Enhancing Brain LesionsPhase 1NCT06224543
MR Image Synthesis With Low Gadobutrol Dose and AI
A Phase 1 study testing SubtleGAD and Gadobutrol in people with Enhancing Brain Lesions, run by Subtle Medical at 5 sites in United States.
Trial summary
Study 22403 is a Phase 1 / Proof of Concept exploratory investigation to assess the non-inferiority of low dose gadobutrol and SubtleGAD™, a software medical device using an Artificial Intelligence (AI) deep learning-based method to enhance the contrast signal from images acquired with low dose administration of… Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Enhancing Brain Lesions
- What is being tested?
- SubtleGAD and Gadobutrol
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 5 sitesUnited States
- Study dates
- 16 Jun 2023to 15 Aug 2025
- Phase
- Phase 1
- 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 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At the time of signing the informed consent at least 18 years of age and less than or equal to 89 years of age.
- Have known or highly suspected brain lesions referred for contrast-enhanced MRI of the CNS.
- Have an estimated glomerular filtration rate (eGFR) value ≥ 60 mL/min/1.73m^2.
- Be fully informed about the study, including provisions of the Health Insurance Portability and Accountability Act (HIPAA) as applicable, and being capable and willing to consent to participate.
Who cannot join
- Considered clinically unstable or has a concomitant/intercurrent condition that would not allow participation in the study.
- Diagnoses of multiple sclerosis or other disease process that is expected to change its enhancement pattern in the time period of the follow-up.
- Brain pathology or abnormalities that are not considered lesions.
- Any contraindication for MRI procedure or gadobutrol administration.
- Has severe cardiovascular disease.
- Is expected or is scheduled to have a change in any treatment or procedure between the two study periods that may alter image comparability.
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- Is scheduled or is likely to require a biopsy or any interventional therapeutic procedure from the first study MRI up to 24 hours after the second study MRI.
- Women currently lactating, pregnant, or planning on becoming pregnant during the study.
- Women of childbearing potential with a positive urine pregnancy test within 24 hours before either gadobutrol administration.
- Receipt of any gadolinium-based contrast agent <72 hours prior to the study MRIs.
- Participants with acute kidney injury.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
MD Anderson Cancer Center
Houston, Texas, 77030
Central Illinois Radiological Associates; OSF St. Francis Hospital Peoria
Peoria, Illinois, 61637
Mayo Clinic
Rochester, Minnesota, 55905
The Pennsylvania State University
State College, Pennsylvania, 16801
UMass Chan Medical School
Worcester, Massachusetts, 01655
About this study
Official title: Evaluate Artificial Intelligence (AI) Synthesized MR Images From Low Dose Gadobutrol CNS Images vs Standard Dose Gadobutrol CNS Images
Study 22403 is a Phase 1 / Proof of Concept exploratory investigation to assess the non-inferiority of low dose gadobutrol and SubtleGAD™, a software medical device using an Artificial Intelligence (AI) deep learning-based method to enhance the contrast signal from images acquired with low dose administration of gadobutrol (GAD) contrast. The primary objective is to demonstrate noninferiority of synthesized Central Nervous System (CNS) magnetic resonance (MR) images for 1 or 2 different gadobutrol-enhanced low-dose groups (0.01mmol/kg, and0.025 mmol/kg) compared to gadobutrol-enhanced CNS MR images at a standard dose of 0.1 mmol/kg. This investigation is a prospective, randomized, open label, multi-center study with blinded reads in participants with known or highly suspected CNS pathology. There will be at least 60 participants enrolled (30 per study arm). SubtleGAD will be used as a post-processing tool, prior to blinded read assessment of MR images acquired in either arm of the study.
- Conditions
- Enhancing Brain Lesions
- Being tested
- SubtleGAD, Gadobutrol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SubtleGADDevice
SubtleGAD is an image processing software developed to enhance MR images acquired with low dose gadobutrol.
GadobutrolDrug
Also called Gadavist Injection
Gadavist is indicated for use with magnetic resonance imaging (MRI) in adult and pediatric patients including term neonates to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system.
| Study group | Role | What they receive |
|---|---|---|
| Group A (10% dose GV) | Active comparator | Each participant will receive a Standard dose gadobutrol (0.1 mmol/kg) in Period 1 and 10% dose gadobutrol (0.01 mmol/kg) in Period 2. During study Period 1, each participant will receive gadobutrol as a single intravenous (IV) administration at the standard dose for contrast-enhanced MRI followed by study Period 2 where a single IV low dose (10% dose) of gadobutrol will be administered. There will be a washout period of at least 72 hours but less than 15 days between the two periods. The individual study duration will therefore range from 4 to 15 days. Receives: Device: SubtleGAD; Drug: Gadobutrol |
| Group B (25% dose GV) | Active comparator | Each participant will receive a Standard dose gadobutrol (0.1 mmol/kg) in Period 1 and Study Period 2: 25% dose gadobutrol (0.025 mmol/kg) in Period 2. During study Period 1, each participant will receive gadobutrol as a single intravenous (IV) administration at the standard dose for contrast-enhanced MRI followed by study Period 2 where a single IV low dose (25% dose) of gadobutrol will be administered. There will be a washout period of at least 72 hours but less than 15 days between the two periods. The individual study duration will therefore range from 4 to 15 days. Receives: Device: SubtleGAD; Drug: Gadobutrol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare enhancement of SubtleGAD in 10% dose and 25% dose gadobutrol MR images.
Compare enhancing lesions in gadobutrol-enhanced central nervous system (CNS) magnetic resonance imaging (MRI) low dose groups (0.01 mmol/kg, 0.025 mmol/kg), and standard dose (0.1 mmol/kg).
Measured: 4 to 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2024
- Study start16 Jun 2023
- Primary completion7 Jul 2025
- Study completion15 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Enhancing Brain LesionsStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two interventional groups: Group A: 0.01 mmol/kg GV, Group B: 0.025 mmol/kg GV. Both groups also receive GV standard dose (0.1 mmol/kg) that serves as the clinical image set for the participant and as comparator.
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Subtle Medical
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bayer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06224543
- Sponsor's protocol ID
- 22403
- Status last verified
- Aug 2025
- First submitted
- 16 Jan 2024
- Last updated
- 2 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluate Artificial Intelligence (AI) Synthesized MR Images From Low Dose Gadobutrol CNS Images vs Standard Dose Gadobutrol CNS Images
- ClinicalTrials.gov ID
- NCT06224543
- Acronym / sponsor ID
- 22403
- Conditions
- Enhancing Brain Lesions
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Subtle MedicalIndustry (pharma, biotech, devices)
- Collaborators
- Bayer
- Study start
- 16 Jun 2023 (actual)
- Primary completion
- 7 Jul 2025 (actual)
- Study completion
- 15 Aug 2025 (actual)
- First posted
- 25 Jan 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.
Study 22403 is a Phase 1 / Proof of Concept exploratory investigation to assess the non-inferiority of low dose gadobutrol and SubtleGAD™, a software medical device using an Artificial Intelligence (AI) deep learning-based method to enhance the contrast signal from images acquired with low dose administration of gadobutrol (GAD) contrast. The primary objective is to demonstrate noninferiority of synthesized Central Nervous System (CNS) magnetic resonance (MR) images for 1 or 2 different gadobutrol-enhanced low-dose groups (0.01mmol/kg, and0.025 mmol/kg) compared to gadobutrol-enhanced CNS MR images at a standard dose of 0.1 mmol/kg. This investigation is a prospective, randomized, open label, multi-center study with blinded reads in participants with known or highly suspected CNS pathology. There will be at least 60 participants enrolled (30 per study arm). SubtleGAD will be used as a post-processing tool, prior to blinded read assessment of MR images acquired in either arm of the study.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two interventional groups: Group A: 0.01 mmol/kg GV, Group B: 0.025 mmol/kg GV. Both groups also receive GV standard dose (0.1 mmol/kg) that serves as the clinical image set for the participant and as comparator.
| Arm | Type | Receives |
|---|---|---|
| Group A (10% dose GV) | Active comparator | Device: SubtleGAD, Drug: GadobutrolEach participant will receive a Standard dose gadobutrol (0.1 mmol/kg) in Period 1 and 10% dose gadobutrol (0.01 mmol/kg) in Period 2. During study Period 1, each participant will receive gadobutrol as a single intravenous (IV) administration at the standard dose for contrast-enhanced MRI followed by study Period 2 where a single IV low dose (10% dose) of gadobutrol will be administered. There will be a washout period of at least 72 hours but less than 15 days between the two periods. The individual study duration will therefore range from 4 to 15 days. |
| Group B (25% dose GV) | Active comparator | Device: SubtleGAD, Drug: GadobutrolEach participant will receive a Standard dose gadobutrol (0.1 mmol/kg) in Period 1 and Study Period 2: 25% dose gadobutrol (0.025 mmol/kg) in Period 2. During study Period 1, each participant will receive gadobutrol as a single intravenous (IV) administration at the standard dose for contrast-enhanced MRI followed by study Period 2 where a single IV low dose (25% dose) of gadobutrol will be administered. There will be a washout period of at least 72 hours but less than 15 days between the two periods. The individual study duration will therefore range from 4 to 15 days. |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- At the time of signing the informed consent at least 18 years of age and less than or equal to 89 years of age.
- Have known or highly suspected brain lesions referred for contrast-enhanced MRI of the CNS.
- Have an estimated glomerular filtration rate (eGFR) value ≥ 60 mL/min/1.73m^2.
- Be fully informed about the study, including provisions of the Health Insurance Portability and Accountability Act (HIPAA) as applicable, and being capable and willing to consent to participate.
Key exclusion criteria (11 listed)
- Considered clinically unstable or has a concomitant/intercurrent condition that would not allow participation in the study.
- Diagnoses of multiple sclerosis or other disease process that is expected to change its enhancement pattern in the time period of the follow-up.
- Brain pathology or abnormalities that are not considered lesions.
- Any contraindication for MRI procedure or gadobutrol administration.
- Has severe cardiovascular disease.
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 |
|---|---|---|
| SubtleGADSubtleGAD is an image processing software developed to enhance MR images acquired with low dose gadobutrol. | Device | Group A (10% dose GV), Group B (25% dose GV) |
| GadobutrolAlso: Gadavist InjectionGadavist is indicated for use with magnetic resonance imaging (MRI) in adult and pediatric patients including term neonates to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. | Drug | Group A (10% dose GV), Group B (25% dose GV) |
Primary outcome
Compare enhancement of SubtleGAD in 10% dose and 25% dose gadobutrol MR images.
Time frame: 4 to 15 days
Compare enhancing lesions in gadobutrol-enhanced central nervous system (CNS) magnetic resonance imaging (MRI) low dose groups (0.01 mmol/kg, 0.025 mmol/kg), and standard dose (0.1 mmol/kg).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2025.
- Individual participant dataSharing planned: No
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SubtleGAD and Gadobutrol in people with Enhancing Brain Lesions, run by Subtle Medical at 5 sites in United States.
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 4 inclusion and 11 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: finished, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare enhancement of SubtleGAD in 10% dose and 25% dose gadobutrol MR images. (time frame: 4 to 15 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Sep 2025.