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Operative Procedures vs. Endovascular Neurosurgery for Untreated Pseudotumor Trial (OPEN-UP)

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ClinicalTrials.gov Identifier: NCT02513914
Recruitment Status : Not yet recruiting
First Posted : August 3, 2015
Last Update Posted : April 21, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Pseudotumor cerebri, also called idiopathic intracranial hypertension (IIH), is characterized by elevated intracranial pressure, headache, and if severe, vision loss. IIH is difficult to treat. Medical management may not adequately resolve the symptoms, and surgical management (primarily through cerebrospinal fluid [CSF] shunting) has a high failure rate. Recently, a relationship between IIH and stenosis of the dural venous sinuses (the veins that drain blood from the brain) has been reported. In patients with IIH in whom there is stenosis of one or more dural venous sinuses, placing a stent in the venous sinus may improve patients' objective symptoms (such as visual loss and papilledema) and subjective symptoms (such as headache). This study will determine whether dural venous sinus stenting is as effective as CSF shunting (considered the standard surgical treatment) in treating IIH patients who have moderate vision loss and stenosis of the dural venous sinuses.

Condition or disease Intervention/treatment
Pseudotumor Cerebri Idiopathic Intracranial Hypertension (IIH) Device: Dural Venous Sinus Stenting Device: Cerebrospinal Fluid Shunting

Detailed Description:

Screening evaluation: Screening will include standard-of-care IIH evaluation including general medical and neurological examinations, blood chemistries, complete blood count, prothrombin time (PT),partial thromboplastin time (PTT), and pregnancy test. Ophthalmological evaluation will include visual acuity, pellucid marginal degeneration (PMD), and optical coherence tomography (OCT). Quality of life assessments are Headache Impact Test-6, Short Form Health Survey-36 and Visual Function Questionnaire-25 + Neuro-Ophthalmology supplement tests. Participants must have had a recent (within 6 months of enrollment) magnetic resonance imaging (MRI) of the brain as well as a diagnostic lumbar puncture (including opening pressure, cerebrospinal fluid (CSF) cell count, CSF glucose and CSF protein), both of which are also part of the standard of care for diagnosis of IIH.

Eligible patients will undergo outpatient diagnostic venography within one month of initial IIH evaluation. Under local anesthesia, transfemoral venous access will be obtained and a guide catheter will be placed in the right jugular bulb. A microcatheter (Excelsior SL-10, Stryker Neurovascular) will then be advanced into the dural venous sinuses, and venography will be performed to determine the presence of any dural venous sinus stenosis. Then, blood pressure will be transduced through the microcatheter at the following anatomic locations: Anterior superior sagittal sinus, posterior superior sagittal sinus, bilateral transverse sinuses, bilateral sigmoid sinuses and bilateral jugular bulbs. The venous pressure gradient will be defined as the difference in pressure measurements between the anatomic locations proximal and distal to any stenotic venous sinus segment, or between the transverse and sigmoid sinuses. A pressure gradient of ≥ 8 mmHg is considered sufficient for subsequent randomization. In patients in which pressure gradient is < 8 mmHg, the patient will not be randomized.

Subsequent visits: Once a patient has met eligibility criteria and undergone randomization, treatment will occur within two weeks of the Neuro-Ophthalmology evaluations and within one month of diagnostic venography. Follow-up visits will occur at two weeks, six months and one year after the index procedure.

At two-week follow-up (within one week on either side), patients will undergo neurological and ophthalmological evaluations, OCT, perimetry, and visual acuity testing for safety. While perimetry at this point will not be used for primary outcome analysis, substantial worsening in any of the above measures despite treatment will prompt consideration for treatment failure.

At six-month follow-up, subjects will undergo perimetry for primary outcome analysis, outpatient diagnostic cerebral venography, and pressure measurements identical to that of the screening evaluation (including pressure measurements at all predefined anatomical locations) within four weeks on either side of the six-month target date. Patients will also complete follow-up quality of life questionnaires (HIT-6, SF-36 and VFQ-25 + Neuro-Ophthalmology supplement) The one-year follow-up will include queries regarding interim medical history, headache status, medication usage (specifically details and dose of those agents used to treat IIH or headache), and the number of IIH-related procedures each subject has undergone since the index procedure. Follow-up will occur within four weeks on either side of the one-year target date.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 98 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Operative Procedures vs. Endovascular Neurosurgery for Untreated Pseudotumor Trial (OPEN-UP)
Anticipated Study Start Date : August 2017
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Dural Venous Sinus Stenting
Pt. will undergo pre-treatment with aspirin and clopidogrel. Transfemoral venous access will be obtained (pt. heparinized).Guide catheter will be placed in jugular bulb ipsilateral to dural venous sinus stenosis. Stent will be deployed across stenotic segment. Balloon angioplasty will not be performed unless initial stenosis is not easily traversed with stent. No pressure measurements will be taken during stent placement. Patients will undergo serial physical/neuro exams for 24 hours post-procedure. Daily dual anti-platelet treatment will continue for 6 months after initial procedure, after which clopidogrel will be discontinued and aspirin 81mg daily will be prescribed indefinitely. If significant bilateral venous sinus stenosis is present, stenosis with more severe pressure gradient will be stented. In pt. with bilateral venous sinus stenosis with equivalent pressure gradients, side will be at surgeon's discretion.
Device: Dural Venous Sinus Stenting
See Dural Venous Sinus Stenting arm.
Active Comparator: Cerebrospinal Fluid Shunting
Choice of shunt procedure (ventriculoperitoneal, ventriculoatrial, or lumboperitoneal), catheter laterality, brand and shunt equipment (including shunt catheters and valves), valve settings of programmable shunt valves (when applicable), intrathecal antibiotic administration and the use of stereotactic navigation will be at the discretion of neurosurgeon. Shunt procedures will be performed per the standard of care, under general anesthesia. An optional surgical procedure guidance document will be provided for other sites. Patients will undergo serial physical and neurological examinations for 24 hours post-procedure prior to discharge.
Device: Cerebrospinal Fluid Shunting
See Cerebrospinal Fluid Shunting arm.


Outcome Measures

Primary Outcome Measures :
  1. Perimetric mean deviation (PMD) at six months [ Time Frame: Six months ]
    PMD was chosen as a primary outcome due to its generalizability, test-retest reliability and standardization across centers, as well as its sensitivity to severity and progression of visual symptoms of IIH. Based on previous work by the Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC) investigators, we defined the upper and lower bounds of visual field loss severity for study inclusion as between -8 and -30 dB in the worst-affected eye. The upper limit of -8 dB ensures enough baseline visual loss to consider surgical treatment and allow room for improvement, while the lower limit of -30 dB ensures that patients with severe visual loss unlikely to significantly improve with any treatment would be excluded. PMD will be tested using Swedish Interactive Threshold Algorithm (SITA) standard 24-2 perimetry with stimulus size III.


Secondary Outcome Measures :
  1. Total number of IIH-related surgeries at one year [ Time Frame: One year ]
    The number of revision surgeries includes either additional stenting for any reason in the stent group, shunt revision for any reason in the shunt group, or other IIH procedures such as optic nerve sheath fenestration in either group. The total number of procedures will be assessed at one year from the index procedure.

  2. Resolution of venous stenosis pressure gradient at six months [ Time Frame: Six months ]
    To determine how the venous pressure gradient is related to symptom severity and resolution after treatment, all randomized patients will undergo follow-up diagnostic venography and pressure measurements at six-month follow-up. In patients with bilateral venous sinus stenosis, pressure gradients will be obtained in both the stented and non-stented sinuses.

  3. Papilledema [ Time Frame: Study entry and two-weeks post-operative ]
    Papilledema will be measured by OCT, as it is considered more quantitative than fundus photography or Frisén grading.

  4. Visual acuity [ Time Frame: Study entry, two-weeks post-operative, six months ]
    Corrected visual acuity will be measured using early treatment diabetic retinopathy high-contrast study charts.

  5. Quality of life [ Time Frame: Study entry and six months ]
    Both headache and visual quality of life instruments will be used to assess subjective measures of treatment impact. These include the HIT-6 headache and SF-36 scales for disability assessment, as well as the VFQ-25 questionnaire (plus the 10 question Neuro-Ophthalmology supplement) for visual disability.

  6. Medication usage [ Time Frame: One year ]
    A simple binary choice of reduced or unchanged/increased usage of headache-modifying medications (including narcotic and non-narcotic analgesics and muscle relaxants)


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years old.
  • Diagnosis of Idiopathic Intracranial Hypertension according to the Modified Dandy Criteria.
  • Moderate to severe visual field loss defined by perimetric mean deviation of at least -8 dB but better than -30 dB in the worst eye.
  • Diagnostic cerebral venography demonstrating a pressure gradient of ≥ 8 mmHg across at least one segment of the dural venous sinus as measured during transfemoral cerebral venography
  • Signed informed consent obtained from the patient.

Exclusion Criteria:

  • CSF pressure <20 cm H2O on lumbar puncture.
  • Abnormal CSF analysis such as elevated protein (>60 mg/dL), low glucose (<30 mg/dL), elevated cell count >5 (unless traumatic lumbar puncture).
  • Previous CSF shunt or diversion procedure of any kind, or previous optic nerve sheath fenestration.
  • Uncontrolled second primary headache disorder (e.g. chronic migraine, medication overuse headache).
  • Allergic reaction to radiological iodine contrast agent.
  • Significant renal impairment (serum creatinine >1.5 mg/dL or creatinine clearance <60 mL/min).
  • Contraindication to general anesthesia.
  • Contraindication to aspirin, clopidogrel or other anticoagulants.
  • Presence of a cranial vascular abnormality (arteriovenous malformation, dural arteriovenous fistula, dural venous sinus thrombosis) or other intracranial mass.
  • Presence of a hypercoagulable state such as Factor V Leiden, Protein C or S deficiency or anti-cardiolipin syndrome.
  • Inability to provide reliable and reproducible visual field examinations (>15% false- positive errors and/or failure to maintain fixation for eye monitoring).
  • Previous or ongoing eye disease such as glaucoma or retinopathy.
  • Pre-existing corrected visual acuity worse than 20/200 in the study eye as measured by early treatment diabetic retinopathy high-contrast study charts, without meeting eligible ophthalmological criteria in the contralateral eye.
  • Other pre-existing conditions accounting for optic atrophy that could produce irreversible vision loss in the study eye without meeting eligible ophthalmological criteria for IIH in the contralateral eye.
  • Condition associated with high risk of retinopathy (e.g. type I diabetes).
  • Previously (within the last 2 months) or currently exposed to a drug or substance that may elevate intracranial pressure (e.g. lithium, high-dose vitamin A, tetracyclines, anabolic steroids, chlordecone, amiodarone, diphenylhydantoin, nalidixic acid).
  • Pregnancy.
  • Presence of a physical, mental or social condition that could prevent adequate follow-up such as terminal illness, homelessness, lack of telephone, drug dependency or anticipation of a significant move away from a study site within one year of enrollment.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02513914


Contacts
Contact: Mary Harrigan, RN 602-406-3343 mary.harrigan@dignityhealth.org

Locations
United States, Arizona
St. Joseph's Hospital and Medical Center Suspended
Phoenix, Arizona, United States, 85013
Sponsors and Collaborators
St. Joseph's Hospital and Medical Center, Phoenix
Investigators
Principal Investigator: Felipe C Albuquerque, MD Barrow Neurosurgical Associates
More Information

Responsible Party: Madelon Petersen, Research Clinician, St. Joseph's Hospital and Medical Center, Phoenix
ClinicalTrials.gov Identifier: NCT02513914     History of Changes
Other Study ID Numbers: 15BN045
First Posted: August 3, 2015    Key Record Dates
Last Update Posted: April 21, 2017
Last Verified: April 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No

Keywords provided by Madelon Petersen, St. Joseph's Hospital and Medical Center, Phoenix:
endovascular neurosurgery

Additional relevant MeSH terms:
Intracranial Hypertension
Pseudotumor Cerebri
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases