Efficacy in iNPH Shunting (PENS) Trial (PENS)

A Placebo-Controlled Efficacy in iNPH Shunting (PENS) Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Normal Pressure Hydrocephalus (INPH)
• Intervention / Treatment: Device: programmable CSF shunt valve

Detailed Description

The primary intervention will be setting the FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve to active (open shunt group)(setting 4)(110 mm H2O) or placebo (closed shunt group)(setting 8)(>400 mm H2O)in a 1:1 ratio. By the time of the primary objective evaluation at three months, the closed shunt group will have zero months of active treatment, and the open shunt group will have three months of active treatment. At three months, shunts for subjects in the closed shunt group will be adjusted to setting 4. To maintain blinding, all patients will be adjusted / mock adjusted to the active setting in a similar fashion. Patients from both groups will not be adjusted before three months of active treatment, unless judged medically necessary by the treating team. Following the three month visit, all subjects in each group will have shunt adjustments according to clinical standards at each center.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jessica Wollett; Phone Number: 667-306-8141; Email: penstrial@jh.edu
• Study Contact Backup: Name: Cristina Camayd-Munoz; Email: cmunoz@jhu.edu

Study Locations

• Canada
  • Vancouver, Canada
    • Recruiting
    • University of British Columbia
    • Contact: Thomas Zwimpfer
    • Principal Investigator: Thomas Zwimpfer, MD
  • Alberta
    • Calgary, Alberta, Canada, AB T2N 1N4
      • Recruiting
      • University of Calgary
      • Contact: Jarred Dronyk; Phone Number: 4039441626; Email: jdronyk@ucalgary.ca
      • Contact: Mark Hamilton, MD; Phone Number: 4039441626; Email: mhamilto@ucalgary.ca
      • Principal Investigator: Mark Hamilton, MD
• Sweden
  • Umeå, Sweden, 901 87
    • Suspended
    • Umea University
• United States
  • California
    • Davis, California, United States, 95616
      • Recruiting
      • University of California, Davis
      • Contact: Janice Wang-Polagruto, PhD, CCRP; Phone Number: 916-551-3244; Email: jfwang@ucdavis.edu
      • Principal Investigator: Kiarash Shahlaie, MD, PhD, FAANS
      • Contact: Gurprit Garcha; Phone Number: 916-551-3243; Email: gkgarcha@ucdavis.edu
    • Los Angeles, California, United States, 90089
      • Recruiting
      • University of Southern California
      • Contact: Darrin Lee, MD
      • Principal Investigator: Darrin Lee
    • Santa Monica, California, United States, 90404
      • Recruiting
      • Pacific Neuroscience Institute
      • Contact: Garni Barkhoudarian, MD; Phone Number: 310-582-7450
      • Principal Investigator: Garni Barkhoudarian, MD
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • University of South Florida
      • Contact: Rachel Karlnoski, PhD; Phone Number: 813-974-8558; Email: karlnosk@usf.edu
      • Principal Investigator: Naomi Abel, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Daniel Barrow, MD; Phone Number: 404-778-4471; Email: daniel.barrow@emory.edu
      • Contact: Yvan Bamps, PhD; Phone Number: 404-778-7673; Email: ybamps@emory.edu
      • Principal Investigator: Daniel Barrow, MD
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Withdrawn
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
      • Contact: Carolyn O'Neil; Phone Number: 317-963-7293; Email: caoneil@iu.edu,
      • Contact: Lauren Snyder; Phone Number: 317-963-1300; Email: lmillar@iu.edu
      • Principal Investigator: Jesse Savage, MD
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
      • Principal Investigator: Mark Luciano
      • Sub-Investigator: Abhay Moghekar
      • Contact: Kallan Dirmeyer; Email: kdirmey1@jhu.edu
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
      • Contact: Rehnuma Newaz; Phone Number: 313-704-5250; Email: rnewaz1@hfhs.org
      • Principal Investigator: Jason Schwalb, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Benjamin Elder, MD
      • Contact: Blake Schleusner; Phone Number: 507-284-5775; Email: Schleusner.blake@mayo.edu
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Withdrawn
      • University of New Mexico Hospital
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Health System
      • Contact: Peter Morgenstern, MD; Phone Number: 212-241-0954; Email: Peter.morgenstern@mountsinai.org
      • Principal Investigator: Peter Morgenstern, MD
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Langone Health
      • Contact: Cathryn Lapierre; Phone Number: 646-501-2762; Email: cathryn.lapierre@nyulangone.org
      • Principal Investigator: Jeffrey Wisoff, MD
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1029
      • Recruiting
      • Wake Forest Baptist Medical Center
      • Contact: Wendy Jenkins, BSN RN, CCRC; Phone Number: 336-716-3842; Email: wejenkin@wakehealth.edu
      • Contact: Kim Hawley; Phone Number: 336.716.4031; Email: khawley@wakehealth.edu
      • Principal Investigator: Daniel Couture, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Jerrod Cook; Phone Number: 216-636-1561; Email: cookj6@ccf.org
      • Contact: Julia Kosco; Phone Number: 216-444-6626; Email: koscoj@ccf.org
      • Principal Investigator: Sean Nagel, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Michael McGehee; Phone Number: 503-494-4988; Email: mcgehee@ohsu.edu
      • Contact: Brian Lothrop; Phone Number: 503.494.4988; Email: lothrop@ohsu.edu
      • Principal Investigator: Ahmed Raslan, MD
  • Texas
    • Dallas, Texas, United States, 75390-8855
      • Recruiting
      • The University of Texas Southwestern Medical Center
      • Contact: Jonathan A. White, MD; Phone Number: 214-648-7912; Email: jonathan.white@utsouthwestern.edu
      • Principal Investigator: Jonathan A. White, MD
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington
      • Contact: Elisa McGee; Phone Number: 206-598-9260; Email: emcgee@uw.edu
      • Principal Investigator: Michael A. Williams, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 60 years; and
2. 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;
3. Evans Ratio ≥ 0.30; and
4. One positive supplementary test to include either large volume Lumbar Puncture or extended CSF drainage per institutional standards; and
5. 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
6. Participant has the sensory motor skills, communication skills and understanding to comply with the testing and reporting required in the PENS trial; and
7. Participant is able to give written informed consent.

Exclusion Criteria:

1. Unable to walk 10 meters with or without an assistive device; or
2. 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
3. Unable to return to the study center for follow up evaluation and shunt programming; or
4. Participant is not medically cleared for shunt surgery per local standards; or
5. 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
6. Prior or existing shunts, endoscopic third ventriculostomy, or any previous surgical intervention for hydrocephalus; or
7. Previous intracranial neurosurgical procedure; or
8. Symptomatic cerebral or cerebellar infarction occurring within 6 months from screening (asymptomatic lacunar infarctions are permitted); or
9. Diagnosis of Parkinsonian syndrome that, in the investigator's judgment, will complicate the outcome evaluation; or
10. 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
11. Diagnosis of dementia disorder where the investigator considers cognition deficit limits participation in the study; or
12. 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.
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Open Shunt Group; 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; Brain shunt surgery using a programmable CSF shunt valve; Other Names: FDA-approved Certas Plus with Siphonguard
Sham Comparator: Closed Shunt Group; 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; Brain shunt surgery using a programmable CSF shunt valve; Other Names: FDA-approved Certas Plus with Siphonguard

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gait velocity	Evaluate the change in gait velocity among all study participants between baseline and 9 months of active shunting, using the primary outcome of gait velocity (in meters per second).	Baseline and 9 months
Cognition as assessed by the Montreal Cognitive Assessment (MoCA)	Evaluate the effect of shunting between active and placebo-controlled groups at three months using MoCA test to assess cognition. Scores on the MoCA range from 0 to 30, with a score of 26 and higher generally considered normal.	3 months
Cognition as assessed by the Montreal Cognitive Assessment (MoCA)	Evaluate the effect of shunting between active and placebo-controlled groups at nine months using MoCA test to assess cognition. Scores on the MoCA range from zero to 30, with a score of 26 and higher generally considered normal.	9 months
Bladder Control as assessed by the Overactive Bladder Questionnaire, short form	Evaluate the effect of shunting between active and placebo-controlled groups at three months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. The OAB-q sf consists of three QOL domains: coping, sleep, and emotional/social interaction. All scale scores are transformed to a 0- to 100-point scale, with lower scores indicating greater effect, i.e., worse QOL.	3 months
Bladder Control as assessed by the Overactive Bladder Questionnaire, short form	Evaluate the effect of shunting between active and placebo-controlled groups at nine months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. All scale scores are transformed to a 0- to 100-point scale, with lower scores indicating greater effect, i.e., worse QOL.	9 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Mark Luciano, MD, PhD, Johns Hopkins University; Study Director: Richard Holubkov, PhD, University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2022
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: IRB00305245; 1U01NS122764 (U.S. NIH Grant/Contract); PENS (Other Identifier: Johns Hopkins University Department of Neurosurgery)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No