied to 4 time 10 patients with AD, MCI, DM and HGCS to determine metabolite maps of the whole brain. | Device | Application of novel MRSI pulse sequences to four patient groups |
Primary outcome
3D spatial resolved Deuterium metabolite imaging (DMI)
Time frame: 36 months
Coregistered deuterium metabolite distributions (glucose, glutamate) is measured in a young healthy control group of 20 person (<40 years) is obtained, as well as coregistered deuterium metabolic images of metabolite distribution in a elder healthy control group of 20 person (>40 years) is obtained.
3D spatial resolved SLOW-EPSI MRSI metabolite mapping
Time frame: 36 months
Coregistered neuro-metabolite distributions (e.g. GABA, glutamate) distribution in a young healthy control group of 20 persons (age < 40 years) are measured, as well as coregistered neuro-metabolite distributions (e.g. GABA, glutamate, ..) are measured in healthy control group of 20 persons (age > 40 years).
3D spatial resolved 3D DMI and 3D SLOW-EPSI MRSI mapping in Alzheimer's disease (AD) patient group
Time frame: 48 months
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in an Alzheimer's disease (AD) patient group of 10 persons are obtained.
3D spatial resolved 3D DMI and 3D SLOW-EPSI MRSI mapping in Mild Cognitive Impairment (MCI) patient group
Time frame: 48 months
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Mild Cognitive Impairment (MCI) patient group of 10 persons are obtained.
3D DMI and 3D SLOW-EPSI MRSI mapping in a Diabetes Mellitus (DM) Type II patient group
Time frame: 48 months
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Diabetes Mellitus (DM) Type II patient group of 10 persons is obtained
3D DMI and 3D SLOW-EPSI MRSI mapping in a High Grade Carotid Stenosis (HGCS) patient group
Time frame: 48 months
Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Diabetes Mellitus (DM) Type II patient group of 10 persons is obtained
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
- Background: PubMed 35344608Weng G, Radojewski P, Sheriff S, Kiefer C, Schucht P, Wiest R, Maudsley AA, Slotboom J. SLOW: A novel spectral editing method for whole-brain MRSI at ultra high magnetic field. Magn Reson Med. 2022 Jul;88(1):53-70. doi: 10.1002/mrm.29220. Epub 2022 Mar 28.
- Background: PubMed 36875625Weng G, Ermis E, Maragkou T, Krcek R, Reinhardt P, Zubak I, Schucht P, Wiest R, Slotboom J, Radojewski P. Accurate prediction of isocitrate dehydrogenase -mutation status of gliomas using SLOW-editing magnetic resonance spectroscopic imaging at 7 T MR. Neurooncol Adv. 2023 Jan 3;5(1):vdad001. doi: 10.1093/noajnl/vdad001. eCollection 2023 Jan-Dec.
- Background: PubMed 38184158Weng G, Slotboom J, Schucht P, Ermis E, Wiest R, Kloppel S, Peter J, Zubak I, Radojewski P. Simultaneous multi-region detection of GABA+ and Glx using 3D spatially resolved SLOW-editing and EPSI-readout at 7T. Neuroimage. 2024 Feb 1;286:120511. doi: 10.1016/j.neuroimage.2024.120511. Epub 2024 Jan 5.
- Background: PubMed 37518942Rakic M, Turco F, Weng G, Maes F, Sima DM, Slotboom J. Deep learning pipeline for quality filtering of MRSI spectra. NMR Biomed. 2024 Jul;37(7):e5012. doi: 10.1002/nbm.5012. Epub 2023 Jul 30.
- Website where a description of a MRSI processing tool is described and can be downloadedLink provided by the sponsor.
- Individual participant dataSharing planned: No. One raw 1H-MRSI dataset for one patient is about 25Gb large, and direct sharing will be difficult. Therefore; the data will be shared upon request.
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Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
Multiple Sclerosis
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Validation & Intervention Testing for Aging, Longevity and Healthspan
Aging, Functional Decline
RecruitingObservational study
Effects of Obesity on Physical Abilities and Daily Living Activities in Elderly Adults
Obesity, Sarcopenic Obesity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Johannes Slotboom, PhD principal investigator
University Hospital / Inselspital /University Bern / 3010 Bern / Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot) in people with Aging and Brain Metabolic Disorder, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 0 inclusion and 44 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: opening soon, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Johannes Slotboom, PhD (+41316327469, johannes.slotboom@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3D spatial resolved Deuterium metabolite imaging (DMI) (time frame: 36 months). The study lists 6 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 NCT06705010, which also lists 4 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 Mar 2025.