Surgical Idiopathic Intracranial Hypertension Treatment Trial

NCT03501966 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: SIGHT1U10EY025990-01A1
• Study Type: interventional
• Target: 7
• Locations: 3 countries
• Sites: 36

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.

Conditions

Idiopathic Intracranial Hypertension

Keywords

headache; idiopathic intracranial hypertension (IIH); shunt; fenestration; acetazolamide; visual loss; diamox

Outcome Measures

Primary Outcomes (1)

• Perimetric Mean Deviation (PMD)

  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

  6 months

Secondary Outcomes (9)

• Treatment Failure

  up to 3 years

• Cerebrospinal Fluid (CSF) Opening Pressure

  6 months

• Papilledema Grade

  6 months

• OCT Retinal Nerve Fiber Layer Thickness

  6 months

• OCT Total Retinal Thickness

  6 months

Study Arms (3)

Acetazolamide including Diet

ACTIVE COMPARATOR

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.

Drug: Acetazolamide

Optic Nerve Sheath Fenestration

ACTIVE COMPARATOR

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.

Procedure: Optic Nerve Sheath Fenestration

Ventriculoperitoneal CSF Shunting

ACTIVE COMPARATOR

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.

Procedure: Ventriculoperitoneal CSF Shunting

Interventions

Acetazolamide DRUG

Medical therapy including diet

Also known as: Diamox, water pill, diuretic

Acetazolamide including Diet

Optic Nerve Sheath Fenestration PROCEDURE

Medical therapy including diet + optic nerve sheath fenestration

Also known as: ONSF

Optic Nerve Sheath Fenestration

Ventriculoperitoneal CSF Shunting PROCEDURE

Medical therapy including diet + ventriculoperitoneal CSF Shunting

Also known as: VPS, CSF Shunt Surgery

Ventriculoperitoneal CSF Shunting

Eligibility Criteria

• Age: 18 Years - 63 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of IIH by modified Dandy criteria (Table 4)
• Age 18 to \<64 years at time of consent
• 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)
• Presence of bilateral papilledema
• 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.

You may not qualify if:

• Able to provide informed consent
• Investigator believes participant is a good candidate for the study, including the probability of returning for follow-up.
• If both eyes meet eligibility criteria at the baseline examination, both will be included in the primary outcome analysis.
• 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
• Visual acuity better than 20/200 (39 or more letters correct)
• 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.
• 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.
• Treatment with topiramate within two months and average cumulative dosage for the preceding month of more than 700 mg per week
• Previous surgery for IIH, including ONSF, CSF shunting, subtemporal decompression, or venous sinus stenting; gastric surgery for obesity is allowed
• 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.
• 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.
• Abnormal blood work-up indicating a medical or systemic condition associated with raised intracranial pressure

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• National Eye Institute (NEI): collaborator
• University of Iowa: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (36)

University of Southern California

Los Angeles, California, 90033, United States

Location

NeuroEyeOrbit Institute

Los Angeles, California, 90048, United States

Location

Stanford University

Palo Alto, California, 94303, United States

Location

University of Colorado - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

The Eye Care Group

Orange, Connecticut, 06477, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Northwestern Medicine

Chicago, Illinois, 60611, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas School of Medicine

Prairie Village, Kansas, 64134, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Bethesda Neurology, LLC

North Bethesda, Maryland, 20852, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University in St. Louis

St Louis, Missouri, 36110, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

State University of New York at Stony Brook

East Setauket, New York, 11733, United States

Location

New York Eye & Ear Infirmary of Mount Sinai

New York, New York, 10003, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Ohio Neuro-Ophthalmology, Orbital Disease and Oculoplastics

Columbus, Ohio, 43214, United States

Location

Dean McGee Eye Institute

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Neuro-Eye Clinical Trials-Houston

Houston, Texas, 77005, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Virginia

Charlottesville, Virginia, 22904, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

University of Calgary

Calgary, Alberta, T2V 1P9, Canada

Location

Sunnybrook Health Science Center

Toronto, Ontario, M4N 3M5, Canada

Location

Rivera, Enrique J

Bayamón, 00961, Puerto Rico

Location

MeSH Terms

Conditions

Pseudotumor Cerebri; Headache; Vision Disorders

Interventions

Acetazolamide; Water; Diuretics

Condition Hierarchy (Ancestors)

Intracranial Hypertension; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Sensation Disorders; Eye Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Natriuretic Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Colleen Bauza
• Organization: Jaeb Center for Health Research

cbauza@jaeb.org

813-975-8690

Study Officials

• Michael Wall, MD

  University of Iowa

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Partially-masked technicians for perimetry, fundus photos, OCT, and refraction/ visual acuity
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: April 18, 2018
• Study Start: February 6, 2019
• Primary Completion: August 28, 2019
• Study Completion: August 28, 2019
• Last Updated: June 16, 2022
• Results First Posted: June 16, 2022

Record last verified: 2020-02

Locations

CA (2); PR (1); US (33)