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

Idiopathic Normal Pressure Hydrocephalus (INPH) Clinical Trial

— PENS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03350750
• Other study ID #: IRB00083576
• Status: Completed
• Phase: N/A
• Start date: May 21, 2018
• Est. completion date: May 18, 2021

Study information

• Verified date: May 2022
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 18, 2021
• Est. primary completion date: March 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hydrocephalus
• Hydrocephalus, Normal Pressure
• Idiopathic Normal Pressure Hydrocephalus (INPH)

Intervention

Device:
• programmable CSF shunt valve
Brain shunt surgery using a programmable CSF shunt valve

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Vancouver General Hospital/University of British Colombia	Vancouver	British Colombia
Sweden	Umeå University	Umeå
United States	University of New Mexico	Albuquerque	New Mexico
United States	Johns Hopkins Medicine	Baltimore	Maryland
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	Integra LifeSciences Corporation, University of Utah

Countries where clinical trial is conducted

United States,  Canada,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Function as Assessed by the Lawton Activities of Daily Living/Independence in Activities of Daily Living (ADL/IADL) Test Score	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.	Baseline and 4 months
Other	Change in Function as Assessed by the Modified Rankin Scale (MRS)	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.	Baseline and 4 months
Other	Change in Cognition as Assessed by the Symbol Digit Modalities Test (SDMT)	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.	Baseline and 4 months
Other	Change in Gait Velocity From Shunt Activation to 8 Months After Active Shunting	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).	Up to 8 months after active shunting
Other	Change in Cognition Using MoCA From Baseline to 8 Months After Active Shunting	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.	Baseline and 8 months after active shunting
Other	Change in Bladder Control From Baseline to 8 Months After Active Shunting	Evaluate the clinical improvement of all study participants at eight months of active shunting using OAB-q test to assess bladder control. The OAB-q SF is scored from 0 to 100 with lower scores indicating worse QOL due to bladder control.	Baseline and 8 months after active shunting
Other	Change in Function Using ADL/IADL From Baseline to 8 Months After Active Shunting	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.	Baseline and 8 months after active shunting
Other	Change in Function Using MRS From Baseline to 8 Months After Active Shunting	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.	Baseline and 8 months after active shunting
Other	Change in Cognition Using SDMT From Baseline to 8 Months After Active Shunting	Evaluate the clinical improvement of all study participants at eight months of active shunting using SDMT to assess cognition. Scores on the SDMT range from 0 to 110 where lower scores are associated with reduced psychomotor speed.	Baseline and 8 months after active shunting
Other	Number of Patients With Falls	Evaluate the effect of shunting between active and placebo-controlled groups at four months by assessing the number of patients with falls.	4 months
Other	Frequency of Adverse Effects	Evaluate the clinical improvement of all study participants at eight months of active shunting by assessing the frequency of falls, surgical and non-surgical complications, related and unrelated.	8 months
Other	Adverse Events	Compare adverse events (AEs) in the active versus placebo-controlled group at four months and at eight months of active shunting.	4 and 8 months of active shunting
Primary	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	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.	Baseline and 4 Months
Secondary	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.	Baseline and 4 months