Surgical Idiopathic Intracranial Hypertension Treatment Trial (SIGHT)

This study is no longer enrolling

What is Idiopathic Intracranial Hypertension (IIH)?

Idiopathic Intracranial Hypertension or IIH, also called pseudotumor cerebri, is a disorder of increased intracranial pressure of unknown causes. IIH is a medical term used when pressure in the fluid surrounding the brain is higher than normal. Click here for more in depth information about IIH.

If you or someone you know has IIH and worsening vision, you could potentially be eligible to participate in the SIGHT study. If you know you've have IIH, reading further may help you better understand the disorder.  This page will give you more information about the SIGHT treatment trial that is currently recruiting patients with prior IIH in one or both eyes and have progressive vision loss.

What do we already know about IIH treatments?

When vision loss from Idiopathic Intracranial Hypertension (IIH) is moderate to severe, several medications and surgical treatments can be used. Although each of these treatments can be effective, experts are still not sure which treatment works best. Most Neuro-Ophthalmologist will opt for one of two surgical treatments, Optic Nerve Sheath Fenestration of the worse eye or Ventricular Shunting (VPS), fearing delay will lead to progressive vision loss and permanent vision deficits.

What is the SIGHT study?

The investigators of the Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC) Network previously have identified a manageable course of treatment through the success of the Idiopathic Intracranial Hypertension treatment trial (IIHTT). A combination of high dose acetazolamide and weight management can improve vision in patients with mild visual field loss. Based on the success of the IIHTT, the investigators of NORDIC designed the Surgical Intracranial Hypertension Treatment Trial (SIGHT) study. This clinical trial will compare medical therapy with surgical therapies in patients with IIH, who have moderate to severe visual loss to provide the highest level of evidence to determine the best treatment strategy for these individuals at high risk for developing blindness.

Who is doing the SIGHT study?

The SIGHT study being done by a network of doctors who are a part of the Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC). The Jaeb Center for Health Research is coordinating the study. The study is being funded by the National Eye Institute of the National Institutes of Health. The study currently has 36 clinical sites participating in the SIGHT in the United States and Canada. The contact information for the clinical sites is available at the following: https://clinicaltrials.gov/ct2/show/NCT03501966

Potential patients can easily and rapidly be assessed for eligibility. It is very important that patients be evaluated prior to being on medication. And if possible, we highly recommend a potential patient doing the spinal tap at the clinical site.

What is the purpose of this study?

The NORDIC pilot data and literature review show that the three study treatments could be effective for patients with moderate to severe visual loss in IIH. Some experts think that surgical outcomes are best when the intervention is done early in the patient’s course while others refer for surgery only when medical treatment fails. There is considerable disagreement about when to intervene with a treatment at any given stage of IIH. In a disease that can cause progressive and permanent visual loss, the results of an unbiased randomized controlled trial will provide the evidence that clinicians need to guide these treatment decisions. The purpose of the SIGHT study is to find which treatment works best to reduce or reverse visual loss in people with IIH.

What are the general requirements to participate in the study?

In general, to take part in this study, you must:

  • have IIH with moderate to severe visual loss in one or both eyes

Also, you must not:

  • be currently taking certain medications to treat IIH, including corticosteroids, topiramate, and diuretics (other than furosemide)
  • have had previous surgery for IIH
  • have any treatments for IIH outside of the study, such as weight loss surgery, during the first six months of the study
  • be pregnant

If you are nursing a child, please speak with your doctor to discuss breastfeeding during the study. 

How do I participate?

If you think you or an individual you know fit the criteria and are interested in finding out more, you should see a doctor to be evaluated.  On the following website, under “Contacts and Locations,” you can look for the contact information of a doctor nearest you: https://clinicaltrials.gov/ct2/show/NCT03501966

What are the main inclusion and exclusion criteria’s for the SIGHT study?

 Below is a list of main exclusion and inclusion criteria for the SIGHT study. Interested patients are highly recommended to contact a local medical site to find out more information and how to get involved in the trial.

1. Main Inclusion Criteria

  • Diagnosis of IIH by modified Dandy criteria:  symptoms and signs of increased intracranial pressure in an alert patient. Normal neuroimaging except for signs of increased pressure and high CSF pressure with normal CSF contents. No other cause of high pressure present
  • Age 18 - <64 years
  • Moderate to severe visual field loss
  • Presence of bilateral papilledema

2. Main Exclusion Criteria

  • CSF pressure <200 mm water or abnormal contents
  • Other disorders causing visual loss except for refractive error and amblyopia
  • Inability to provide reliable and reproducible visual field exams
  • Abnormal blood work-up indicating a medical or systemic condition associated with raised ICP
  • Type I diabetes or diabetic retinopathy
  • Recent exposure to a drug, substance or disorder that is associated with intracranial hypertension
  • Some cases with prior treatment of IIH
  • Other condition requiring oral, I.V. or injectable steroids
  • Pregnancy or unwillingness for subject to use contraception during the first 6-months of the study

 

Additional IIH Background

What is Idiopathic Intracranial Hypertension (IIH)?

Idiopathic Intracranial Hypertension or IIH, also called pseudotumor cerebri, is a disorder of increased intracranial pressure of unknown causes. IIH is a medical term used when pressure in the fluid surrounding the brain is higher than normal. The incidence of IIH is rising with the obesity epidemic, with about 22.5 new cases each year per 100,000 overweight women of childbearing age. Although several risk factors such as obesity, weight and female gender have been identified. The relationship between these risk factors and the cause of the disorder is unknown. Because of the pressure on the optic nerve, swelling of the optic nerve head develops papilledema, approximately 86% have some type of visual disturbance and 10% develop severe visual loss. The loss of visual field may be rapid, progressive, and severe. If untreated, and sometimes even with treatment, blindness can occur.

What are the stages of IIH?

Idiopathic intracranial hypertension has four stages based on severity of vision loss. The first stage, (20% of IIH patients) show signs of papilledema and symptoms, but no visual field loss. The second stage (40% of IIH cases), the target for IIHTT study, is characterized by mild visual field defects and prompts effective intervention. The third stage (30% of cases), a target for the SIGHT, is characterized by moderate visual loss. Stage three patients have symptomatic vision loss and current thinking, without class I or II evidence, suggests that aggressive intervention is required to prevent blindness. In the fourth stage (10% of cases), also a target for the SIGHT, severe visual loss occurs, which can worsen rapidly to blindness.

What are the current treatment options for IIH?

Medical therapies for IIH include diet, acetazolamide, and furosemide, are the interventions usually employed for the first two stages of IIH. The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) demonstrated that acetazolamide-plus-diet led to a statistically significant improvement in vision and significant improvements in papilledema grade, CSF pressure, and quality of life measures at 6 months compared to placebo-plus-diet in patients with mild visual loss. Surgical treatments, such as ONSF and CSF shunting, with or without medical therapy, are commonly employed in the third and fourth stages of IIH. Below are details for each type of medical and surgical intervention for IIH.

1. Medical Therapy is usually employed for the first two stages of IIH.

  • Acetazolamide
  • Diet/Weight Loss
  • Furosemide (Lasix) has been used in IIH patients are allergic to or intolerant of acetazolamide. Furosemide reportedly can lower intracranial pressure. Furosemide commonly causes hypokalemia requiring supplemental potassium.

2. Surgical Therapy in IIH – CSF Shunting and Optic Nerve Decompression Procedures

        I.  Optic Nerve Sheath Fenestration (ONSF)

  • ONSF consists of either creating a window or making a series of slits in the optic nerve dural sheath just behind the globe.
  • This treatment has been used for patients with progressive visual loss, and over 50% of patients have post-operative headache relief.
  • Although ONSF appears to be helpful in the short term for visual loss, the long term benefit is unknown and whether the surgically created opening remains open.

       II. CSF Shunting procedures

  • Various shunting procedures have been employed for IIH, but the safest and most accurately assessed method is stereotactic ventricular plural shunt (VPS). In the past, CSF shunting procedure was used for patients with failed medical therapy.
  • Case series document efficacy in preserving vision in most cases, but a shunt failure rate of approximately 40% and the need for shunt revisions were common.

*Recent data and analysis and extrapolating to 2015, estimate 2500 CSF shunt surgeries per year at a cost of about $38,500 per patient, and 250 ONSF’s at $23,000, surgical costs for IIH are estimated at $102 million per year so it is imperative that we obtain high quality evidence of its efficacy.

         III. Venous Sinus Stenting

  • Transverse venous sinus stenoses are a common finding on magnetic resonance venography in patients with IIH, possibly due to external compression of the transverse venous sinus from the increased intracranial pressure. This could produce a pressure gradient between the proximal and distal portions of the transverse venous sinus leading to impaired CSF absorption and further elevation of intracranial pressure (ICP). The venous stenoses often resolve when ICP is reduced by lumbar puncture or shunting, implying that the stenosis is not the cause of IIH. Several uncontrolled case series reported that transverse venous sinus stenting was an effective treatment for IIH. 

*Given the potential for serious permanent complications, we elected not to include this as a study treatment until further unbiased data are collected.