Efficacy in iNPH Shunting (PENS) Trial

Johns Hopkins University

Status: Active, not recruiting

Conditions: Idiopathic Normal Pressure Hydrocephalus (INPH)

Treatments: Device: programmable CSF shunt valve

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05081128

1U01NS122764 (U.S. NIH Grant/Contract)

IRB00305245

PENS (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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100 participants in 2 patient groups

Open Shunt Group

Active Comparator group

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

Treatment:

Device: programmable CSF shunt valve

Closed Shunt Group

Sham Comparator group

Description:

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.

Treatment:

Device: programmable CSF shunt valve