Efficacy in iNPH Shunting (PENS) Trial

NCT ID: NCT05081128

Last Updated: 2025-05-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-18
• Study Completion Date: 2027-08-31

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.

Conditions

Idiopathic Normal Pressure Hydrocephalus (INPH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Open Shunt Group

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

Group Type: ACTIVE_COMPARATOR

programmable CSF shunt valve

Intervention Type: DEVICE

Brain shunt surgery using a programmable CSF shunt valve

Closed Shunt Group

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.

Group Type: SHAM_COMPARATOR

programmable CSF shunt valve

Intervention Type: DEVICE

Brain shunt surgery using a programmable CSF shunt valve

Interventions

programmable CSF shunt valve

Brain shunt surgery using a programmable CSF shunt valve

Intervention Type: DEVICE

Other Intervention Names

FDA-approved Certas Plus with Siphonguard

Eligibility Criteria

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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Luciano, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Richard Holubkov, PhD

Role: STUDY_DIRECTOR

University of Utah

Locations

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

Indiana University

Indianapolis, Indiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Mayo Clinic

Rochester, Minnesota, 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

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

Countries

United States; Canada; Sweden

References

Luciano MG, Williams MA, Hamilton MG, Katzen HL, Dasher NA, Moghekar A, Hua J, Malm J, Eklund A, Alpert Abel N, Raslan AM, Elder BD, Savage JJ, Barrow DL, Shahlaie K, Jensen H, Zwimpfer TJ, Wollett J, Hanley DF, Holubkov R; PENS Trial Investigators and the Adult Hydrocephalus Clinical Research Network. A Randomized Trial of Shunting for Idiopathic Normal-Pressure Hydrocephalus. N Engl J Med. 2025 Sep 16. doi: 10.1056/NEJMoa2503109. Online ahead of print.

Reference Type: DERIVED

PMID: 40960253 (View on PubMed)

Other Identifiers

1U01NS122764

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PENS

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00305245

Identifier Type: -

Identifier Source: org_study_id