Clinical trial NCT04032379: Diagnostic and Prognostic Biomarkers of Idiopathic Intracranial Hypertension
Official title: Diagnostic and Prognostic Biomarkers of Idiopathic Intracranial Hypertension
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Benign Intracranial Hypertension
Lead sponsor: Danish Headache Center
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
First posted: 2019-07-25
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All admitted or out-patient referrals where IIH is suspected. Patients will be identified and included consecutively once there is a clinical suspicion of IIH, if they wish to participate. Most often IIH will be suspected in a typical patient (female, child-bearing age, overweight) with either bilateral papiledema and normal neuro-imaging, high ICP by lumbar puncture or a new headache with associated visual disturbances or pulsatile tinnitus.

All hospitals in the Capital Region of Denmark and the Southern Region of Denmark can participate and refer patients.

Brief summary: Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology, primarily affecting overweight females of childbearing age. Typically, patients experience headache and visual symptoms due to increased intracranial pressure (ICP) and papilledema. The diagnosis is difficult, and outcomes vary from no sequelae to blindness or chronic headaches. No clear prognostic indicators exist. Treatment consists of medication, weight loss, and possibly surgical intervention.There is an unmet need of defining biomarkers with prognostic or diagnostic value and defining predictors of a poor outcome.

This project is a prospective, population-based cohort study including clinical data and a biobank (blood samples and cerebrospinal fluid).

The investigator's primary aim is to identify biomarkers of diagnostic or prognostic value and to create a clinical IIH database. The clinical database will answer questions about patient characteristics at baseline and during follow-up, identify predictors of outcome, and help create a standardized programme for follow-up and

Detailed description: This study is a multicenter, prospective, population-based cohort study with consecutive inclusion of patients in which the diagnosis of IIH is suspected. This study is carried out in collaboration between the Danish Headache Center, Rigshospitalet-Glostrup, and the Neurological Department at Odense University Hospital.

Patients are eligible for inclusion into the study if:

1. IIH is suspected
2. \> 18 years old and able to provide written informed consent.

At baseline included patients will have:

A.) Medical history B.) Neurological, ophthalmological and general medical examination C.) Relevant neuro-imaging D.) Blood samples and lumbar puncture F.) Evaluation by other specialist, including neuro-psychologists, if appropriate.

Subsequently patients are divided into three sub-groups according to revised Friedmann criteria:

1. Certain IIH or IIH-WOP
2. Suspected, but unconfirmed, IIH
3. IIH ruled out

Patients are followed at a headache center and by neuro-ophthalmologist according to standard clinical practice.

Eligibility criteria: Inclusion Criteria:

1. Able to and willing to provide informed consent
2. More than 18 years of age
3. Suspicion of IIH (based on clinical evaluation by neurologist or opthalmologist)

Exclusion Criteria:

1.) Unable to consent (e.g. language, mental retardation).

Primary outcomes:
measure: Biomarkers of IIH (diagnostic and prognostic)
timeFrame: 2 years
measure: Visual status at conclusion of study
timeFrame: 2 years
measure: Visual status at conclusion of study
timeFrame: 2 years
measure: Visual status at conclusion of study
timeFrame: 2 years
measure: Headache status at conclusion of study
timeFrame: 2 years
measure: Biomarkers of IIH (diagnostic and prognostic)
timeFrame: 2 years
Secondary outcomes:
measure: Baseline characteristics related to poor outcome
timeFrame: 1 year
measure: Results of neuropsychological evaluations
timeFrame: 1 year
measure: Treatment and follow-up
timeFrame: 3 years
measure: Baseline characteristics related to IIH diagnosis
timeFrame: 2 years
measure: Weight change in a standard care program
timeFrame: 2 years
measure: Diagnostic criteria and their use in the clinical setting
timeFrame: 2 years
measure: Clinical markers related to disease activity
timeFrame: 2 years
measure: Development of IIH or IIHWOP in patients with borderline elevated ICP not fulfilling diagnostic criteria at baseline
timeFrame: 2 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: The Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup
state: Glostrup
city: Odense
country: Denmark
facility: Odense University Hospital, Department of Neurology
state: Region Syddanmark
Study officials:
affiliation: The Danish Headache Center, Rigshospitalet-Glostrup
name: Rigmor Jensen, M.D., Dr.Med.
role: STUDY_DIRECTOR
affiliation: Odense University Hospital
name: Dagmar Beier, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol. 1988 Aug;45(8):875-7. doi: 10.1001/archneur.1988.00520320065016.
citation: Wall M, Kupersmith MJ, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, Katz DM, Keltner JL, Schron EB, McDermott MP; NORDIC Idiopathic Intracranial Hypertension Study Group. The idiopathic intracranial hypertension treatment trial: clinical profile at baseline. JAMA Neurol. 2014 Jun;71(6):693-701. doi: 10.1001/jamaneurol.2014.133.
citation: Yri HM, Jensen RH. Idiopathic intracranial hypertension: Clinical nosography and field-testing of the ICHD diagnostic criteria. A case-control study. Cephalalgia. 2015 Jun;35(7):553-62. doi: 10.1177/0333102414550109. Epub 2014 Sep 16.
citation: Yri HM, Ronnback C, Wegener M, Hamann S, Jensen RH. The course of headache in idiopathic intracranial hypertension: a 12-month prospective follow-up study. Eur J Neurol. 2014 Dec;21(12):1458-64. doi: 10.1111/ene.12512. Epub 2014 Jul 29.
citation: Yri HM, Fagerlund B, Forchhammer HB, Jensen RH. Cognitive function in idiopathic intracranial hypertension: a prospective case-control study. BMJ Open. 2014 Apr 8;4(4):e004376. doi: 10.1136/bmjopen-2013-004376.
citation: Digre KB, Nakamoto BK, Warner JE, Langeberg WJ, Baggaley SK, Katz BJ. A comparison of idiopathic intracranial hypertension with and without papilledema. Headache. 2009 Feb;49(2):185-93. doi: 10.1111/j.1526-4610.2008.01324.x.
citation: Peng KP, Fuh JL, Wang SJ. High-pressure headaches: idiopathic intracranial hypertension and its mimics. Nat Rev Neurol. 2012 Dec;8(12):700-10. doi: 10.1038/nrneurol.2012.223. Epub 2012 Nov 20.
citation: Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013 Jul;33(9):629-808. doi: 10.1177/0333102413485658. No abstract available.
citation: Nielsen HH, Beck HC, Kristensen LP, Burton M, Csepany T, Simo M, Dioszeghy P, Sejbaek T, Grebing M, Heegaard NH, Illes Z. The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study. PLoS One. 2015 Oct 13;10(10):e0139659. doi: 10.1371/journal.pone.0139659. eCollection 2015.