Biomarkers in the Etiology of Idiopathic Intracranial Hypertension

NCT06059703 | Recruiting

• 1 other identifier: RECHMPL22_0565
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Idiopathic intracranial hypertension (IIH) is a condition characterized by an increase in intracranial pressure (ICP), papilledema with a risk of permanent visual loss, and severe headaches that profoundly affect quality of life. To date the exact pathophysiology of IIH remains unknown. IIH is considered a complex neurometabolic and neuroendocrine disorder, favored by female gender, and obesity. In the majority of patients (80% of the cases) IIH is associated with obstruction of cerebral venous drainage with stenosis of the transverse sinus. This stenosis may be the main underlying cause in the so-called "venogenic" form of IIH. Equally, in the absence of a stenosis, obstruction may occur when otherwise normal venous sinuses are compressed by the increased ICP, the so-called "non-venogenic" form of IIH. An innovative treatment of IIH with associated venous stenosis includes stenting of the transverse sinus stenosis. This strategy may allow resolution of papilledema and ICP reduction rates up to 80%. Although the pathogenesis of IIH is still poorly understood, inflammatory mechanisms, autoimmune reactions, and hormonal abnormalities of notably androgens, have been proposed to contribute to its pathophysiology. The function of the blood-brain barrier (BBB) has been studied by determining the prevalence of extravasation of endogenous proteins such as fibrinogen. A growing body of the literature shows a correlation between increased ICP and metabolic/hormonal changes. The improvement of IIH treated with acetazolamide and/or stenting appears to correlate with the reduction of ICP. Yet the association of this reduction with metabolic changes at the peripheral and central blood level as well as the CSF remains unclear. The search for specific inflammatory, immunological and hormonal biomarkers in patients with IIH and their variation in relation to the ICP should provide a better understanding of its etiology.

Conditions

Idiopathic Intracranial Hypertension

Keywords

Idiopathic intracranial hypertension HII; Intracranial pressure elevation (ICP); Transverse venous sinus stenosis; Cerebral venous stenting; Blood biomarkers

Outcome Measures

Primary Outcomes (1)

• intracranial pressure (ICP) blood biomarker correlation

  The correlation (Pearson's r) between blood biomarkers and ICP measured before and after IIH treatment. Pearson's r will be calculated with a multivariate stepwise linear regression to identify those biomarkers that can explain a change in ICP. The blood biomarkers are extracted from peripheral and central venous blood. The ICP is measured at torcular level. The blood biomarkers include: * Inflammatory markers (pg/mL): * Osteopontin, γ\&β-chain fibrinogen, α1-acid glycoprotein 2 et haptoglobin * Inflammatory cytokines : INFγ, IL-2, IL-10, IL-4, IL-12p70, IL-6, IL-13, IL-8, IL-1β, TNF-α, IL-17, IL-23, IGF-1, TGFβ1 * Chemokines: Fractalkine, SDF-1, CX3CL1, MCP-1, CCL3, CCL5 * BBB integrity markers (pg/mL): S100b, GFAP, Neurofilament light-chain, Neuronal specific enolase, Uch-L1 * Headache associated markers (pg/mL): Calcitonin Gene Related-Peptide, Glucagon-Like Peptide * Hormonal markers (ng/mL): 11β-HSD1, Glucagon-like peptide-1, DHEAS, Leptin, estradiol, and testosterone

  Change over time before (at inclusion) and 3 months after IIH treatment (follow-up)

Secondary Outcomes (6)

• Headache severity

  change over time before (at inclusion) and 3 months after IIH treatment (follow-up)

• Body mass index (BMI)

  change over time before (at inclusion) and 3 months after IIH treatment (follow-up)

• Optic fibre layer (RNF) thickness

  Before (at inclusion) and 3 months after treatment (follow-up)

• Transverse sinus stenosis

  change over time before (at inclusion) and 3 months after IIH treatment (follow-up)

• Cerebral blood flow

  change over time before (at inclusion) and 3 months after IIH treatment (follow-up)

Study Arms (1)

Idiopathic intracranial hypertension (IHH) patient

EXPERIMENTAL

IHH patient with bilateral stenosis of the transversal sinus

Procedure: Blood punction; Procedure: Central blood sampling; Procedure: Intracranial pressure measurement

Interventions

Blood punction PROCEDURE

Peripheral blood sampling (5 ml) at inclusion and 3 months after treatment

Idiopathic intracranial hypertension (IHH) patient

Central blood sampling PROCEDURE

Central blood sampling (2 ml) at inclusion and 3 months after treatment

Idiopathic intracranial hypertension (IHH) patient

Intracranial pressure measurement PROCEDURE

Intracranial pressure measurement at sinus level with micro-catheter at inclusion and 3 months after treatment

Idiopathic intracranial hypertension (IHH) patient

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years and older
• Patients with newly diagnosed untreated HII (following the modified Dandy criteria) with normal CSF composition, abnormal CSF pressure at the lumbar puncture (\>25 cm H2O), and significant pressure gradient at the level of the stenosis (≥8 mmHg)
• Presence of bilateral transverse sinus stenosis (or unilateral with hypoplastic contralateral sinus).

You may not qualify if:

• Allergy to contrast media (nickel, titanium)
• Allergy or contraindication to antiplatelet agents
• Patient on anti-inflammatory treatment
• Chronic inflammatory disease
• History of intracranial venous thrombosis, cerebral hemorrhage, thrombophilia
• History of intracranial tumor
• Fulminant IIH with acute visual loss
• Optic nerve atrophy with papilledema (chronic IIH)
• Female being pregnant, breastfeeding, or planning to become pregnant in the next 3 months
• Major comorbidities with high procedural risk
• Life expectancy \< 6 months
• Adult under guardianship or conservatorship or incapacitated
• Refusal of consent after receiving all necessary information
• Not covered by or not a beneficiary of the French social security system

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

University Hospital of Montpellier - Gui de Chauliac

Montpellier, 34090, France

RECRUITING

Related Publications (13)

• Markey KA, Mollan SP, Jensen RH, Sinclair AJ. Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions. Lancet Neurol. 2016 Jan;15(1):78-91. doi: 10.1016/S1474-4422(15)00298-7. Epub 2015 Dec 8.

  PMID: 26700907 BACKGROUND

• Mollan SP, Aguiar M, Evison F, Frew E, Sinclair AJ. The expanding burden of idiopathic intracranial hypertension. Eye (Lond). 2019 Mar;33(3):478-485. doi: 10.1038/s41433-018-0238-5. Epub 2018 Oct 24.

  PMID: 30356129 BACKGROUND

• Riggeal BD, Bruce BB, Saindane AM, Ridha MA, Kelly LP, Newman NJ, Biousse V. Clinical course of idiopathic intracranial hypertension with transverse sinus stenosis. Neurology. 2013 Jan 15;80(3):289-95. doi: 10.1212/WNL.0b013e31827debd6. Epub 2012 Dec 26.

  PMID: 23269597 BACKGROUND

• Toscano S, Lo Fermo S, Reggio E, Chisari CG, Patti F, Zappia M. An update on idiopathic intracranial hypertension in adults: a look at pathophysiology, diagnostic approach and management. J Neurol. 2021 Sep;268(9):3249-3268. doi: 10.1007/s00415-020-09943-9. Epub 2020 May 27.

  PMID: 32462350 BACKGROUND

• Dhungana S, Sharrack B, Woodroofe N. Cytokines and chemokines in idiopathic intracranial hypertension. Headache. 2009 Feb;49(2):282-5. doi: 10.1111/j.1526-4610.2008.001329.x.

  PMID: 19222599 BACKGROUND

• Zanello SB, Tadigotla V, Hurley J, Skog J, Stevens B, Calvillo E, Bershad E. Inflammatory gene expression signatures in idiopathic intracranial hypertension: possible implications in microgravity-induced ICP elevation. NPJ Microgravity. 2018 Jan 11;4:1. doi: 10.1038/s41526-017-0036-6. eCollection 2018.

  PMID: 29354685 BACKGROUND

• Nicholson P, Brinjikji W, Radovanovic I, Hilditch CA, Tsang ACO, Krings T, Mendes Pereira V, Lenck S. Venous sinus stenting for idiopathic intracranial hypertension: a systematic review and meta-analysis. J Neurointerv Surg. 2019 Apr;11(4):380-385. doi: 10.1136/neurintsurg-2018-014172. Epub 2018 Aug 30.

  PMID: 30166333 BACKGROUND

• Fahmy EM, Rashed LA, Mostafa RH, Ismail RS. Role of tumor necrosis factor-alpha in the pathophysiology of idiopathic intracranial hypertension. Acta Neurol Scand. 2021 Nov;144(5):509-516. doi: 10.1111/ane.13482. Epub 2021 Jun 15.

  PMID: 34131899 BACKGROUND

• Samanci B, Samanci Y, Tuzun E, Altiokka-Uzun G, Ekizoglu E, Icoz S, Sahin E, Kucukali CI, Baykan B. Evidence for potential involvement of pro-inflammatory adipokines in the pathogenesis of idiopathic intracranial hypertension. Cephalalgia. 2017 May;37(6):525-531. doi: 10.1177/0333102416650705. Epub 2016 May 18.

  PMID: 27193133 BACKGROUND

• Hasan-Olive MM, Hansson HA, Enger R, Nagelhus EA, Eide PK. Blood-Brain Barrier Dysfunction in Idiopathic Intracranial Hypertension. J Neuropathol Exp Neurol. 2019 Sep 1;78(9):808-818. doi: 10.1093/jnen/nlz063.

  PMID: 31393574 BACKGROUND

• Eide PK, Eidsvaag VA, Nagelhus EA, Hansson HA. Cortical astrogliosis and increased perivascular aquaporin-4 in idiopathic intracranial hypertension. Brain Res. 2016 Aug 1;1644:161-75. doi: 10.1016/j.brainres.2016.05.024. Epub 2016 May 14.

  PMID: 27188961 BACKGROUND

• Ball AK, Sinclair AJ, Curnow SJ, Tomlinson JW, Burdon MA, Walker EA, Stewart PM, Nightingale PG, Clarke CE, Rauz S. Elevated cerebrospinal fluid (CSF) leptin in idiopathic intracranial hypertension (IIH): evidence for hypothalamic leptin resistance? Clin Endocrinol (Oxf). 2009 Jun;70(6):863-9. doi: 10.1111/j.1365-2265.2008.03401.x. Epub 2008 Sep 2.

  PMID: 18771566 BACKGROUND

• Markey KA, Uldall M, Botfield H, Cato LD, Miah MA, Hassan-Smith G, Jensen RH, Gonzalez AM, Sinclair AJ. Idiopathic intracranial hypertension, hormones, and 11beta-hydroxysteroid dehydrogenases. J Pain Res. 2016 Apr 19;9:223-32. doi: 10.2147/JPR.S80824. eCollection 2016.

  PMID: 27186074 BACKGROUND

MeSH Terms

Conditions

Pseudotumor Cerebri; Intracranial Hypertension

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Federico CAGNAZZO, MD

  University Hospital of Montpellier - Gui de Chauliac

  STUDY DIRECTOR

Central Study Contacts

Federico CAGNAZZO, MD

CONTACT

00334 67 33 75 32; f-cagnazzo@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2023
• First Posted: September 29, 2023
• Study Start: November 27, 2023
• Primary Completion: November 27, 2025
• Study Completion: March 27, 2026
• Last Updated: May 28, 2024

Record last verified: 2024-05

Locations

FR (1)