Acetazolamide for Treating NPH in Shunt-candidates Patients
Status:
Unknown status
Trial end date:
2019-12-01
Target enrollment:
Participant gender:
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.