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

Primary Purpose

Idiopathic Normal Pressure Hydrocephalus (INPH)

Status

Completed

Phase

Not Applicable

Locations

International

Study Type

Interventional

Intervention

programmable CSF shunt valve

About this trial

This is an interventional treatment trial for Idiopathic Normal Pressure Hydrocephalus (INPH)

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Johns Hopkins Medicine
University of New Mexico
Cleveland Clinic
University of Washington Medical Center
University of Calgary
Vancouver General Hospital/University of British Colombia
Umeå University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Open Shunt Group

Closed Shunt Group

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

Evaluate the effect of shunting between active and placebo-controlled groups at four months using MoCA test to assess cognition. Scores on the MoCA range from 0 to 30 where lower scores signify greater cognitive impairment.

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

Evaluate the effect of shunting between active and placebo-controlled groups at four months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. The OAB-q SF is scored from 0 to 100 with lower scores indicating worse QOL due to bladder control.

Full Information

NCT ID

NCT03350750

First Posted

November 14, 2017

Last Updated

July 29, 2022

Sponsor

Johns Hopkins University

Collaborators

University of Utah, Integra LifeSciences Corporation

1. Study Identification

Unique Protocol Identification Number

NCT03350750

Brief Title

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

Acronym

PENS

Official Title

A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial: Proof of Concept

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Completed

Study Start Date

May 21, 2018 (Actual)

Primary Completion Date

March 19, 2021 (Actual)

Study Completion Date

May 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

Collaborators

University of Utah, Integra LifeSciences Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

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 four months, the closed shunt group will have zero months of active treatment, and the open shunt group will have four months of active treatment. At four 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 four months of active treatment, unless judged medically necessary by the treating team. Following four months of active treatment, all subjects in each group will have shunt adjustments according to clinical standards at each center.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Idiopathic Normal Pressure Hydrocephalus (INPH)

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

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.

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Open Shunt Group

Arm Type

Active Comparator

Arm Description

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

Arm Title

Closed Shunt Group

Arm Type

Sham Comparator

Arm Description

Intervention Type

Device

Intervention Name(s)

programmable CSF shunt valve

Other Intervention Name(s)

FDA-approved Certas Plus with Siphonguard

Intervention Description

Brain shunt surgery using a programmable CSF shunt valve

Primary Outcome Measure Information:

Title

Change in Gait Velocity

Description

Time Frame

Baseline and 4 months

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and 4 Months

Title

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

Description

Time Frame

Baseline and 4 months

Other Pre-specified Outcome Measures:

Title

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

Description

Evaluate the effect of shunting between active and placebo-controlled groups on change from baseline to four months using ADL/IADL test to assess function. Scores on the Lawton ADL/IADL scale range from 0 to 32 where a lower score indicates less independence in physical and instrumental daily living skills.

Time Frame

Baseline and 4 months

Title

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

Description

Evaluate the effect of shunting between active and placebo-controlled groups at four months using MRS to assess function. Scores on the MRS range from 0 to 6 where higher scores signify increased disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.

Time Frame

Baseline and 4 months

Title

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

Description

Evaluate the effect of shunting between active and placebo-controlled groups at four months using SDMT to assess cognition. Scores on the SDMT range from 0 to 110 where lower scores are associated with reduced psychomotor speed.

Time Frame

Baseline and 4 months

Title

Change in Gait Velocity From Shunt Activation to 8 Months After Active Shunting

Description

Evaluate the clinical improvement of all study participants at eight months of active shunting, using the primary outcome of gait velocity. For patients assigned to Open shunt, active shunting is from Baseline to Month 8 of the study. For patients assigned to Closed Shunt, active shunting is from Month 4 of the study (immediately prior to opening of initially Closed shunt) to Month 12 (i.e., after 8 months of the patient having an open shunt).

Time Frame

Up to 8 months after active shunting

Title

Change in Cognition Using MoCA From Baseline to 8 Months After Active Shunting

Description

Evaluate the clinical improvement of all study participants at eight months of active shunting using MoCA to assess cognition. Scores on the MoCA range from 0 to 30 where lower scores signify greater cognitive impairment.

Time Frame