Efficacy in iNPH Shunting (PENS) Trial

NCT05081128 | Active Not Recruiting DMC FDA Device

• 3 other identifiers: IRB003052451U01NS122764PENS
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 17

Brief Summary

The Placebo-Controlled Efficacy in Idiopathic Normal Pressure Hydrocephalus (iNPH) Shunting (PENS) trial is a multi-center blinded, randomized, placebo-controlled design investigation of cerebrospinal fluid (CSF) shunt surgery to study the shunt efficacy in iNPH patients.

Conditions

Idiopathic Normal Pressure Hydrocephalus (INPH)

Outcome Measures

Primary Outcomes (1)

• Change in Gait velocity

  Evaluation of CSF shunting in iNPH patients through a group comparison of change from baseline at three months between active and placebo-controlled groups, using the primary endpoint of gait velocity (in meters per second).

  Baseline and 3 months

Secondary Outcomes (3)

• Cognition as assessed by the Montreal Cognitive Assessment (MoCA)

  Baseline and 3 months

• Bladder Control as assessed by the Overactive Bladder Questionnaire, short form

  Baseline and 3 months

• Balance and Gait as assessed by the Tinetti Score

  Baseline and 3 months

Other Outcomes (3)

• Bladder Control as assessed by the Overactive Bladder Questionnaire, short form

  Baseline and 12 months of active shunting

• Change in Gait velocity

  Baseline and 12 months of active shunting

• Cognition as assessed by the Montreal Cognitive Assessment (MoCA)

  Baseline and 12 months of active shunting

Study Arms (2)

Open Shunt Group

ACTIVE COMPARATOR

FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to active (open shunt group)(setting 4)(110 mm H2O) at time of shunt implantation

Device: programmable CSF shunt valve

Closed Shunt Group

SHAM COMPARATOR

FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to placebo (closed shunt group)(setting 8)(\>400 mm H2O) at time of shunt implantation followed by setting to active (setting 4) (110 mm H2O) three months after the procedure.

Device: programmable CSF shunt valve

Interventions

programmable CSF shunt valve DEVICE

Brain shunt surgery using a programmable CSF shunt valve

Also known as: FDA-approved Certas Plus with Siphonguard

Closed Shunt Group; Open Shunt Group

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 60 years; and
• Diagnosis of iNPH and recommendation for shunt surgery based on the Investigator's clinical judgement based on criteria and testing as described in the iNPH Guidelines;
• Evans Ratio ≥ 0.30; and
• One positive supplementary test to include either large volume Lumbar Puncture or extended CSF drainage per institutional standards; and
• History or evidence of gait impairment (such as decreased step height or length, decreased speed, retropulsion as described in the iNPH Guidelines) duration ≥ 6 months; and
• Participant has the sensory motor skills, communication skills and understanding to comply with the testing and reporting required in the PENS trial; and
• Participant is able to give written informed consent.

You may not qualify if:

• Unable to walk 10 meters with or without an assistive device; or
• Baseline fastest gait velocity (out of three gait trials) \>1 m/sec prior to drainage trial and fastest gait velocity improvement is \< 30% with or without an assistive device; or
• Unable to return to the study center for follow up evaluation and shunt programming; or
• Participant is not medically cleared for shunt surgery per local standards; or
• Secondary NPH. (Prior encephalitis, meningitis, subarachnoid hemorrhage, traumatic brain injury (including concussion) within two years or with brain injury or skull fracture on baseline imaging, brain abscess, brain tumor, obstructive hydrocephalus (including acquired aqueductal stenosis and carcinomatous meningitis); or
• Prior or existing shunts, endoscopic third ventriculostomy, or any previous surgical intervention for hydrocephalus; or
• Previous intracranial neurosurgical procedure; or
• Symptomatic cerebral or cerebellar infarction occurring within 6 months from screening (asymptomatic lacunar infarctions are permitted); or
• Diagnosis of Parkinsonian syndrome that, in the investigator's judgment, will complicate the outcome evaluation; or
• Diagnosis of schizophrenia or any psychiatric diagnosis (including depression) that, in the investigator's judgment, will complicate the outcome evaluation (such as neuroleptic treatment for schizophrenia); or
• Diagnosis of dementia disorder where the investigator considers cognition deficit limits participation in the study; or
• Conditions impairing gait that are considered to be unrelated to hydrocephalus, such as hemiparesis, spasticity, cerebellar ataxia or musculoskeletal and joint disease, which will interfere with gait assessment or the potential for gait improvement.
• Individuals with contraindication to MRI (e.g., implanted electric and electronic devices, aneurysm clip(s), any metallic fragment or foreign body, coronary and peripheral artery stents, cardiac pacemaker, known claustrophobia, or known/possible pregnancy or breast-feeding) will be excluded according to institutional guidelines.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (17)

University of California, Davis

Davis, California, 95616, United States

Location

University of Southern California

Los Angeles, California, 90089, United States

Location

Pacific Neuroscience Institute

Santa Monica, California, 90404, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

Mount Sinai Health System

New York, New York, 10029, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157-1029, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390-8855, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

University of Calgary

Calgary, Alberta, AB T2N 1N4, Canada

Location

University of British Columbia

Vancouver, Canada

Location

Umeå University

Umeå, 901 87, Sweden

Location

Related Publications (1)

• Luciano MG, Williams MA, Hamilton MG, Katzen HL, Dasher NA, Moghekar A, Hua J, Malm J, Eklund A, Alpert Abel N, Raslan AM, Elder BD, Savage JJ, Barrow DL, Shahlaie K, Jensen H, Zwimpfer TJ, Wollett J, Hanley DF, Holubkov R; PENS Trial Investigators and the Adult Hydrocephalus Clinical Research Network. A Randomized Trial of Shunting for Idiopathic Normal-Pressure Hydrocephalus. N Engl J Med. 2025 Dec 4;393(22):2198-2209. doi: 10.1056/NEJMoa2503109. Epub 2025 Sep 16.

  PMID: 40960253 DERIVED

Study Officials

• Mark Luciano, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Richard Holubkov, PhD

  University of Utah

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The primary intervention will be the initiation of the randomized initial shunt valve opening pressure setting to create a delayed treatment group in half of the study patients. Randomization will be to active or placebo (closed) shunt settings. At the time of the standard three-month evaluation, all subjects will be similarly non-invasively adjusted to bring all subjects in both groups to the active setting while maintaining blinding of the subjects. All settings will be verified by the adjusting neurosurgeon.

Study Record Dates

• First Submitted: October 5, 2021
• First Posted: October 18, 2021
• Study Start: May 18, 2022
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: May 8, 2025

Record last verified: 2025-05

Locations

US (14); SE (1); CA (2)