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Idiopathic Intracranial Hypertension Treatment Trial (IIHTT)

This study has been completed.
Sponsor:
Collaborators:
University of Rochester
University of Iowa
University of California, Davis
Information provided by (Responsible Party):
St. Luke's-Roosevelt Hospital Center
ClinicalTrials.gov Identifier:
NCT01003639
First received: October 28, 2009
Last updated: October 27, 2014
Last verified: May 2012
  Purpose

Idiopathic intracranial hypertension (IIH), also called pseudotumor cerebri, is a disorder of elevated intracranial pressure of unknown cause [Corbett, et al., 1982; Wall, et al., 1991]. Its incidence is 22.5 new cases each year per 100,000 overweight women of childbearing age, and is rising [Garrett, et al., 2004] in parallel with the obesity epidemic. It affects about 100,000 Americans. Most patients suffer debilitating headaches. Because of pressure on the optic nerve (papilledema), 86% have some degree of permanent visual loss and 10% develop severe visual loss [Wall, et al., 1991]. Interventions to prevent loss of sight, all with unproven efficacy, include diet, diuretics such as acetazolamide, repeated spinal taps, optic nerve sheath fenestration surgery, and cerebrospinal fluid (CSF) shunting procedures. The purported goal of these therapies is to lower intracranial pressure; however, it is unclear which treatments work and by what mechanism. None of these strategies has been verified by properly designed clinical trials. Thus, there is confusion, uncertainty, and weak scientific rationales to guide treatment decisions. This trial will study subjects who have mild visual loss from IIH to (1) establish convincing, evidence-based treatment strategies for IIH to restore and protect vision, (2) follow subjects up to 4 years to observe the long-term treatment outcomes and (3) determine the cause of IIH. To meet those aims, the trial will be divided into a 12-month intervention phase and a 3-year observational phase. Subjects are not required to complete the observational phase of the study, but will be asked to do so and consented for the observational phase of the study at the conclusion of the intervention phase (12 months).


Condition Intervention Phase
Idiopathic Intracranial Hypertension
Drug: Acetazolamide
Drug: Placebo
Behavioral: Formal weight loss counselling program
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-blind, Randomized, Placebo-controlled Study of Weight-Reduction and/or Low Sodium Diet Plus Acetazolamide vs Diet Plus Placebo in Subjects With Idiopathic Intracranial Hypertension With Mild Visual Loss

Resource links provided by NLM:


Further study details as provided by St. Luke's-Roosevelt Hospital Center:

Primary Outcome Measures:
  • Perimetric mean deviation change [ Time Frame: 6 Months from baseline ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Papilledema grade on fundus photography [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]

Enrollment: 166
Study Start Date: January 2010
Study Completion Date: January 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Acetazolamide
Acetazolamide given in escalating doses
Drug: Acetazolamide
Subjects will begin with four 250 mg tablets daily. Tablets will be divided among two doses, taken with meals. Beginning on day 7, subjects will increase the dose by 1 pill every week until 16 tablets daily is reached (4 grams acetazolamide or placebo) or side effects prohibit increasing the dosage further. Thus, subjects who are able to tolerate the study medication will reach the maximum dose by day 84.
Other Names:
  • naproxen
  • acetaminophen
  • aspirin
  • ibuprofen
  • codein
  • butalbital
Behavioral: Formal weight loss counselling program
Teleconference, web-based from central location, using site visits and subject self-assessment tools
Other Names:
  • naproxen
  • acetaminophen
  • aspirin
  • ibuprofen
  • codein
  • butalbital
Placebo Comparator: Sugar pill
Given in escalating "dose" (number of pill)
Drug: Placebo
Subjects will begin with four tablets daily. Tablets will be divided among two doses, taken with meals. Beginning on day 7, subjects will increase the dose by 1 pill every week until 16 tablets daily is reached (4 grams acetazolamide or placebo) or side effects prohibit increasing the dosage further. Thus, subjects who are able to tolerate the study medication will reach the maximum dose by day 84.
Other Names:
  • naproxen
  • acetaminophen
  • aspirin
  • ibuprofen
  • codein
  • butalbital
Behavioral: Formal weight loss counselling program
Teleconference, web-based from central location, using site visits and subject self-assessment tools
Other Names:
  • naproxen
  • acetaminophen
  • aspirin
  • ibuprofen
  • codein
  • butalbital

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Diagnosis of IIH by modified Dandy criteria Signs and symptoms of increased intracranial pressure Absence of localizing findings on neurologic examination Absence of deformity, displacement, or obstruction of the ventricular system and otherwise normal neurodiagnostic studies, except for evidence of increased cerebrospinal fluid pressure (>200 mm water). Abnormal neuroimaging except for empty sella turcica, optic nerve sheath enlargement, and smooth-walled non flow-related venous sinus stenosis or collapse106 should lead to another diagnosis Awake and alert No other cause of increased intracranial pressure present
  2. Diagnosis of IIH for 6 weeks or less
  3. Age 18 to 60 years at time of diagnosis
  4. Reproducible visual loss present on automated perimetry (in eye with greatest loss)
  5. Average PMD -2 dB up to -5 dB in the worst eye
  6. Presence of bilateral papilledema
  7. Able to provide informed consent
  8. Women of child-bearing potential must use an acceptable form of birth control during the intervention phase of the study. Acceptable forms include oral contraceptives, transdermal contraceptives,

Exclusion Criteria:

  1. Total treatment of IIH of more than two weeks (except for acetazolamide which is limited to 1 week). For every day on treatment there must be a one-day washout period.
  2. Previous surgery for IIH including optic nerve sheath fenestration, CSF shunting procedures, subtemporal decompression and venous stenting
  3. Previous gastric bypass surgery
  4. Abnormalities on neurologic examination aside from papilledema and its related visual loss or VI nerve paresis
  5. Abnormal CT or MRI scan (intracranial mass, hydrocephalus, dural sinus thrombus or arteriovenous malformation) other than empty sella, unfolded optic nerve sheaths, flattened sclera, or smooth- walled venous stenosis
  6. CSF pressure less than 200 mm water (patients may have repeat CSF pressure measurements if the first is normal or no opening pressure obtained)
  7. Abnormal CSF contents: increased cells: > 5 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 WBC after correction is 5 wbc/mm3 or less- see Operations Manual for calculation) 8. Intraocular pressure currently > 28 mm Hg or > 30 mm Hg at any time in the past 9. Refractive error > +/- 6.00 sphere or > +/- 3.00 cylinder in either eye with the following exceptions: Subjects with myopia of >-6.00 D sphere but less than or equal to - 8.00 D sphere are eligible if 1)there are no abnormalities on ophthalmoscopy or fundus photos 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 subject wears a contact lens for all perimetry examinations with the appropriate correction. If either the Site Investigator or the PRC director (or his designate) decides there are optic fundus abnormalities of myopia that are associated with visual loss, then 9. Subjects with hyperopia of > +6.00 D but less than or equal to

  • 8.00 D sphere 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 PRC director (or his designate) and 2) the subject wears a contact le 10. Other disorders causing visual loss except for refractive error and amblyopia including cells in the vitreous or iritis 11. Optic disc drusen on exam or in previous history 12. Presence of diagnosed untreated obstructive sleep apnea 13. Inability to provide reliable and reproducible visual field examination (failure to maintain fixation using an eye monitoring device, more than 15% false positive errors) 14. Abnormal blood work-up indicating a medical or systemic condition associated with raised ICP 15. Study blood results showing severe anemia, leukopenia or thrombocytopenia, renal failure, or hepatic disease, based on the Site Investigator's judgment 16. Type I diabetes or the presence of diabetic retinopathy 17. Exposure to a drug, substance or disorder that has been associated with elevation of intracranial pressure within 2 months of diagnosis such as lithium, vitamin A, various cyclines (see table in Operations Manual for conditions and drugs) 18. Other condition requiring diuretics, oral, I.V. or injectable steroids or other pressure lowering agents including topiramate (nasal, inhaled, or topical steroids are allowed since the systemic effects are small) 19. Presence of a medical condition such as renal stones that would contraindicate use of the study drug (acetazolamide) 20. Pregnancy or unwillingness for subject of childbearing potential to use contraception during the first year of the study 21. Breastfeeding mothers are excluded from participation unless willing to discontinue breastfeeding by the baseline visit 22. Presence of a physical, mental, or social condition likely to affect follow-up (drug addiction, terminal illness, no telephone, homeless) 23. Anticipation of a move from the site area within six months and unwillingness to return for follow-up at an IIHTT study site 24. Allergy to pupil dilating drops or narrow angles precluding safe dilation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01003639

  Hide Study Locations
Locations
United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Doheny Eye Center, University of Southern California
Los Angeles, California, United States, 90033
United States, Connecticut
The Eye Care Group, PC
Waterbury, Connecticut, United States, 06708
United States, Florida
Bascom Palmer Eye Institute, University of Miami
Miami, Florida, United States, 33136
Neuro-Ophthamology & Balance Disorders Clinic
Tallahassee, Florida, United States, 32308
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Illinois
Peoria, Illinois, United States, 61637
United States, Iowa
Department of Ophthamology and Visual Sciences, University of Iowa
Iowa City, Iowa, United States, 55242
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Louisiana
Louisiana State University Health Sciences Center - Earl K. Long Medical Center
Baton Rouge, Louisiana, United States, 70810
United States, Maryland
Greater Baltimore Medical Center Department Of Ophthamology
Baltimore, Maryland, United States, 21204
Johns Hopkins Universtiy - Wilmer Ophthamological Institute
Baltimore, Maryland, United States, 21287
Bethesda Neurology, LLC
Bethesda, Maryland, United States, 20814
United States, Massachusetts
Massachusetts Eye and Ear Infirmary - Neuro-Ophthamology Service
Boston, Massachusetts, United States, 02114
United States, Michigan
Michigan State University Department of Neurology
East Lansing, Michigan, United States, 48823
William Beaumont Hosptial Research Institute
Royal Oak, Michigan, United States, 48073
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Saint Louis University Eye Institute
Saint Louis, Missouri, United States, 63104
University of St. Louis
St. Louis, Missouri, United States, 63110
United States, New Jersey
New Jersey Medical School/University Physicians Associates of New Jersey
Newark, New Jersey, United States, 07103
United States, New York
The Mount Sinai Medical Center
New York, New York, United States, 10029
Weill Cornell Medical College
New York, New York, United States, 10021
New York Eye and Ear Infirmary
New York City, New York, United States, 10003
University of Rochester - Flaum Eye Institute
Rochester, New York, United States, 14642
Stony Brook University
Stony Brook, New York, United States, 11794
SUNY Upstate Medical University, Neurology Medical Service Group
Syracuse, New York, United States, 13202
United States, North Carolina
Duke Eye Center
Durham, North Carolina, United States, 27710
Raleigh Neurology Associates, PA
Raleigh, North Carolina, United States, 27607
Wake Forrest University Eye Center
Winston Salem, North Carolina, United States, 27157
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43212
United States, Oklahoma
Dean A. McGee Eye Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health & Science University - Casey Eye Institute
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania, Department of Ophthamology
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Universtiy of Houston - University Eye Institute
Houston, Texas, United States, 77204
The Methodist Hospital: Methodist Eye Associates
Houston, Texas, United States, 77030
University of Texas Science Center
San Antonio, Texas, United States, 78229
United States, Utah
University of Utah, John A. Moran Eye Center
Salt Lake City, Utah, United States, 84132
United States, Virginia
University of Virginia - Department of Ophthalmology
Charlottesville, Virginia, United States, 22903
United States, Washington
Swedish Medical Center
Seattle, Washington, United States, 98014
Canada, Alberta
University of Calgary: Rockyview General Hospital
Calgary, Alberta, Canada, T2V 1P9
Canada, Ontario
Queen's University - Hotel Dieu Hospital
Kingston, Ontario, Canada, K7L 5G2
Sponsors and Collaborators
St. Luke's-Roosevelt Hospital Center
University of Rochester
University of Iowa
University of California, Davis
Investigators
Study Director: Michael Wall, MD University of Iowa
  More Information

Additional Information:
No publications provided by St. Luke's-Roosevelt Hospital Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: St. Luke's-Roosevelt Hospital Center
ClinicalTrials.gov Identifier: NCT01003639     History of Changes
Other Study ID Numbers: NORDIC01, 1U10EY017281-01A1, 1U10EY017387-01A1
Study First Received: October 28, 2009
Last Updated: October 27, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by St. Luke's-Roosevelt Hospital Center:
papilledema
vision loss
headache
obesity
women
diplopia
tinnitus

Additional relevant MeSH terms:
Hypertension
Intracranial Hypertension
Pseudotumor Cerebri
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Acetaminophen
Acetazolamide
Aspirin
Ibuprofen
Naproxen
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Anticonvulsants
Antipyretics
Antirheumatic Agents
Carbonic Anhydrase Inhibitors
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Diuretics
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Gout Suppressants
Hematologic Agents

ClinicalTrials.gov processed this record on October 30, 2014