Acetazolamide Trial in Normal Pressure Hydrocephalus

NCT04975269 | Completed Phase 2 DMC

• 1 other identifier: NPH-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

A pharmacological treatment to patients with normal pressure hydrocephalus (NPH) is missing. The aim is to investigate if acetazolamide given to patients with NPH improves gait function and study the pathophysiological mechanisms leading to reduced symptoms. Patients will be randomized to acetazolamide or placebo and duration of treatment will be from diagnosis to the day of shunt surgery. Target dose is 500 mg/day. Study design is a double-blind randomized controlled trial and the plan is to include 42-50 patients. The study is investigator-initiated without financial sponsorship from the industry.

Conditions

Idiopathic Normal Pressure Hydrocephalus (INPH)

Keywords

normal pressure hydrocephalus; iNPH; Acetazolamide; Diamox; RCT

Outcome Measures

Primary Outcomes (1)

• Proportional change in gait function

  Gait function is determined by one variable that is calculated as the mean time and number of steps of three different gait tests: 10 meter walking in self chosen speed, timed up and go test (TUG) and 3 m walking backwards. The two fastest attempts of three attempts for each test are documented. The mean time and number of steps of the two fastest attempts for the three tests are calculated to a single variable and the proportional difference between study visits is used as the primary outcome variable.

  Change from baseline gait function immediately after intervention (at time of shunt surgery)

Secondary Outcomes (12)

• Change in idiopathic normal pressure hydrocephalus (iNPH) scale

  Change from baseline iNPH-scale score immediately after intervention (at time of shunt surgery)

• Change in volume of periventricular hyperintensities

  Change from baseline at 3 months

• Change in cerebral blood perfusion

  Change from baseline at 3 months

• Change in quantified CSF flow in cerebral aqueduct

  Change from baseline at 3 months

• Change in parenchymal water content

  Change from baseline at 3 months

Study Arms (2)

Acetazolamide

ACTIVE COMPARATOR

Acetazolamide (active)

Drug: Acetazolamide

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Placebo DRUG

Placebo

Placebo

Acetazolamide DRUG

Target dose: 500 mg / day

Also known as: Diamox

Acetazolamide

Eligibility Criteria

• Age: 50 Years - 82 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of idiopathic normal pressure hydrocephalus according to international guidelines
• Age ≥ 50 years and ≤ 82 years
• Cognitive function with Mini-Mental State Examination \> 20 points or cognitive domain of iNPH scale ≥ 30 points.
• MRI image characteristic of normal pressure hydrocephalus, defined as callosal angle \< 90 degrees and dilated lateral ventricles or pattern of disproportionately enlarged subarachnoid space hydrocephalus (DESH).
• Signed informed consent form

You may not qualify if:

• Participation in another medical trial
• Other disease likely to impact the symptoms of the patient
• Wheelchair user or unable to walk without support
• Reduced kidney function with GFR \< 50
• Reduced liver function (increased INR or alanine transaminase concentrations in plasma elevated more than 1.5 times reference values)
• Known heart failure
• Low concentrations of electrolytes in blood plasma that, according to the investigator, prevents participation in the study
• Angle-closure glaucoma
• Allergy to acetazolamide, sulfonamides, or sulfonamide derivatives
• Treatment with phenytoin, valproate, carbamazepine, lithium, oral anticoagulants, thiazide-diuretics, or acetylsalicylic acid \> 100 mg/day
• Inability to swallow capsules of the same size as the investigational medicinal products (will be tested using empty capsules when the patient is asked to participate in the study)
• Average walking time for the three walking tests \< 10.5 seconds for men and \< 11.5 seconds for women.
• Average walking time for the three walking tests \> 50 seconds
• Inability to comply with the study treatment independently, and a concurrent lack of individuals to help the patient comply with the treatment during the study period

Sponsors & Collaborators

• Uppsala University Hospital: lead
• Uppsala University: collaborator
• Swedish Society for Medical Research: collaborator

Study Sites (1)

Department of Clinical Neurophysiology, Neurosurgery and Neurology, Uppsala University Hospital

Uppsala, Sweden

Location

Related Publications (6)

• Aimard G, Vighetto A, Gabet JY, Bret P, Henry E. [Acetazolamide: an alternative to shunting in normal pressure hydrocephalus? Preliminary results]. Rev Neurol (Paris). 1990;146(6-7):437-9. French.

  PMID: 2399408 BACKGROUND

• Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH. SYMPTOMATIC OCCULT HYDROCEPHALUS WITH "NORMAL" CEREBROSPINAL-FLUID PRESSURE. A TREATABLE SYNDROME. N Engl J Med. 1965 Jul 15;273:117-26. doi: 10.1056/NEJM196507152730301. No abstract available.

  PMID: 14303656 BACKGROUND

• Garcia-Gasco P, Salame Gamarra F, Tenllado Doblas P, Chazarra Talens C. [Complete resolution of chronic hydrocephalus of adult with acetazolamide]. Med Clin (Barc). 2005 Apr 9;124(13):516-7. doi: 10.1157/13073568. No abstract available. Spanish.

  PMID: 15847775 BACKGROUND

• Alperin N, Oliu CJ, Bagci AM, Lee SH, Kovanlikaya I, Adams D, Katzen H, Ivkovic M, Heier L, Relkin N. Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH. Neurology. 2014 Apr 15;82(15):1347-51. doi: 10.1212/WNL.0000000000000313. Epub 2014 Mar 14.

  PMID: 24634454 BACKGROUND

• Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005 Sep;57(3 Suppl):S4-16; discussion ii-v. doi: 10.1227/01.neu.0000168185.29659.c5.

  PMID: 16160425 BACKGROUND

• Hellstrom P, Klinge P, Tans J, Wikkelso C. A new scale for assessment of severity and outcome in iNPH. Acta Neurol Scand. 2012 Oct;126(4):229-37. doi: 10.1111/j.1600-0404.2012.01677.x. Epub 2012 May 16.

  PMID: 22587624 BACKGROUND

MeSH Terms

Conditions

Hydrocephalus, Normal Pressure

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Hydrocephalus; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Johan Virhammar, MD, PhD

  Department of Neuroscience, Uppsala University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Double-blind randomized trial.

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: July 23, 2021
• Study Start: February 17, 2022
• Primary Completion: November 18, 2024
• Study Completion: April 21, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: From publication of the first article from this study, ending 10 years following the last published article from this study.
• Access Criteria: Researchers who provide a methodologically sound proposal can contact the principal investigator of the study.

Locations

SE (1)