A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial

NCT03350750 | Completed Results DMC FDA Device

• 1 other identifier: IRB00083576
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 7

Brief Summary

The Placebo-Controlled Effectiveness 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 effectiveness in iNPH patients.

Conditions

Idiopathic Normal Pressure Hydrocephalus (INPH)

Outcome Measures

Primary Outcomes (1)

• Change in Gait Velocity

  Evaluation of CSF shunting in Idiopathic Normal Pressure Hydrocephalus (INPH) patients through a group comparison of improvement from baseline at four months between active and placebo-controlled groups, using the primary endpoint of gait velocity in meters per second (m/s).

  Baseline and 4 months

Secondary Outcomes (2)

• Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA) Score

  Baseline and 4 Months

• Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form

  Baseline and 4 months

Other Outcomes (12)

• Change in Function as Assessed by the Lawton Activities of Daily Living/Independence in Activities of Daily Living (ADL/IADL) Test Score

  Baseline and 4 months

• Change in Function as Assessed by the Modified Rankin Scale (MRS)

  Baseline and 4 months

• Change in Cognition as Assessed by the Symbol Digit Modalities Test (SDMT)

  Baseline and 4 months

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) four 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 based on the Investigator's clinical judgement based on criteria and testing as described in the INPH Guidelines; and
• Evans Ratio ≥ 0.30; and
• One positive supplementary test to include 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, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures.

You may not qualify if:

• Unable to walk 10 meters with or without an assistive device; or
• Baseline fastest gait velocity\>1 m/sec 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
• Current treatment with anticoagulation medications or expected to be on anticoagulation medications in future based on clinician evaluation; or
• Symptomatic cerebral or cerebellar infarction 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• University of Utah: collaborator
• Integra LifeSciences Corporation: collaborator

Study Sites (7)

Johns Hopkins Medicine

Baltimore, Maryland, 21287, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Washington Medical Center

Seattle, Washington, 98196, United States

Location

University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

Vancouver General Hospital/University of British Colombia

Vancouver, British Colombia, V5Z 1M9, Canada

Location

Umeå University

Umeå, Sweden

Location

Related Publications (1)

• Luciano M, Holubkov R, Williams MA, Malm J, Nagel S, Moghekar A, Eklund A, Zwimpfer T, Katzen H, Hanley DF, Hamilton MG; PENS Co-investigators and AHCRN Site PIs. Placebo-Controlled Effectiveness of Idiopathic Normal Pressure Hydrocephalus Shunting: A Randomized Pilot Trial. Neurosurgery. 2023 Mar 1;92(3):481-489. doi: 10.1227/neu.0000000000002225. Epub 2022 Nov 25.

  PMID: 36700738 DERIVED

Results Point of Contact

• Title: Jessica Wollett
• Organization: Johns Hopkins

jwollet1@jh.edu

6673068141

Study Officials

• Mark Luciano, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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 four-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: November 14, 2017
• First Posted: November 22, 2017
• Study Start: May 21, 2018
• Primary Completion: March 19, 2021
• Study Completion: May 18, 2021
• Last Updated: August 2, 2022
• Results First Posted: May 27, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: One year after publication of the results of the primary analysis.
• Access Criteria: individual participant data (IPD) will be made available to researchers submitting a request for data that includes an analytic plan approved by the Institutional Review Board (IRB) at their institution

Locations

US (4); CA (2); SE (1)