Idiopathic Intracranial Hypertension (IIH)
Conditions
Keywords
Intracranial hypertension, papillary edema, stenting, transverse sinus vein, chronic headache, tinnitus
Brief summary
This study is aimed at patients suffering from recently discovered intracranial hypertension, caracterized by visual loss, chronic headache and/or tinnitus. The goal is to evaluate if stenting of a specific vein in the brain could decrease the hypertension and improve associated symptoms. Patients will be randomly assigned in either best medical care group (recommended medication associated with weight loss) or interventional group (best medical car + stenting of the specific vein) and will undergo specific follow-up visits after 1, 3 and 12 months.
Detailed description
The DIVE-IIN-EARLY trial is a multicenter randomized controlled trial designed to evaluate whether transverse venous sinus stenting is more effective than best medical therapy alone as first-line treatment for patients with idiopathic intracranial hypertension (IIH). The study targets patients with a new diagnosis of IIH with bilateral transverse sinus stenosis or unilateral stenosis of the dominant transverse sinus with a hypoplastic contralateral sinus. Idiopathic intracranial hypertension is, in most cases, associated with narrowing of the transverse sinus vein, which may be the cause of increased intracranial blood pressure, resulting in the accumulation and increase in intracranial fluid pressure. This increased pressure is thought to be responsible for papilledema, chronic headaches, and tinnitus, among other symptoms. Restoring a normal luminal diameter of the transverse sinus using a stent could therefore allow for the rapid restoration of normal intracranial pressures and an improvement in various symptoms. Stent implantation in the transverse sinus is now part of standard care, but no large-scale clinical trial has formally established the superiority of the technique compared to the standard of care (drug therapy combined with weight gain). This study aims to provide evidence on the potential benefits of transverse venous sinus stenting as a treatment option for patients with idiopathic intracranial hypertension, which could significantly change the current management approach to this disease. Usual medication for this condition is acetazolamide, but it's efficacy as well as it's tolerance is mostly poor. By proposing stenting in the early phase of the disease, one could avoid long term symptoms such as loss of vision and chronic headache.
Interventions
Acetazolamide will be introduced at the time of papilledema discovery. Weight loss will be recommended.
DEVICEIntervention (stenting)
Transverse venous sinus will be stented by neuro-radiological intervention
Sponsors
Ministère de la Santé
University Hospital, Montpellier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject is ≥ 18 years old at inclusion. 2. Subject with definite new diagnosis (˂ 3 months) of IIH satisfying the modified Dandy criteria (A to E) 3. Subject with intracranial TVS stenosis on dominant transverse sinus and hypoplastic contralateral one (or bilateral TVS stenosis) diagnosed on MRI 4. Normal MRI findings excepted intracranial TVS stenosis or IIH related abnormalities 5. Subject with ophthalmologic IIH symptoms and signs (RNFL ≥ 130 µm, Frisen score ≥ 2, and absence of differential diagnostic) 6. Subject without macular ganglion cells atrophy seen on OCT 7. Patient having received information about data collection and having signed and dated an Informed Consent Form 8. Subjects must be able to attend all scheduled visits and to comply with all trial procedures 9. Subjects must be covered by public health insurance
Exclusion criteria
1. Subject previously treated with acetazolamide for IIH 2. Known contrast product, Nickel, titanium allergy 3. Exposure to an oral drug, substance, or disorder that has been associated with elevation of intracranial pressure within 2 months of diagnosis (lithium, vitamin A, tetracycline and related compounds) 4. History of intracranial venous thrombosis or intracranial neoplasia 5. Fulminant decrease of visual acuity due to the IIH defined as a visual loss (of the most seriously impaired eye) of at least 3/10 (from corrected vision) within 4 weeks, in absence of any other ophthalmologic pathology and Mean Deficit of visual field superior to -10 dB 6. Macular ganglion cells atrophy seen on OCT 7. Optic nerve atrophy 8. Amblyopia 9. Refractive error greater ±8 sphere or more than ±3 in cylinder in either eye if there are abnormalities in funduscopy (optic disc tilt, staphyloma), previous glaucoma, other disorders causing visual loss 10. Pregnancy: if a woman is of childbearing potential a urine or serum beta HCG test is positive 11. Patient with a severe or fatal comorbidity that will likely prevent improvement or follow-up or that will render the procedure unlikely to benefit the patient. 12. Evidence of intracranial hemorrhage (subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), etc.) 13. Life expectancy under 6 months 14. Chronic IIH 15. Patients with renal failure (creatinine \> 1.5 mg/dl and/or creatinine clearance \< 60 mL/min, except if patient is already on hemodialysis) 16. History of previously implanted intra-cranial sinus stent 17. Previous gastric bypass surgery 18. Contra-indication to general anesthesia 19. Contra-indication to aspirin, clopidogrel or other P2Y12 anti-aggregant 20. History of chronic obstructive pulmonary disease or other severe respiratory disease 21. History of deep vein thrombosis or pulmonary embolism 22. History of atrial fibrillation or other risks of stroke 23. Cerebral vascular lesions (arteriovenous malformation, arteriovenous fistula, aneurysms, significant stenosis of extra- or intra-cranial vessels other than the targeted venous sinus stenosis, intracranial artery dissection, etc.). 24. Anatomical anomaly of the venous sinus which would prevent safe catheterization and stenting 25. Subject who are in a dependency or employment with the sponsor or the investigator 26. Participation in another clinical trial or administration of an unapproved drug within the last 4 weeks before the screening date 27. Subject protected according to the French Public Health Code (e.g. patients under law protection, prisoners, pregnant, parturient or lactating women, and patients under guardianship/curatorship)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of patients with resolved papilledema and normalization of intra-cranial pressure | 3 months | Rate of patients with resolved papilledema (defined as Frisén scale grade 0-1 on OCT, without ganglion cells damage, and RNFL ˂ 130 µm) and normalization of intra-cranial pressure (defined as ≤ 25 cm H20 or 18 mmHg measured on lumbar puncture) at 3 months. Papilledema will be studied in the most affected eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monthly headache days | 3 and 12 months | Change in monthly headache days (within the last month) reported on patients' dairy |
| THI score | 3 and 12 months | Change in THI (Tinnitus Handicap Inventory) score |
| Visual field | 3 and 12 months | Change in decibel of Mean Deficit visual field assessed on automated perimetry in both eyes with Humphrey Field Analyzer SITA Standard 24-2 test pattern. Each participant will have at least 2 initial visual field examinations conducted at least 30 minutes apart. The 2 Perimetric Mean Deviation (PMD) measurements will be averaged. |
| Visual acuity | 3 and 12 months | Change of visual acuity score evaluated on ETDRS (far vision) at 4 meters and reproducible lighting, and Parinaud scale (near vision) using the best optical correction |
| HIT-6 grading scale score | 3 and 12 months | Change in mean HIT-6 grading scale score (patient's questionnaire containing 6 questions to evaluate the severity of headache) |
| Patient's autonomy | 3 and 12 months | Change in quality of life assessed on EQ5D questionnaire |
| Patient's cognition | 12 months | Change in Montreal Cognitive Assessment (MoCA) |
| Cognition | 12 months | Change in Trail Making Test (TMT) A and B |
| Papilledema | 3 and 12 months | Change of papilledema assessed on Frisen score and RNFL on OCT |
Countries
France
Contacts
Primary ContactAnne DUCROS, MD, PhD
Backup ContactFédérico CAGNAZZO, MD, PhD
Outcome results
None listed