Efficacy in iNPH Shunting (PENS) Trial
- Conditions
- Idiopathic Normal Pressure Hydrocephalus (INPH)
- Interventions
- Device: programmable CSF shunt valve
- Registration Number
- NCT05081128
- Lead Sponsor
- Johns Hopkins University
- Brief Summary
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.
- 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 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- Age ≥ 60 years; and
- 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;
- Evans Ratio ≥ 0.30; and
- One positive supplementary test to include either 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.
- Unable to walk 10 meters with or without an assistive device; or
- 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
- 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
- Symptomatic cerebral or cerebellar infarction occurring 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, which will interfere with gait assessment or the potential for gait improvement.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open Shunt Group programmable CSF shunt valve 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 Closed Shunt Group programmable CSF shunt valve 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.
- Primary Outcome Measures
Name Time Method Change in Gait velocity Baseline and 3 months Evaluation of CSF shunting in iNPH patients through a group comparison of change from baseline at three months between active and placebo-controlled groups, using the primary endpoint of gait velocity (in meters per second).
- Secondary Outcome Measures
Name Time Method Cognition as assessed by the Montreal Cognitive Assessment (MoCA) 9 months Evaluate the effect of shunting between active and placebo-controlled groups at nine months using MoCA test to assess cognition. Scores on the MoCA range from zero to 30, with a score of 26 and higher generally considered normal.
Change in Gait velocity Baseline and 9 months Evaluate the change in gait velocity among all study participants between baseline and 9 months of active shunting, using the primary outcome of gait velocity (in meters per second).
Bladder Control as assessed by the Overactive Bladder Questionnaire, short form 9 months Evaluate the effect of shunting between active and placebo-controlled groups at nine months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. All scale scores are transformed to a 0- to 100-point scale, with lower scores indicating greater effect, i.e., worse QOL.
Trial Locations
- Locations (22)
University of California, Davis
🇺🇸Davis, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Pacific Neuroscience Institute
🇺🇸Santa Monica, California, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of New Mexico Hospital
🇺🇸Albuquerque, New Mexico, United States
New York University Langone Health
🇺🇸New York, New York, United States
Mount Sinai Health System
🇺🇸New York, New York, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
The University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of Calgary
🇨🇦Calgary, Alberta, Canada
University of British Columbia
🇨🇦Vancouver, Canada
Umeå University
🇸🇪Umeå, Sweden