Clinical trial NCT03350750: A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial
Official title: A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial: Proof of Concept
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Idiopathic Normal Pressure Hydrocephalus (INPH)
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: University of Utah
name: Integra LifeSciences Corporation
First posted: 2017-11-22
Enrollment: 18
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Gait Velocity
timeFrame: Baseline and 4 months
Secondary outcomes:
measure: Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA) Score
timeFrame: Baseline and 4 Months
measure: Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form
timeFrame: Baseline and 4 months
Other outcomes:
measure: Change in Function as Assessed by the Lawton Activities of Daily Living/Independence in Activities of Daily Living (ADL/IADL) Test Score
timeFrame: Baseline and 4 months
measure: Change in Function as Assessed by the Modified Rankin Scale (MRS)
timeFrame: Baseline and 4 months
measure: Change in Cognition as Assessed by the Symbol Digit Modalities Test (SDMT)
timeFrame: Baseline and 4 months
measure: Change in Gait Velocity From Shunt Activation to 8 Months After Active Shunting
timeFrame: Up to 8 months after active shunting
measure: Change in Cognition Using MoCA From Baseline to 8 Months After Active Shunting
timeFrame: Baseline and 8 months after active shunting
measure: Change in Bladder Control From Baseline to 8 Months After Active Shunting
timeFrame: Baseline and 8 months after active shunting
measure: Change in Function Using ADL/IADL From Baseline to 8 Months After Active Shunting
timeFrame: Baseline and 8 months after active shunting
measure: Change in Function Using MRS From Baseline to 8 Months After Active Shunting
timeFrame: Baseline and 8 months after active shunting
measure: Change in Cognition Using SDMT From Baseline to 8 Months After Active Shunting
timeFrame: Baseline and 8 months after active shunting
measure: Number of Patients With Falls
timeFrame: 4 months
measure: Frequency of Adverse Effects
timeFrame: 8 months
measure: Adverse Events
timeFrame: 4 and 8 months of active shunting
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Medicine
state: Maryland
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital/University of British Colombia
state: British Colombia
city: Umeå
country: Sweden
facility: Umeå University
Study officials:
affiliation: Johns Hopkins University
name: Mark Luciano, MD
role: PRINCIPAL_INVESTIGATOR
References: