Treatment of normal pressure hydrocephalus with acetazolamide

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Uppsala

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

25 Sep 2025 → 21 Apr 2026

Decision date (initial)

2024-10-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514828-16-00

EudraCT number

2020-004132-22

ClinicalTrials.gov

NCT04975269

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To examine the effect of acetazolamide on gait in patients with normal pressure hydrocephalus

Secondary objectives 5

1. The changes in subjective symptoms and change in life quality over time in patients with normal pressure hydrocephalus treated with acetazolamide.
2. Changes in the MRI parameters of patients with normal pressure hydrocephalus treated with acetazolamide, with focus on: periventricular white matter hyperintensities, cerebral blood flow, and brain morphology.
3. The safety profile of and side effects in patients with normal pressure hydrocephalus treated with acetazolamide.
4. Changes in the concentration of biomarkers in the blood after treatment with acetazolamide.
5. Changes in the concentration of biomarkers in the cerebrospinal fluid after treatment with acetazolamide.

Conditions and MedDRA coding

Normal pressure hydrocephalus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Diagnosis of idiopatic normal pressure hydrocephalus according to international guidelines
2. Age ≥50 years and ≤82 years
3. Cognitive function with Mini-Mental State Examination > 20 points or cognitive domain of the iNPH scale ≥30 points
4. MRI image for iNPH defined as callosal angle <95 degrees and dilated lateral ventricles or image as in disproportionately subarachnoid space hydrocephalus (DESH)
5. Signed informed consent form

Exclusion criteria 16

1. Exclusion criteria for MRI examination
2. Participation in another medical trial
3. Other disease likely to impact the symptoms of the patient
4. Wheelchair bound or in need of support when walking
5. Reduced kidney function with creatinine GFR < 50
6. Reduced liver function: Prothrombin complex > 1.2 or increased alanine transaminase concentrations in plasma 1.5 times above the upper reference value (women > 1.125 mkat/L; men > 1.65 mkat/L)
7. Known heart failure
8. Low concentrations of electrolytes in blood plasma, or other illness or treatment that may cause significant lowering of electrolyte concentrations according to the investigator
9. Angle-closure glaucoma
10. Allergy to acetazolamide, sulfonamides, or sulfonamide derivatives
11. Treatment with phenytoin, valproate, carbamazepine, lithium, thiazide-diuretics > 25mg/day, acetylsalicylic acid > 100 mg/day, daily use of NSAID or furosemide > 20 mg/day
12. Inability to swallow capsules of the same size as the investigational medicinal products (will be tested using empty capsules when the patient as asked to participate in the study)
13. Average walking time for the three walking tests < 10.5 seconds for men and <11.5 seconds for women
14. Average walking time for the three walking tests > 50 seconds
15. 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
16. Females who are not infertile or females of childbearing potential who do not use highly effective birth control. For females of childbearing potential a negative pregnancy test will be documented before inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The relative change in gait between walking trials is the primary outcome measure. Walking is examined as the sum of time and steps required to walk a distance of 10 meters, timed up-and-go (TUG), and walking backwards for 3 meters

Secondary endpoints 4

1. Quality of life assessed by the EQ-5D-5L self-completion questionnaire and questionnaires 1-2 that estimate the patient's own experience of symptoms and side effects, respectively
2. The volume of periventricular white matter calculated by volumetric analysis of brain MRI
3. The total symptomatic change in motor skills, cognition, and continence, assessed using the Swedish iNPH scale
4. Blood and cerebrospinal fluid biomarkers (neurofilament light chain protein (NFL), amyloid-beta-42, Tau, and glial fibrillary acidic protein (GFAp))

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Uppsala

Sponsor organisation

Region Uppsala

Address

Storgatan 27, Uppsala Domkyrkofors. Uppsala Domkyrkofors.

City

Uppsala

Postcode

753 31

Country

Sweden

Scientific contact point

Organisation

Region Uppsala

Contact name

Johan Virhammar

Public contact point

Organisation

Region Uppsala

Contact name

Johan Virhammar

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications