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 16, 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

  Show 41 Study Locations
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 16, 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:
Pseudotumor Cerebri
Hypertension
Intracranial Hypertension
Vascular Diseases
Cardiovascular Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Acetazolamide
Acetaminophen
Ibuprofen
Naproxen
Aspirin
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Cardiovascular Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on October 19, 2014