Clinical Trial: Operative Procedures vs. Endovascular Neurosurgery for Untreated Pseudotumor Trial

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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

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.

Detailed Summary:

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
Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Current Primary Outcome: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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)


Original Secondary Outcome: Same as current

Information By: St. Joseph's Hospital and Medical Center, Phoenix

Dates:
Date Received: July 30, 2015
Date Started: August 2017
Date Completion: December 2022
Last Updated: April 19, 2017
Last Verified: April 2017