Normal pressure hydrocephalus MedDRA version: 20.0 Level: LLT Classification code 10020510 Term: Hydrocephalus acquired System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Diacarb
Product Name: Acetazolamide
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Sponsors
Uppsala University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of idiopathic 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 =65 years) yes F.1.3.1 Number of subjects for this age range 56
Exclusion criteria
Exclusion criteria: 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 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 is asked to participate in the study) 13. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the effect of acetazolamide on gait in patients with normal pressure hydrocephalus. ;Secondary Objective: Secondary objectives are to study: • The changes in subjective symptoms and change in life quality over time in patients with normal pressure hydrocephalus treated with acetazolamide. • 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. • The safety profile of and side effects in patients with normal pressure hydrocephalus treated with acetazolamide. • Changes in the concentration of biomarkers in the blood after treatment with acetazolamide. • Changes in the concentration of biomarkers in the cerebrospinal fluid after treatment with acetazolamide. ;Primary end point(s): 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. ;Timepoint(s) of evaluation of this end point: Relative change in gait between visit 1 and 3 is considered the primary endpoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Quality of life assessed by o The EQ-5D-5L self-completion questionnaire o Questionnaires 1-2 that estimate the patient’s own experience of symptoms and side effects, respectively. • The volume of periventricular white matter calculated by volumetric analysis of brain MRI • Cerebral blood flow analysed by arterial spin labeling MRI • Changes in the fluid composition of the brain analysed by synthetic MRI • The total symptomatic change in motor skills, cognition, and continence, assessed using the Swedish iNPH scale • Blood and cerebrospinal fluid biomarkers (neurofilament light chain protein [NFL], amyloid-beta-42, Tau, and glial fibrillary acidic protein [GFAp]) ;Timepoint(s) of evaluation of this end point: MRI performed during the initial visit, and 3 months after start of treatment. Questionnaires are completed: during the initial visit, and during the telephone follow-up at 2-3 weeks, 6-7 weeks, and 3 months after start of treatment, and prior to the shunt surgery, and 3 months after surgery Cognitive tests are performed: at the initial visit, 3 months after start of treatment, prior to shunt surgery, and 3 months after surgery Blood samples for analysis of electrolytes, creatinine, and transaminases collected at: the initial visit, prior to telephone follow-up at 2-3 weeks and 6-7 weeks after start of treatment, 3 months after start of treatment, prior to the shunt surgery, and 3 months after surgery. | — |
Countries
Sweden
Contacts
Public ContactJohan Virhammar
Uppsala University Hospital
Outcome results
None listed