Surgical Idiopathic Intracranial Hypertension Treatment Trial

Not Recruiting

Trial ID: NCT03501966


Randomized trial of adults (≥18 years old) with idiopathic intracranial hypertension and moderate to severe visual loss without substantial recent treatment who are randomly assigned to (1) medical therapy, (2) medical therapy plus ONSF, or (3) medical therapy plus VPS. The primary outcome is visual field mean deviation change at first of Month 6 (26 weeks) or time of treatment failure of the eligible eye(s), followed by a continuation study to assess time to treatment failure. The determination of eligible eye(s) is based on meeting the eligibility criteria at baseline.

Official Title

Randomized Trial of Medical Therapy (MT) vs. MT Plus Optic Nerve Sheath Fenestration vs. MT Plus Ventriculoperitoneal Cerebrospinal Fluid Shunting in Subjects With Idiopathic Intracranial Hypertension and Moderate to Severe Visual Loss

Stanford Investigator(s)

Heather E. Moss, MD, PhD
Heather E. Moss, MD, PhD

Professor of Ophthalmology and of Neurology

Gordon Li, MD
Gordon Li, MD

Professor of Neurosurgery and, by courtesy, of Neurology and of Otolaryngology - Head & Neck Surgery (OHNS)

Andrea Lora Kossler, MD, FACS
Andrea Lora Kossler, MD, FACS

Assoc Professor of Ophthalmology

Shannon Beres, MD
Shannon Beres, MD

Clinical Associate Professor, Neurology Clinical Associate Professor (By courtesy), Ophthalmology

Robert Dodd, MD, PhD
Robert Dodd, MD, PhD

Associate Professor of Neurosurgery, of Radiology and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS)


Inclusion Criteria:

   - Subject Eligibility Criteria Inclusion Criteria

      1. Diagnosis of IIH by modified Dandy criteria (Table 4)

      2. Age 18 to <64 years at time of consent

      3. Age 18 to <61 years at time of diagnosis (time of diagnosis is the time at which
      the patient meets the modified Dandy criteria, usually after the lumbar puncture
      results are reviewed)

      4. Presence of bilateral papilledema

      5. Lumbar puncture within 6 weeks of screening visit or completed as part of
      screening: Opening CSF pressure >250 mmH2O or 200 to 250 mmH2O with at least one
      of the following:

         - Pulse synchronous tinnitus

         - Cranial nerve VI palsy

         - Echography for disc drusen negative and no other disc anomalies mimicking
         disc edema present

         - Magnetic Resonance Venography (MRV) with lateral sinus collapse/stenosis,
         partially empty sella turcica on coronal or sagittal views of MRI, and optic
         nerve sheaths with filled out CSF spaces next to the globe on T2 weighted
         axial MRI scans If the patient was treated with intracranial pressure
         lowering agents (e.g., acetazolamide) prior to obtaining a lumbar puncture,
         the agent(s) must be discontinued for at least 24 hours prior to performing
         the diagnostic lumbar puncture.

      6. At least one eye meeting all eligible eye inclusion criteria and no exclusion

      7. Able to provide informed consent

      8. Investigator believes participant is a good candidate for the study, including
      the probability of returning for follow-up.

   - Eye-Level Eligibility Criteria Subjects must have at least one eye meeting all of the
   inclusion criteria and none of the exclusion criteria.

If both eyes meet eligibility criteria at the baseline examination, both will be included
in the primary outcome analysis.


   1. Visual field loss meeting the following criteria based on two full threshold 24-2 size
   V tests reviewed by the VFRC:

      - PMD from -6 decibel (dB) to -27 dB

      - Reproducible visual loss present on automated perimetry including no more than
      15% false positive response

   2. Visual acuity better than 20/200 (39 or more letters correct)

Exclusion Criteria:

   - Subject Exclusion Criteria Exclusion Criteria

      1. Treatment of IIH within the past 3 months with either (1) the maximally tolerated
      dosage of acetazolamide for at least one week or (2) more than one month of
      acetazolamide with a cumulative dosage of more than 45 grams 'Maximally-tolerated
      dose' is defined as dosage was reached where dosage could not be increased
      further either because of side effects or because a daily total dosage of 4 grams
      per day was reached.

      If individual discontinued acetazolamide in the past due to side effects,
      individual is only eligible if investigator believes that the individual is
      likely to tolerate acetazolamide, as it will be prescribed in the study.

      2. Treatment of IIH within the past 3 months with either (1) the maximally tolerated
      dosage of methazolamide for at least one week or (2) more than one month of
      methazolamide with a cumulative dosage of more than 4.5 grams
      'Maximally-tolerated dose' is defined as dosage was reached where dosage could
      not be increased further either because of side effects or because a daily total
      dosage of 400 mg per day was reached.

      3. Treatment with topiramate within two months and average cumulative dosage for the
      preceding month of more than 700 mg per week

      4. Previous surgery for IIH, including ONSF, CSF shunting, subtemporal
      decompression, or venous sinus stenting; gastric surgery for obesity is allowed

      5. Abnormalities on neurologic examination except for papilledema and its related
      visual loss or cranial nerve VI to VII paresis; if other abnormalities are
      present, the patient will need to be discussed with the Study Director (SD) for
      study entry.

      6. Abnormal CT or MRI scan (intracranial mass, hydrocephalus, dural sinus thrombus,
      or arteriovenous malformation) other than findings known to occur with increased
      intracranial pressure. Abnormalities on MRI that are not known to cause increased
      intracranial pressure are acceptable.

      7. Abnormal CSF contents: increased cells: > 8 cells; elevated protein: > 45 mg%;
      low glucose: < 30 mg% (If the lumbar puncture produces a cell count compatible
      with a traumatic needle insertion, the patient does not need to be excluded if
      the CSF white blood cell count (WBC) after correction is 8 cells/mm3 or less -
      see Manual of Procedures (MOP) for calculation. If > 8 cells or > 45mg% in CSF
      protein are documented in the CSF or calculated after conversion from a traumatic
      lumbar puncture, the patient can be discussed with the Study Director for
      possible inclusion.)

      8. Abnormal blood work-up indicating a medical or systemic condition associated with
      raised intracranial pressure

      9. Diabetes mellitus with diabetic retinopathy

   10. Ingestion of a drug or substance, or presence of a disorder, that has been
      associated with increased intracranial pressure within 2 months of diagnosis,
      such as lithium, vitamin A related products (e.g., Retin-A), or various cyclines
      (see MOP for conditions and drugs)

   11. Laboratory test results showing severe anemia, leukopenia or thrombocytopenia,
      renal failure, or hepatic disease, based on the Site Investigator's judgment

   12. Other condition requiring continued use of oral, I.V. or injectable steroids
      (nasal, inhaled, or topical steroids are allowed since the systemic effects are
      small). Patients with a condition that resulted in recent or current use of
      steroids but may be safely tapered off will be handled on a case-by-case basis
      after discussion with Study Director/co-Director. See Manual of Procedures (MOP)
      for details.

   13. Presence of a medical condition that would contraindicate use of acetazolamide or
      furosemide or significantly increase surgical risk

   14. Pregnancy or unwillingness for a subject of childbearing potential to use
      contraception during the first 6 months of the study Women of childbearing
      potential must use an acceptable form of birth control during the first 6 months
      of the study. Acceptable forms include oral contraceptives, transdermal
      contraceptives, diaphragm, intrauterine devices (IUDs), condoms with spermicide,
      documented surgical sterilization of either the subject or their partner, or

   15. Presence of a physical, mental, or social condition likely to affect follow-up
      (drug addiction, terminal illness, no telephone, homeless)

   16. Anticipation of a move from the site area within six months and unwillingness to
      return for follow-up at a SIGHT study site

   17. Allergy to pupil dilating drops or narrow angles precluding safe dilation

   18. Presence of a condition that contraindicates general anesthesia

   19. Participation in an investigational trial within 30 days of enrollment that
      involved treatment with any systemic drug therapy or therapy that affects the
      eligible eye(s)

   - Eye Level Exclusion Criteria Exclusion

      1. Intraocular pressure currently >28 mm Hg or >30 mm Hg at any time in the past

      2. Refractive error of more than -6.00 or more than +6.00 sphere or more than 3.00
      cylinder with the following exceptions:

         - Eyes with more than 6.00 D of myopia but less than 8.00 D of myopia are
         eligible if: 1) there are no abnormalities on ophthalmoscopy related to
         myopia that are associated with visual loss (such as staphyloma, retinal
         thinning in the posterior pole, or more than mild optic disc tilt), and 2)
         the individual will wear a contact lens for all perimetry examinations with
         the appropriate correction.

         - Eyes with more than 6.00 D of hyperopia but less than 8.00 D of hyperopia
         are eligible if: 1) there is an unambiguous characteristic halo of
         peripapillary edema as opposed to features of a small crowded disc or other
         hyperopic change related to visual loss determined by the Site Investigator
         or the Photographic Reading Center (PRC) Director (or his designate), and 2)
         the individual will wear a contact lens for all perimetry examinations with
         the appropriate correction (which can be corrected for perimetry or with the
         patient's own contact lens with over correction by lens at the perimeter).

      Note: Refractive error exclusion and exceptions refer to sphere not spherical
      equivalent, with cylinder expressed in plus format.

      3. Other disorders causing visual loss except for refractive error and amblyopia,
      including cells in the vitreous or iritis

      4. Large optic disc drusen on exam or known in previous history (small drusen of the
      disc can occur with longstanding papilledema and are allowed if not so numerous
      that investigator determines they are contributing to vision loss)


drug: Acetazolamide

procedure: Optic Nerve Sheath Fenestration

procedure: Ventriculoperitoneal CSF Shunting

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Mariana Nunez