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

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.

Inclusion Criteria:

- Age ≥ 65 years; and

- Diagnosis of INPH based on clinical criteria and testing as described in the INPH
Guidelines;2 and

- One positive supplementary test whether infusion test, large volume lumbar puncture
(LP) or extended cerebrospinal fluid (CSF) drainage;3 and

- Duration of gait impairment ≥ 6 months.

- Patient has the understanding and communication skills to comply with the testing and
reporting required in the PENS trial.

Exclusion Criteria:

- Unable to walk 10 meters with or without an assistive device; or

- Baseline gait velocity >1 m/sec. with or without an assistive device; or

- Unable to return to the study center for follow up evaluation and shunt programming;
or

- Patient is not medically cleared for shunt surgery per local standards; or

- Secondary NPH. (Prior encephalitis, meningitis, subarachnoid hemorrhage, traumatic
brain injury (including concussion), 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

- Large cerebral or cerebellar infarction (asymptomatic lacunar infarctions are
permitted); or

- Hemiparesis, cerebellar signs or neurological deficits (e.g., cervical or lumbar
myelopathy, previous stroke) precluding gait assessment; or

- Diagnosis of Parkinsons disease; or

- Diagnosed clinical depression; or

- Diagnosis of schizophrenia or any psychiatric diagnosis which in the clinician's
judgment will complicate the outcome evaluation; or

- Sensory or functional deficit (e.g., uncorrectable severe visual or hearing
impairment) that does not allow full clinical evaluation; or

- Patient has a known cause of cognitive impairment from an established diagnosis such
as Alzheimers Disease; or

- Patient has a MOCA score of <18 taken at the initial screening; or

- Conditions impairing gait that are considered to be unrelated to hydrocephalus, such
as hemiparesis, spasticity, cerebellar ataxia or musculoskeletal and joint disease.