A Phase 1 interventional study of Gadobutrol in Healthy Volunteers, sponsored by National Institute of Neurological Disorders and Stroke (NINDS). Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-11-13.
Sponsored by National Institute of Neurological Disorders and Stroke (NINDS) · Phase 1, Interventional, and Other
Help build ClinicalTrials.gg — short surveys, remote interviews or testing, in your language. Take part →
Background:
Cerebrospinal fluid (CSF) is the liquid that fills the space around the brain and spinal cord. Researchers do not fully understand how CSF flows and drains around the brain. They want to test a tracer (gadobutrol)-a special dye injected into the CSF-to find out if it is safe to use and can help them get clearer pictures of the CSF during magnetic resonance imaging (MRI) scans of the brain.
Objective:
To test gadobutrol in the CSF during MRI scans of healthy people.
Eligibility:
Healthy volunteers aged 18 years and older. They must be screened under NIH protocol 89N0045.
Design:
Participants will check into the clinic for a 3-day stay.
They will have a lumbar puncture: An area on their lower back will be numbed. A thin needle will be inserted into the space around the spinal cord. A sample of CSF will be taken for research. Then a low dose of gadobutrol will be injected into the CSF.
Participants will have 4 or 5 MRI scans of the brain-30 minutes, 4 hours, 8 hours (this one is optional), 24 hours, and 48 hours after receiving the gadobutrol.
For the scan, they will lie on a table that slides into a cylinder. Special padding will be used to hold their head still. The MRI uses magnetic fields to create images of the inside of the body. Blood and urine samples will also be collected at each scan.
Participants will return for an additional MRI 1 week after they leave the clinic. They will have 2 follow-up phone calls 4 and 12 weeks after the start of the study.
Study Description:
In this study, we will gather safety data on and establish the technical feasibility of bypassing the blood-brain-barrier (BBB) with intrathecal (IT) gadolinium-based contrast agent (GBCA) tracer injection (0.25 ml gadobutrol at a concentration of 1.0 mmol/ml) to dynamically image the subarachnoid space (SAS) in human healthy volunteers. We will also obtain preliminary data on whether this approach will enable us to reliably visualize physiological meningeal lymphatic drainage pathways within the parasagittal dura (PSD) and connections to cerebrospinal fluid (CSF) compartments using serial contrast-enhanced magnetic resonance imaging (CE-MRI) with minimal confounding signal from tracer blood egress. In exploratory analysis, we will quantify temporal clearance kinetics and investigate distribution patterns of GBCA enhancement in the PSD, CSF spaces, and brain parenchyma in up to 12 healthy volunteers using repeated in vivo CE-MRI over 10 days. Safety/tolerability of the IT GBCA administration will be assessed descriptively over the entire 12-week study period.
Objectives:
Primary objective: To track safety/tolerability of IT GBCA administration in healthy human volunteers.
Secondary objective: To establish technical feasibility of dynamic subarachnoid-space imaging using IT GBCA administration in healthy human volunteers.
Exploratory objectives: To explore patterns of dynamic meningeal lymphatic clearance pathway interconnections in vivo under physiological conditions in human healthy volunteers, and to obtain preliminary data regarding the effect of aging on CSF dynamics and CSF-to-blood tracer clearance.
Endpoints:
Primary endpoint: Occurrence of intervention-emergent adverse events at the participant level assessed descriptively over the 12-week study period.
Secondary outcome measure: MRI detection status (yes/no) of contrast in the cerebral SAS at 24 hours.
Exploratory outcome measures: Changes in contrast-to-noise ratio (CNR) and clearance kinetics of SAS to brain parenchyma over 48h.
National Institute of Neurological Disorders and Stroke (NINDS) is the lead sponsor of 601 studies on the registry; 56 are open to participants now.
Of its 18 completed or terminated interventional studies of FDA-regulated products, 8 (44%) have results posted.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Oct 28, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
To be eligible to participate in this study, an individual must meet all the following criteria:
To explore age-related effects on tracer dynamics and clearance, 3 cohorts of participants will be recruited: 1) 18-30 years, 2) 30-55 years, and 3) >55 years; with 2 males and 2 females in each age group.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
0.25 mmol IT gadobutrol or 0.5 mmol
Drug: Gadobutrol
contrast agent
Occurrence of intervention-emergent adverse events at the participant level assessed descriptively
Systematic recording of adverse events is essential to determine the safety of IT gadobutrol, especially given its off-label use in healthy volunteers. With the limited sample size of this Phase 1 study, safety assessment is appropriately based on a descriptive evaluation rather than formal hypothesis testing. Monitoring known procedure- and contrast-related risks (e.g., post-lumbar puncture headache, nausea, dizziness) as well as any unexpected adverse events over the study and follow-up period provides the critical foundation for ethical justification and regulatory decision-making and is a prerequisite for future feasibility and efficacy-driven studies.
Time frame: 12-week study period.
Participant-level MRI detection status (yes/no) of contrast in the cerebral SAS
Technical feasibility is assessed by determining whether IT administered GBCA can be visually detected in the cerebral SAS at 24 hours under exploratory Phase 1 conditions. As this is a pilot safety study with limited prior human data, feasibility is not used as a stopping criterion. Instead, MRI visibility of contrast will inform adaptive dose escalation. If no or insufficient contrast enhancement is observed in 3 to 5 participants at the initial dose level (0.25 ml), the dose may be escalated to 0.5 ml to improve detectability. This predefined adaptation is intended to support appropriate dose selection for subsequent studies while maintaining the focus on safety.
Time frame: 24 hours
Plan to share: Yes — All IPD that results in publication
Supporting information: Clinical study report
Time frame: 6 months after publication
Access criteria: IPD will be shared under tech transfer agreements.
Start is estimated for Nov 2026; primary completion for Mar 2028, 15 months later.
Start moved 34 times since we started tracking on Sep 25, 2026: Sep 2026 → Nov 2026, last on Nov 13, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Nov 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
National Institute of Neurological Disorders and Stroke (NINDS) →