Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Surgical Idiopathic Intracranial Hypertension Treatment Trial (SIGHT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03501966
Recruitment Status : Terminated (Low enrollment)
First Posted : April 18, 2018
Last Update Posted : February 11, 2020
Sponsor:
Collaborators:
National Eye Institute (NEI)
University of Iowa
Icahn School of Medicine at Mount Sinai
Information provided by (Responsible Party):
Jaeb Center for Health Research

Tracking Information
First Submitted Date  ICMJE April 10, 2018
First Posted Date  ICMJE April 18, 2018
Last Update Posted Date February 11, 2020
Actual Study Start Date  ICMJE February 6, 2019
Actual Primary Completion Date August 28, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2018)
Perimetric Mean Deviation (PMD) [ Time Frame: 6 months ]
Change from baseline to first of Month 6 (Week 26) or time of treatment failure in PMD (perimetric mean deviation) in eligible eye(s) with the size V stimulus
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2018)
  • Treatment Failure [ Time Frame: up to 3 years ]
    Time from randomization to treatment failure
  • Cerebrospinal Fluid (CSF) Opening Pressure [ Time Frame: 6 months ]
    Change in CSF opening pressure measurement by lumbar puncture
  • Papilledema Grade [ Time Frame: 6 months ]
    Change in papilledema grade
  • OCT Retinal Nerve Fiber Layer Thickness [ Time Frame: 6 months ]
    Change in retinal nerve fiber layer thickness
  • OCT Total retinal thickness [ Time Frame: 6 months ]
    Change in total retinal thickness
  • Visual Acuity (VA) using Early Treatment Diabetic Retinopathy Study (ETDRS) chart [ Time Frame: 6 months ]
    Change in VA scores, determined by baseline VA of better than 20/200 (39 or more letters correct) and worsening indicated by less correct letters
  • Quality of Life (QoL) 36 Item Short Form Health Survey (SF-36v2) [ Time Frame: 6 months ]
    Changes in QoL as measured by responses
  • Quality of Life (QoL) Visual Function Questionnaire (VFQ-25) [ Time Frame: 6 months ]
    Changes in QoL as measured by responses
  • Quality of Life (QoL) 10-item neuro-ophthalmic supplement to the VFQ-25 [ Time Frame: 6 months ]
    Changes in QoL as measured by responses
  • Headaches [ Time Frame: 6 months ]
    Headache Impact Test (HIT-6) Inventory
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Surgical Idiopathic Intracranial Hypertension Treatment Trial
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description

After signing the informed consent form, potential subjects will be assessed for eligibility, including eliciting medical and neurologic history, measurement of best-corrected visual acuity, visual field testing, ophthalmoscopy with optic disc edema grading, physical examination, and Optical Coherence Tomography (OCT). Questionnaires will be completed. Blood will be drawn for complete blood count (CBC), electrolytes, liver function tests, renal function tests, amylase if not done as part of routine care within 4 weeks and a pregnancy test will be performed (women of childbearing potential).

Two visual field examinations using a size V stimulus will need to be performed at the Screening/Baseline Visit. The size V fields will be sent to the Visual Field Reading Center (VFRC) to confirm eligibility or determine that testing must be repeated for the subject.

Eligible individuals will be randomly assigned with equal allocation to one of 3 treatment groups: (1) medical therapy, (2) medical therapy plus ONSF, or (3) medical therapy plus VPS. Acetazolamide should be started on the day of randomization. Surgery should be performed as soon as possible, ideally within 3 days of randomization, but not more than 7 days.

Medical therapy will consist of a low sodium weight loss diet and acetazolamide with or without furosemide. Treatment will start with acetazolamide 2 grams per day, with the dose increased as tolerated up to 4 grams per day. If there is no clinical improvement after 2 weeks of maximal dosage of acetazolamide, furosemide will be started at a dose of 40 mg per day (along with potassium) and titrated up to 160-200 mg per day. Pharmacotherapy will be tapered when there is improvement in the papilledema grade, substantial improvement in the PMD and improvement in symptoms or when there is a safety concern.

The primary outcome is measured at the first of 6 months (26 weeks) or time of treatment failure. During the randomized trial, follow-up visits will occur after weeks 4, 8, 16, and 26 (± 7 days). Safety visits will occur after weeks 1 and 2 (± 4 days). Additional office visits may occur as needed. Phone contacts will occur at 12 and 20 weeks (±7 days).

After the 6-month primary outcome visit, subjects will transition to the Treatment Failure Identification Phase for up to 3 years. Ongoing treatment will continue following the guidelines for the first six months as long as treatment failure criteria are not met at which time treatment will be at the discretion of the Site Investigator. Investigators are urged to employ treatments from another arm of the study before other treatments under these circumstances.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Subjects will be randomly assigned with equal allocation to one of the three treatment groups. Using a permuted block design, randomization will be stratified by PMD (average of 2 size V stimulus tests) in the eligible eye(s) (-6 dB to >-12 dB; -12 dB to >-20 dB; -20 dB to -27 dB). If a subject has two eligible eyes, the average PMD of the two eyes will be used for stratification.
Masking: Single (Outcomes Assessor)
Masking Description:
Partially-masked technicians for perimetry, fundus photos, OCT, and refraction/ visual acuity
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Intracranial Hypertension
Intervention  ICMJE
  • Drug: Acetazolamide
    Medical therapy including diet
    Other Names:
    • Diamox
    • water pill
    • diuretic
  • Procedure: Optic Nerve Sheath Fenestration
    Medical therapy including diet + optic nerve sheath fenestration
    Other Name: ONSF
  • Procedure: Ventriculoperitoneal CSF Shunting
    Medical therapy including diet + ventriculoperitoneal CSF Shunting
    Other Names:
    • VPS
    • CSF Shunt Surgery
Study Arms  ICMJE
  • Active Comparator: Acetazolamide including Diet

    Subjects will use 250 mg tablets of acetazolamide, divided into two doses, taken with meals. Initial dose will be 1,000 mg twice per day and increased per titration schedule (Table 6 in protocol).

    Dietary consultation will include advising subjects to adopt a low sodium weight reduced diet.

    Intervention: Drug: Acetazolamide
  • Active Comparator: Optic Nerve Sheath Fenestration

    Acetazolamide including Diet plus Optic Nerve Sheath Fenestration (ONSF) Subjects will use 250 mg tablets of acetazolamide, divided into two doses, taken with meals. Initial dose will be 1,000 mg twice per day and increased per titration schedule (Table 6 in protocol).

    Dietary consultation will include advising subjects to adopt a low sodium weight reduced diet.

    ONSF performed by qualified, certified orbital surgeon using either a medial or supero-medial lid crease approach. ONSF will be performed in one or both eyes, depending on criteria.

    Intervention: Procedure: Optic Nerve Sheath Fenestration
  • Active Comparator: Ventriculoperitoneal CSF Shunting

    Acetazolamide including Diet plus Ventriculoperitoneal CSF Shunting (VPS) Subjects will use 250 mg tablets of acetazolamide, divided into two doses, taken with meals. Initial dose will be 1,000 mg twice per day and increased per titration schedule (Table 6 in protocol).

    Dietary consultation will include advising subjects to adopt a low sodium weight reduced diet.

    VPS performed by qualified, certified neurosurgeon using a frameless image-guided stereotactic system and positioning a shunt catheter in the lateral ventricle of the cerebral hemisphere not associated with speech. The catheter will be connected to an adjustable valve, and a distal shunt system will be placed in the peritoneal cavity.

    Intervention: Procedure: Ventriculoperitoneal CSF Shunting
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 7, 2020)
16
Original Estimated Enrollment  ICMJE
 (submitted: April 17, 2018)
180
Actual Study Completion Date  ICMJE August 28, 2019
Actual Primary Completion Date August 28, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 criteria.
    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.

Inclusion

  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 abstinence.
    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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 63 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03501966
Other Study ID Numbers  ICMJE SIGHT
1U10EY025990-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jaeb Center for Health Research
Study Sponsor  ICMJE Jaeb Center for Health Research
Collaborators  ICMJE
  • National Eye Institute (NEI)
  • University of Iowa
  • Icahn School of Medicine at Mount Sinai
Investigators  ICMJE
Study Director: Michael Wall, MD University of Iowa
PRS Account Jaeb Center for Health Research
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP