Clinical Trials

Placebo-Controlled Efficacy in Idiopathic Normal Pressure Hydrocephalus (iNPH) Shunting (PENS) Trial

The PENS trial, a clinical study evaluating the effectiveness of surgical cerebrospinal fluid (CSF) shunting for the treatment of idiopathic normal pressure hydrocephalus (iNPH), has now been completed.

iNPH, first described in the 1960s, is a form of dementia that may be reversible with treatment. The PENS trial evaluated ventriculoperitoneal (VP) shunting, a surgical procedure that uses a small tube to drain excess CSF from the brain to another part of the body where it can be absorbed.

This study used an FDA-approved adjustable shunt system with a “virtual off” setting, allowing researchers to non-invasively assign participants to either an active treatment group or a placebo group. The trial followed a delayed treatment design, meaning all participants ultimately received active shunt treatment after the initial 3-month comparison period.

PENS is a multi-institutional, randomized, double-blinded, placebo-controlled clinical trial funded by the National Institute of Neurological Disorders and Stroke (NINDS), with participation from 20 academic medical centers across the United States, Canada, and Sweden.

Initial findings from the trial have now been published: https://www.nejm.org/doi/10.1056/NEJMoa2503109.

For more information, visit penstrial.org or ClinicalTrials.gov Identifier NCT05081128.

You can also read the Hydrocephalus Association’s blog post, highlighting the grant funding that supported this trial.

The PENS Trial was featured on NINDS’ list of Top 10 Neuroscience Advances of 2025. This distinction span basic, translational, and clinical research and highlights breakthroughs that are advancing neuroscience and improving care for people living with neurological conditions. For the hydrocephalus field, this recognition underscores the growing impact of rigorous clinical research aimed at improving diagnosis and treatment for iNPH.