MR Image Synthesis With Low Gadobutrol Dose and AI

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.

Study Overview

• Status: Completed
• Conditions: Enhancing Brain Lesions
• Intervention / Treatment: Device: SubtleGAD; Drug: Gadobutrol

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Peoria, Illinois, United States, 61637
      • Central Illinois Radiological Associates; OSF St. Francis Hospital Peoria
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Chan Medical School
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Pennsylvania
    • State College, Pennsylvania, United States, 16801
      • The Pennsylvania State University
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At the time of signing the informed consent at least 18 years of age and less than or equal to 89 years of age.
2. Have known or highly suspected brain lesions referred for contrast-enhanced MRI of the CNS.
3. Have an estimated glomerular filtration rate (eGFR) value ≥ 60 mL/min/1.73m^2.
4. 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.

Exclusion Criteria:

1. Considered clinically unstable or has a concomitant/intercurrent condition that would not allow participation in the study.
2. Diagnoses of multiple sclerosis or other disease process that is expected to change its enhancement pattern in the time period of the follow-up.
3. Brain pathology or abnormalities that are not considered lesions.
4. Any contraindication for MRI procedure or gadobutrol administration.
5. Has severe cardiovascular disease.
6. Is expected or is scheduled to have a change in any treatment or procedure between the two study periods that may alter image comparability.
7. 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.
8. Women currently lactating, pregnant, or planning on becoming pregnant during the study.
9. Women of childbearing potential with a positive urine pregnancy test within 24 hours before either gadobutrol administration.
10. Receipt of any gadolinium-based contrast agent <72 hours prior to the study MRIs.
11. Participants with acute kidney injury.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A (10% dose GV); 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.	Device: SubtleGAD; SubtleGAD is an image processing software developed to enhance MR images acquired with low dose gadobutrol.; Drug: Gadobutrol; 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.; Other Names: Gadavist Injection
Active Comparator: Group B (25% dose GV); 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.	Device: SubtleGAD; SubtleGAD is an image processing software developed to enhance MR images acquired with low dose gadobutrol.; Drug: Gadobutrol; 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.; Other Names: Gadavist Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	4 to 15 days

Collaborators and Investigators

• Sponsor: Subtle Medical
• Collaborators: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2023
• Primary Completion (Actual): July 7, 2025
• Study Completion (Actual): August 15, 2025

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: gadobutrol
• Other Study ID Numbers: 22403

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: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No