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Trial record 26 of 37 for:    idiopathic intracranial hypertension

Acetazolamide for Treating NPH in Shunt-candidates Patients

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ClinicalTrials.gov Identifier: NCT03779594
Recruitment Status : Recruiting
First Posted : December 18, 2018
Last Update Posted : December 18, 2018
Sponsor:
Information provided by (Responsible Party):
Rabin Medical Center

Brief Summary:

Normal pressure hydrocephalus (NPH) consists of a triad of gait disturbance, cognitive deterioration, and urinary incontinence and is characterized by enlarged cerebral ventricles. Current treatment recommendations are based on surgical diversion of Cerebrospinal fluid (CSF), by a ventriculoperitoneal shunt. When patients are appropriately selected, shunting for NPH has a sustained effect in one-half to two-thirds of patients with a reasonable complication rate. However, evidence regarding the efficacy of shunt surgery consists largely of observational studies with relatively short-term follow-up.

With regards to the adverse effects of shunting, even though decreased substantially in recent years, shunt complications are still common. Recent studies report ten to twenty-two percent of serious adverse effects following shunt surgery, mainly subdural hematoma (SDH) requiring surgery, infection, and cerebral infarction or hemorrhage. Most complication occur in the first year after the procedure. Many others suffer from adverse events that considered non-serious, such as postural headache and asymptomatic SDH.

Since shunt complications are common and potentially severe, there is a need for a better way to identify those patients that will likely benefit from shunting, and find alternative treatments for those unwilling or unable to withstand surgery.

Acetazolamide has been shown to reduce the production of CSF in clinical cases of raised intracranial pressure. It is considered the drug of choice for the treatment of idiopathic intracranial hypertension (pseudotumor cerebri). Intuitively, acetazolamide can be effective for the treatment of NPH by reducing the volume of CSF in the brain, and serve as a medical alternative to shunting. Few case reports and small series demonstrated improvement in MRI abnormalities in NPH-patients after administrating the medication.

This open-label study will examine the feasibility and effectiveness of acetazolamide in NPH-diagnosed patients who are shunt-candidates. Patients will be treated from time of diagnosis, and gait and cognition will be evaluated after 2-6 weeks. This trial would possibly pave the way to a larger randomized placebo-controlled trials, and perhaps offer a medical alternative to surgery for elderly patients and for patients for which operation is contraindicated.


Condition or disease Intervention/treatment Phase
Normal Pressure Hydrocephalus Drug: Acetazolamide Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Acetazolamide for Treating NPH in Shunt-candidates Patients: an Open Label Feasibility Trial
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hydrocephalus

Arm Intervention/treatment
Experimental: treatment group
patients who met the inclusion criteria will be allocated to the treatment group, and will receive acetazolamide from time of diagnosis until shunt surgery (2-6 weeks).
Drug: Acetazolamide
Patients will be assign and treated by acetazolamide from time of allocation until surgery (2-6 weeks after treatment initiation). The maximal dose of acetazolamide will be the same dose used to treat glaucoma, considering similarity of patients' characteristics, such as age and polypharmacy. We will start at a low dose of 250 mg once a day, and increase it slowly to a maximal dose of 500 mg twice a day. Dose will be individualized according to side-effects and tolerability. Renal and liver function tests will be performed before initiation of treatment, and will be examined again two weeks after treatment had begun.
Other Name: Diamox




Primary Outcome Measures :
  1. Change from Baseline Gait [ Time Frame: Baseline, week 4 ]

    Change from Baseline gait will be evaluated by the neurosurgery department's physiotherapist, using the timed-up-and-go (TUG) test (measured in seconds, higher values represent a worse outcome).

    Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).


  2. Change from Baseline Balance [ Time Frame: Baseline, week 4 ]

    Change from Baseline balance will be evaluated by the neurosurgery department's physiotherapist, using the TINETTI balance assessment score. (0-28 scale, higher values represent a better outcome).

    Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).



Secondary Outcome Measures :
  1. Change from Baseline concentration function [ Time Frame: Baseline, week 4 ]

    concentration function will be evaluated by the neurosurgery department's neuropsychologist using the color trial test (seconds, higher values represent a worse outcome).

    Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).


  2. Change from Baseline visuospatial function [ Time Frame: Baseline, week 4 ]

    visuospatial function will be evaluated by the neurosurgery department's neuropsychologist using the clock drawing test (0-10 scale, higher values represent a better outcome).

    Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).


  3. Change from Baseline verbal fluency [ Time Frame: Baseline, week 4 ]

    verbal fluency will be evaluated by the neurosurgery department's neuropsychologist using the verbal fluency test (Controlled Oral Word Association Test, number of words in one minute, higher values represent a better outcome).

    Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).



Other Outcome Measures:
  1. adverse effects [ Time Frame: week 2-6 ]
    All adverse effects that may be attributed to the treatment will be recorded



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Included will be subjects with a probable diagnosis of NPH. The diagnosis will be based primarily on presence of gait impairment plus at least one other impairment in urinary symptoms, cognition impairment or both.

  1. Are 50 years old or older.
  2. Patients who meet the criteria for NPH based on:

    • A typical personal history.
    • A typical brain imaging on head CT or MRI.
    • Normal lumbar puncture findings excluding other conditions.
    • Exclusion of other more likely diagnosis.
  3. Patients who underwent large-volume spinal tap and subsequently improved clinically by at least 10% in gait function or cognition.

Exclusion Criteria:

  • Cirrhosis or marked liver disease or dysfunction.
  • Severe renal disease or dysfunction.
  • Acidosis.
  • Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation.
  • Decreased sodium and/or potassium levels.
  • Adrenocortical insufficiency.
  • Patients with cognitive impairment who will not be able to give informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03779594


Contacts
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Contact: Gilad Kenan, MD 97289779181 giladankori@gmail.com
Contact: Yosi Laviv, MD YossiL2@clalit.org.il

Locations
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Israel
Rabin Medical Center Recruiting
Petah Tikva, Israel, 49100
Contact: Gilad Kenan, MD    528457654    giladankori@gmail.com   
Principal Investigator: Yosi Laviv, MD         
Sub-Investigator: Idan Levitan, MD         
Sponsors and Collaborators
Rabin Medical Center
Investigators
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Principal Investigator: Yosi Laviv, MD Rabin Medical Center

Publications:

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Responsible Party: Rabin Medical Center
ClinicalTrials.gov Identifier: NCT03779594     History of Changes
Other Study ID Numbers: 0597-18
First Posted: December 18, 2018    Key Record Dates
Last Update Posted: December 18, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Rabin Medical Center:
NPH
Acetazolamide

Additional relevant MeSH terms:
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Hydrocephalus
Hydrocephalus, Normal Pressure
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Acetazolamide
Anticonvulsants
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Physiological Effects of Drugs