Idiopathic Intracranial HypertensionLYMPHIMAGIIHNCT05762367
MR Lymphatic Imaging in Idiopathic Intracranial Hypertention
A study testing 3T MRI with Gadobutrol injection in people with Idiopathic Intracranial Hypertension, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial summary
In the brain and its borders, blood vessels coexist with lymphatic vessels exclusively in the dura mater, the outermost layer of meninges. Dural lymphatics are present in various vertebrate species, including humans, and a cluster of experimental studies in the mouse strongly suggest their relevance in the… Read more about this study
- Who is it for?
- Ages 20 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Idiopathic Intracranial Hypertension
- What is being tested?
- 3T MRI with Gadobutrol injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- 10 Mar 2023to 11 May 2025
- Phase
- Interventional
- 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 20 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- For all participants:
- Age > 18 years and ≤ 40 years female gender Absence of previous neurosurgical or endovascular neurological history Participant able to express her consent Medical insurance
- For participants with IIH No required criterion of severity or evolution of IIH Definite diagnosis of IIH according to Dandy's modified criteria. All of the following criteria must be met and verified by medical reports or certificates from a neurologist, especially the value of the CSF opening pressure measured during the lumbar puncture must be clearly noted on the reports
- History of papilledema
- Normal neurological examination, except for paralysis of the VIth cranial nerve
- Neuroimaging: normal cerebral parenchyma without hydrocephalus, intracranial expansive process, or structural anomaly, and absence of meningeal contrast enhancement in MRI without and with contrast product. A venous angio-MRI is necessary in atypical patients; if MRI is unavailable or contraindicated, a brain scan without and with contrast product can be done in combination with a venous angioscan with contrast injection
Show all 9Show fewer
- Normal CSF composition
- High CSF opening pressure (≥ 25 cm of water) obtained from a lumbar puncture performed in lateral decubitus
- For healthy volunteers No previous history of neurological or neurosurgical disorder
Who cannot join
- For all participants Pregnant or breastfeeding woman Contraindication to cerebral MRI: metallic implant, pacemaker, artificial heart valve, cerebral vascular malformation, aneurysm clips, metallic fragments, artificial implants, peripheral or neural pacemaker, insulin pump, intravenous catheter, epilepsy , metallic contraceptive device, claustrophobia, refusal to be informed in case of abnormal MRI (with a significant medical abnormality) Hypersensitivity to the active substance of the contrast agent or to any of the excipients (Sodium calcobutrol, Trometamol, 1N hydrochloric acid (pH adjustment), Water for injections) lumbar puncture in the month preceding the brain MRI Neurological tumoral, degenerative, vascular, inflammatory or progressive pathology Renal or hepatic impairment MRI with gadolinium injection performed in the 7 days preceding the inclusion visit Person subject to a measure of legal protection (safeguard of justice, curatorship, guardianship), deprived of liberty by judicial or administrative decision
- For participants with IIH Participants with a probable but not definite diagnosis of IIH according to the Dandy modified criteria
- For healthy volunteers Chronic headaches (>15 days per month) Uncorrected and/or unlabeled visual symptoms (visual blurriness, diplopia, visual eclipses, papilledema, optic atrophy)
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Neuroradiologie, Groupe Hospitalier Pitié Salpêtrière, Paris, France
Paris, Île-de-France Region, 75000
About this study
Official title: MR Lymphatic Imaging in Idiopathic Intracranial Hypertension
In the brain and its borders, blood vessels coexist with lymphatic vessels exclusively in the dura mater, the outermost layer of meninges. Dural lymphatics are present in various vertebrate species, including humans, and a cluster of experimental studies in the mouse strongly suggest their relevance in the pathophysiology of chronic and acute neurological disorders in humans. Demonstrating this assumption is however still at stake and the lymphatic regulatory mechanisms involved remain poorly characterized.
Our main objective is to assess dural lymphatics contribution to the pathophysiology of a rare neurological disorder: idiopathic intracranial hypertension (IIH). In IIH patients, intracranial hypertension causes severe headache and visual loss and is associated with a stenosis of dural sinuses and abnormal retention of fluids in the central nervous system. Angioplasty treatment by stent placement into venous sinuses is frequently followed by recurrent stenosis suggesting that, in addition to the blood vessels, the duro-lymphatic environment contributes to disease progression.
Read more
Several studies have found hot spots of lymphatic uptake at confluence points between cerebral veins and dural sinuses. Based on this premise, the investigators predict a causal link between lymphatic and venous behavior around dural sinuses and the remodeling of dural lymphatics in neurovascular conditions such as IIH.
Our approach will combine radiological observations from human patients with experimental analyses in mouse models.
The investigators have recently developed a technique of high resolution vessel wall imaging to explore and compare the lymphatic networks between individuals. This advanced MR-imaging technique has been validated through a translational study comparing the lymphatic networks in mice and humans (Jacob et al. 2022, JExpMed). Using this tool, the investigators aim to monitor dural lymphatic and sinus wall abnormalities in patients with IIH. In this view, cohorts of IIH patients and controls without neurological disorders (n = 20/cohort) will be scanned by MRI to perform high resolution vessel wall imaging of the dural lymphatics, sinus and cerebral veins.
Read the detailed description
Fluid retention in idiopathic intracranial hypertension (IIH) (Lenck, Neurology 2018) preferentially occur at the "hot spots" of the dural lymphatic system described in mice (Ahn, Nature 2019; Ma, Nat Commun 2017; Louveau, Nat Neurosci. 2018). While the pathophysiological mechanisms of IIH are still unknown, dural venous stenoses are constant and endovascular treatment by stenting allow to decrease the intracranial pressure in most cases, suggesting a crucial role of these stenoses in the pathological process of IIH. However, the cause of dural venous sinsu stenoses are still unknown. IIH corresponds to a paradigmatic model of neurological disorder associating vascular and fluid dysfunction, since raised intracranial pressure and stenosis of the dural venous sinuses are in constant association. Dural venous stenoses are located at the transverse sinus-sigmoid sinus junction, a lymphatic reuptake point or 'hot spot', in mice. The pathological process leading to the progressive obstruction of the vein seems to directly affect the wall of the dural sinus and only secondarily its lumen (Lenck, Neurology 2018; Lenck, AJNR 2021; Lenck, Neurosurgery 2017; Kedra, JNNP 2021). Impaired lymphatic reuptake could also contribute to this pathology as suggested by the accumulation of fluid at the level of the cribriform plate, or at the Meckel's cave. Thus, the association between cerebral venous outflow obstruction and CSF accumulation in the dura mater at the hotspots of the lymphatic system suggests impaired dural lymphatic system and veno-lymphatic relationships in IIH.
Since 2017, and the first demonstration by MRI of the dural lymphatics in humans by Absinta (Absinta, Elife. 2017), VWI (Vessel Wall Imaging) techniques have been significantly improved in terms of resolution allowing an analysis of the cerebral vessel wall (Xie et al. Magn Reson Med. 2016). These techniques were mainly developed in the context of arterial wall abnormalities but have never been applied to the study of the dural venous wall and its lymphatics. The 3D T1 SPACE (variable flip angle turbo spin echo) - DANTE (delay alternating with nutation for tailored excitation) sequence has been recently developed and allows to improve the suppression of the intravascular signal and consequently to improve the resolution of the vessel wall imaging (Xie et al. Magn Reson Med. 2016). In collaboration with Siemens, our team has further developed and improved this advanced VWI technique and performed a translational comparative study comparing the dural lymphatic network between humans and mice to validate its preliminary results (Jacob, J. Exp. Med 2022). This study allowed to characterize the entire dural lymphatic network with high resolution and in three dimensions, as well as its connections with the cervical lymph nodes in humans. Furthermore, the investigators firstly demonstrated the presence of a ventral lymphatic network around the cavernous sinus. Our results seem superior to previous radiological protocols for qualitative and large field analysis of the parasinus and its lymphatics. Image processing by dedicated segmentation software (3D-Slicer) allows a three-dimensional reconstruction of the veno-lymphatic network in humans but also its quantitative analysis. This represents a major scientific breakthrough allowing objective comparisons of these networks between pathologies.
IIH is a still mysterious and poorly known entity at the frontiers of neurology, neurosurgery and ophthalmology. It affects young women of childbearing age and can lead to a major deterioration in the quality of life through headaches, visual impairment or even the blindness that it can cause. All available treatments (Acetazolamide, CSF diversion, venous stent) are active on the symptoms of the disease but do not target its cause. Their effectiveness is limited, they are invasive and associated with significant risks and adverse effects. More effective and less invasive therapies, directly targeting the biological cause of IIH, therefore represent a major medical challenge.
However, a prerequisite before considering such approach is to understand the pathophysiological bases underlying IIH. Our project combines innovative experimental approaches in surgery and imaging on murine models with the previously described development of lymphatic imaging in humans in patients with IIH and controls. The ultimate goal of our research is to open therapeutic avenues with realistic potential to improve the prognosis of patients with IIH.
In this study the investigators will enroll 20 female patients with IIH and 20 female healthy volunteers between 20 and 40 years old.
Our primary objective is to compare the anatomy of the dural lymphatic network in patients with IIH compared to healthy subjects.
Our secondary objectives are:
- Characterization in high resolution VWI imaging of dural venous sinus stenoses in IIH
- Morphometric study of the cervical lymphatic network in patients with IIH compared to healthy subjects.
- Comparison of the volume of the different compartments of the skull between patients with IIH and healthy volunteers (cerebral volume, intraventricular CSF volume (lateral ventricles), intradural venous volume)
- Conditions
- Idiopathic Intracranial Hypertension
- Being tested
- 3T MRI with Gadobutrol injection
- Keywords
- Dural venous stenoses, MRI, Vessel Wall Imaging, Headache, Papilledema
- Medical subject headings
- Pseudotumor Cerebri, Headache, Papilledema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3T MRI with Gadobutrol injectionDiagnostic test
MRI will be performed in all participants before and after Gadobutrol injection
| Study group | Role | What they receive |
|---|---|---|
| Patients with IIH | Experimental | Female patients with IIH between 20 and 40 years old Receives: Diagnostic Test: 3T MRI with Gadobutrol injection |
| Healthy volunteers | Active comparator | Female healthy volunteers between 20 and 40 years old Receives: Diagnostic Test: 3T MRI with Gadobutrol injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morphometric study of the dural lymphatic network in patients with IIH vs controls
Measurement of the dural lymphatic network volume (mm3) in patients with IIH vs controls
Measured: Immediate
Secondary outcomes (3)
Characterization of lateral sinus stenoses using high resolution vessel wall imaging in patients with IIH
Measurement of the volume of the dural lymphatic vessels at the transverse-sigmoid junction in patients with IIH vs control Measurement of the thickness of the parasinus at the transverse-sigmoid junction in patients with IIH vs control Measurement of the stenosis (ratio intraluminal diameter at the level of the stenosis and intraluminal diameter of the transverse sinus upstream) in patients with IIH Presence of intraluminal granulation in patients with IIH vs control Qualitative analysis of dural venous stenoses in patients with IIH
Measured: Immediate
Morphometric study of the cervical lymphatic network in patients with IIH vs controls
Comparison of the volume of the cervical lymph nodes in patients with IIH vs controls
Measured: Immediate
Comparison of the volumes of the different compartments of the skull in patients with IIH vs controls
Brain volume in patients with IIH vs controls Intraventricular CSF volume of the lateral ventricles in patients with IIH vs controls Intradural venous volume in patients with IIH vs controls
Measured: Immediate
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2023
- Study start10 Mar 2023
- Primary completion11 Apr 2025
- Study completion11 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Intracranial HypertensionStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 20 patients with IIH and 20 volunteers paired on age (20-40 yo) and gender will be prospectively enrolled in the study
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05762367
- Sponsor's protocol ID
- C22-13
- Other IDs
- 2022-A01422-41
- Acronym
- LYMPHIMAGIIH
- Status last verified
- Jan 2025
- First submitted
- 28 Feb 2023
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ahn JH, Cho H, Kim JH, Kim SH, Ham JS, Park I, Suh SH, Hong SP, Song JH, Hong YK, Jeong Y, Park SH, Koh GY. Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nature. 2019 Aug;572(7767):62-66. doi: 10.1038/s41586-019-1419-5. Epub 2019 Jul 24.
PubMed 31341278Lenck S, Radovanovic I, Nicholson P, Hodaie M, Krings T, Mendes-Pereira V. Idiopathic intracranial hypertension: The veno glymphatic connections. Neurology. 2018 Sep 11;91(11):515-522. doi: 10.1212/WNL.0000000000006166.
PubMed 30201744Ma Q, Ineichen BV, Detmar M, Proulx ST. Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice. Nat Commun. 2017 Nov 10;8(1):1434. doi: 10.1038/s41467-017-01484-6.
PubMed 29127332Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018 Oct;21(10):1380-1391. doi: 10.1038/s41593-018-0227-9. Epub 2018 Sep 17.
PubMed 30224810Lenck S, Nicholson P. Cerebral Venous Wall Diseases: The Other Side of the Picture. AJNR Am J Neuroradiol. 2021 Jan;42(2):297-298. doi: 10.3174/ajnr.A6914. Epub 2021 Jan 7. No abstract available.
PubMed 33414232Lenck S, Vallee F, Labeyrie MA, Touitou V, Saint-Maurice JP, Guillonnet A, Tantot A, Crassard I, Bernat AL, Houdart E. Stenting of the Lateral Sinus in Idiopathic Intracranial Hypertension According to the Type of Stenosis. Neurosurgery. 2017 Mar 1;80(3):393-400. doi: 10.1227/NEU.0000000000001261.
PubMed 27218234Kedra A, Lahlouh M, Shotar E, Chenoune Y, Boistard L, Boussac A, Shor N, Savatovsky J, Hage R, Touitou V, Nicholson P, Clarencon F, Piotin M, Blanc R, Lenck S. Global collapse of the dural sinuses after venous stenting in idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry. 2021 Dec;92(12):1363-1364. doi: 10.1136/jnnp-2020-325717. Epub 2021 Jun 24. No abstract available.
PubMed 34168084Absinta M, Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, Louveau A, Zaghloul KA, Pittaluga S, Kipnis J, Reich DS. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017 Oct 3;6:e29738. doi: 10.7554/eLife.29738.
PubMed 28971799Xie Y, Yang Q, Xie G, Pang J, Fan Z, Li D. Improved black-blood imaging using DANTE-SPACE for simultaneous carotid and intracranial vessel wall evaluation. Magn Reson Med. 2016 Jun;75(6):2286-94. doi: 10.1002/mrm.25785. Epub 2015 Jul 8.
PubMed 26152900Jacob L, de Brito Neto J, Lenck S, Corcy C, Benbelkacem F, Geraldo LH, Xu Y, Thomas JM, El Kamouh MR, Spajer M, Potier MC, Haik S, Kalamarides M, Stankoff B, Lehericy S, Eichmann A, Thomas JL. Conserved meningeal lymphatic drainage circuits in mice and humans. J Exp Med. 2022 Aug 1;219(8):e20220035. doi: 10.1084/jem.20220035. Epub 2022 Jul 1.
PubMed 35776089El Kamouh MR, Spajer M, Singhabahu R, Joly Marolany AL, Sailor KA, Mouton L, Doukhi D, Koundal S, Metcalfe T, Langui D, Grine A, Boye K, Saceanu Leser F, Ninnemann J, Gottschalk J, Sadeghi C, Xu H, Boisserand LSB, Akbar D, Van Wassenhove J, Ruze A, Nasri A, Bourrienne MC, Buscher E, Hong YK, Mazighi M, Lledo PM, Benveniste H, Santin M, Eichmann A, Lehericy S, Thomas JL, Lenck S. Cerebral venous blood flow regulates intracerebral pressure and brain clearance via meningeal lymphatic vessels. Nat Neurosci. 2026 Sep;29(9):2190-2203. doi: 10.1038/s41593-026-02358-1. Epub 2026 Jul 22.
PubMed 42487032
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MR Lymphatic Imaging in Idiopathic Intracranial Hypertension
- ClinicalTrials.gov ID
- NCT05762367
- Acronym / sponsor ID
- LYMPHIMAGIIH / C22-13
- Conditions
- Idiopathic Intracranial Hypertension
- Keywords
- Dural venous stenoses, MRI, Vessel Wall Imaging, Headache, Papilledema
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- 10 Mar 2023 (actual)
- Primary completion
- 11 Apr 2025 (actual)
- Study completion
- 11 May 2025 (actual)
- First posted
- 9 Mar 2023 (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.
In the brain and its borders, blood vessels coexist with lymphatic vessels exclusively in the dura mater, the outermost layer of meninges. Dural lymphatics are present in various vertebrate species, including humans, and a cluster of experimental studies in the mouse strongly suggest their relevance in the pathophysiology of chronic and acute neurological disorders in humans. Demonstrating this assumption is however still at stake and the lymphatic regulatory mechanisms involved remain poorly characterized.
Our main objective is to assess dural lymphatics contribution to the pathophysiology of a rare neurological disorder: idiopathic intracranial hypertension (IIH). In IIH patients, intracranial hypertension causes severe headache and visual loss and is associated with a stenosis of dural sinuses and abnormal retention of fluids in the central nervous system. Angioplasty treatment by stent placement into venous sinuses is frequently followed by recurrent stenosis suggesting that, in addition to the blood vessels, the duro-lymphatic environment contributes to disease progression.
Several studies have found hot spots of lymphatic uptake at confluence points between cerebral veins and dural sinuses. Based on this premise, the investigators predict a causal link between lymphatic and venous behavior around dural sinuses and the remodeling of dural lymphatics in neurovascular conditions such as IIH.
Our approach will combine radiological observations from human patients with experimental analyses in mouse models.
The investigators have recently developed a technique of high resolution vessel wall imaging to explore and compare the lymphatic networks between individuals. This advanced MR-imaging technique has been validated through a translational study comparing the lymphatic networks in mice and humans (Jacob et al. 2022, JExpMed). Using this tool, the investigators aim to monitor dural lymphatic and sinus wall abnormalities in patients with IIH. In this view, cohorts of IIH patients and controls without neurological disorders (n = 20/cohort) will be scanned by MRI to perform high resolution vessel wall imaging of the dural lymphatics, sinus and cerebral veins.
Detailed description
Fluid retention in idiopathic intracranial hypertension (IIH) (Lenck, Neurology 2018) preferentially occur at the "hot spots" of the dural lymphatic system described in mice (Ahn, Nature 2019; Ma, Nat Commun 2017; Louveau, Nat Neurosci. 2018). While the pathophysiological mechanisms of IIH are still unknown, dural venous stenoses are constant and endovascular treatment by stenting allow to decrease the intracranial pressure in most cases, suggesting a crucial role of these stenoses in the pathological process of IIH. However, the cause of dural venous sinsu stenoses are still unknown. IIH corresponds to a paradigmatic model of neurological disorder associating vascular and fluid dysfunction, since raised intracranial pressure and stenosis of the dural venous sinuses are in constant association. Dural venous stenoses are located at the transverse sinus-sigmoid sinus junction, a lymphatic reuptake point or 'hot spot', in mice. The pathological process leading to the progressive obstruction of the vein seems to directly affect the wall of the dural sinus and only secondarily its lumen (Lenck, Neurology 2018; Lenck, AJNR 2021; Lenck, Neurosurgery 2017; Kedra, JNNP 2021). Impaired lymphatic reuptake could also contribute to this pathology as suggested by the accumulation of fluid at the level of the cribriform plate, or at the Meckel's cave. Thus, the association between cerebral venous outflow obstruction and CSF accumulation in the dura mater at the hotspots of the lymphatic system suggests impaired dural lymphatic system and veno-lymphatic relationships in IIH.
Since 2017, and the first demonstration by MRI of the dural lymphatics in humans by Absinta (Absinta, Elife. 2017), VWI (Vessel Wall Imaging) techniques have been significantly improved in terms of resolution allowing an analysis of the cerebral vessel wall (Xie et al. Magn Reson Med. 2016). These techniques were mainly developed in the context of arterial wall abnormalities but have never been applied to the study of the dural venous wall and its lymphatics. The 3D T1 SPACE (variable flip angle turbo spin echo) - DANTE (delay alternating with nutation for tailored excitation) sequence has been recently developed and allows to improve the suppression of the intravascular signal and consequently to improve the resolution of the vessel wall imaging (Xie et al. Magn Reson Med. 2016). In collaboration with Siemens, our team has further developed and improved this advanced VWI technique and performed a translational comparative study comparing the dural lymphatic network between humans and mice to validate its preliminary results (Jacob, J. Exp. Med 2022). This study allowed to characterize the entire dural lymphatic network with high resolution and in three dimensions, as well as its connections with the cervical lymph nodes in humans. Furthermore, the investigators firstly demonstrated the presence of a ventral lymphatic network around the cavernous sinus. Our results seem superior to previous radiological protocols for qualitative and large field analysis of the parasinus and its lymphatics. Image processing by dedicated segmentation software (3D-Slicer) allows a three-dimensional reconstruction of the veno-lymphatic network in humans but also its quantitative analysis. This represents a major scientific breakthrough allowing objective comparisons of these networks between pathologies.
IIH is a still mysterious and poorly known entity at the frontiers of neurology, neurosurgery and ophthalmology. It affects young women of childbearing age and can lead to a major deterioration in the quality of life through headaches, visual impairment or even the blindness that it can cause. All available treatments (Acetazolamide, CSF diversion, venous stent) are active on the symptoms of the disease but do not target its cause. Their effectiveness is limited, they are invasive and associated with significant risks and adverse effects. More effective and less invasive therapies, directly targeting the biological cause of IIH, therefore represent a major medical challenge.
However, a prerequisite before considering such approach is to understand the pathophysiological bases underlying IIH. Our project combines innovative experimental approaches in surgery and imaging on murine models with the previously described development of lymphatic imaging in humans in patients with IIH and controls. The ultimate goal of our research is to open therapeutic avenues with realistic potential to improve the prognosis of patients with IIH.
In this study the investigators will enroll 20 female patients with IIH and 20 female healthy volunteers between 20 and 40 years old.
Our primary objective is to compare the anatomy of the dural lymphatic network in patients with IIH compared to healthy subjects.
Our secondary objectives are:
- Characterization in high resolution VWI imaging of dural venous sinus stenoses in IIH
- Morphometric study of the cervical lymphatic network in patients with IIH compared to healthy subjects.
- Comparison of the volume of the different compartments of the skull between patients with IIH and healthy volunteers (cerebral volume, intraventricular CSF volume (lateral ventricles), intradural venous volume)
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 20 patients with IIH and 20 volunteers paired on age (20-40 yo) and gender will be prospectively enrolled in the study
| Arm | Type | Receives |
|---|---|---|
| Patients with IIH | Experimental | Diagnostic Test: 3T MRI with Gadobutrol injectionFemale patients with IIH between 20 and 40 years old |
| Healthy volunteers | Active comparator | Diagnostic Test: 3T MRI with Gadobutrol injectionFemale healthy volunteers between 20 and 40 years old |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- For all participants:
- Age > 18 years and ≤ 40 years female gender Absence of previous neurosurgical or endovascular neurological history Participant able to express her consent Medical insurance
- For participants with IIH No required criterion of severity or evolution of IIH Definite diagnosis of IIH according to Dandy's modified criteria. All of the following criteria must be met and verified by medical reports or certificates from a neurologist, especially the value of the CSF opening pressure measured during the lumbar puncture must be clearly noted on the reports
- For healthy volunteers No previous history of neurological or neurosurgical disorder
Key exclusion criteria (3 listed)
- For all participants Pregnant or breastfeeding woman Contraindication to cerebral MRI: metallic implant, pacemaker, artificial heart valve, cerebral vascular malformation, aneurysm clips, metallic fragments, artificial implants, peripheral or neural pacemaker, insulin pump, intravenous catheter, epilepsy , metallic contraceptive device, claustrophobia, refusal to be informed in case of abnormal MRI (with a significant medical abnormality) Hypersensitivity to the active substance of the contrast agent or to any of the excipients (Sodium calcobutrol, Trometamol, 1N hydrochloric acid (pH adjustment), Water for injections) lumbar puncture in the month preceding the brain MRI Neurological tumoral, degenerative, vascular, inflammatory or progressive pathology Renal or hepatic impairment MRI with gadolinium injection performed in the 7 days preceding the inclusion visit Person subject to a measure of legal protection (safeguard of justice, curatorship, guardianship), deprived of liberty by judicial or administrative decision
- For participants with IIH Participants with a probable but not definite diagnosis of IIH according to the Dandy modified criteria
- For healthy volunteers Chronic headaches (>15 days per month) Uncorrected and/or unlabeled visual symptoms (visual blurriness, diplopia, visual eclipses, papilledema, optic atrophy)
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 |
|---|---|---|
| 3T MRI with Gadobutrol injectionMRI will be performed in all participants before and after Gadobutrol injection | Diagnostic test | Healthy volunteers, Patients with IIH |
Primary outcome
Morphometric study of the dural lymphatic network in patients with IIH vs controls
Time frame: Immediate
Measurement of the dural lymphatic network volume (mm3) in patients with IIH vs controls
3 secondary outcomes
Characterization of lateral sinus stenoses using high resolution vessel wall imaging in patients with IIH
Time frame: Immediate
Morphometric study of the cervical lymphatic network in patients with IIH vs controls
Time frame: Immediate
Comparison of the volumes of the different compartments of the skull in patients with IIH vs controls
Time frame: Immediate
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 8 Oct 2026.
- Background: PubMed 31341278Ahn JH, Cho H, Kim JH, Kim SH, Ham JS, Park I, Suh SH, Hong SP, Song JH, Hong YK, Jeong Y, Park SH, Koh GY. Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nature. 2019 Aug;572(7767):62-66. doi: 10.1038/s41586-019-1419-5. Epub 2019 Jul 24.
- Background: PubMed 30201744Lenck S, Radovanovic I, Nicholson P, Hodaie M, Krings T, Mendes-Pereira V. Idiopathic intracranial hypertension: The veno glymphatic connections. Neurology. 2018 Sep 11;91(11):515-522. doi: 10.1212/WNL.0000000000006166.
- Background: PubMed 29127332Ma Q, Ineichen BV, Detmar M, Proulx ST. Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice. Nat Commun. 2017 Nov 10;8(1):1434. doi: 10.1038/s41467-017-01484-6.
- Background: PubMed 30224810Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018 Oct;21(10):1380-1391. doi: 10.1038/s41593-018-0227-9. Epub 2018 Sep 17.
- Background: PubMed 33414232Lenck S, Nicholson P. Cerebral Venous Wall Diseases: The Other Side of the Picture. AJNR Am J Neuroradiol. 2021 Jan;42(2):297-298. doi: 10.3174/ajnr.A6914. Epub 2021 Jan 7. No abstract available.
- Background: PubMed 27218234Lenck S, Vallee F, Labeyrie MA, Touitou V, Saint-Maurice JP, Guillonnet A, Tantot A, Crassard I, Bernat AL, Houdart E. Stenting of the Lateral Sinus in Idiopathic Intracranial Hypertension According to the Type of Stenosis. Neurosurgery. 2017 Mar 1;80(3):393-400. doi: 10.1227/NEU.0000000000001261.
- Background: PubMed 34168084Kedra A, Lahlouh M, Shotar E, Chenoune Y, Boistard L, Boussac A, Shor N, Savatovsky J, Hage R, Touitou V, Nicholson P, Clarencon F, Piotin M, Blanc R, Lenck S. Global collapse of the dural sinuses after venous stenting in idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry. 2021 Dec;92(12):1363-1364. doi: 10.1136/jnnp-2020-325717. Epub 2021 Jun 24. No abstract available.
- Background: PubMed 28971799Absinta M, Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, Louveau A, Zaghloul KA, Pittaluga S, Kipnis J, Reich DS. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017 Oct 3;6:e29738. doi: 10.7554/eLife.29738.
- Background: PubMed 26152900Xie Y, Yang Q, Xie G, Pang J, Fan Z, Li D. Improved black-blood imaging using DANTE-SPACE for simultaneous carotid and intracranial vessel wall evaluation. Magn Reson Med. 2016 Jun;75(6):2286-94. doi: 10.1002/mrm.25785. Epub 2015 Jul 8.
- Background: PubMed 35776089Jacob L, de Brito Neto J, Lenck S, Corcy C, Benbelkacem F, Geraldo LH, Xu Y, Thomas JM, El Kamouh MR, Spajer M, Potier MC, Haik S, Kalamarides M, Stankoff B, Lehericy S, Eichmann A, Thomas JL. Conserved meningeal lymphatic drainage circuits in mice and humans. J Exp Med. 2022 Aug 1;219(8):e20220035. doi: 10.1084/jem.20220035. Epub 2022 Jul 1.
- Results publication: PubMed 42487032El Kamouh MR, Spajer M, Singhabahu R, Joly Marolany AL, Sailor KA, Mouton L, Doukhi D, Koundal S, Metcalfe T, Langui D, Grine A, Boye K, Saceanu Leser F, Ninnemann J, Gottschalk J, Sadeghi C, Xu H, Boisserand LSB, Akbar D, Van Wassenhove J, Ruze A, Nasri A, Bourrienne MC, Buscher E, Hong YK, Mazighi M, Lledo PM, Benveniste H, Santin M, Eichmann A, Lehericy S, Thomas JL, Lenck S. Cerebral venous blood flow regulates intracerebral pressure and brain clearance via meningeal lymphatic vessels. Nat Neurosci. 2026 Sep;29(9):2190-2203. doi: 10.1038/s41593-026-02358-1. Epub 2026 Jul 22.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 3T MRI with Gadobutrol injection in people with Idiopathic Intracranial Hypertension, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
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 9 inclusion and 3 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 8 Oct 2026. 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 France. 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?
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?
Morphometric study of the dural lymphatic network in patients with IIH vs controls (time frame: Immediate). 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 NCT05762367, which also lists 11 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 8 Oct 2026.