Idiopathic Normal Pressure Hydrocephalus (INPH)PENSNCT05081128
Efficacy in iNPH Shunting (PENS) Trial
A study testing programmable CSF shunt valve in people with Idiopathic Normal Pressure Hydrocephalus (INPH), run by Johns Hopkins University at 17 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Idiopathic Normal Pressure Hydrocephalus (INPH)
- What is being tested?
- programmable CSF shunt valve
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 17 sitesin 3 countries
- Study dates
- 18 May 2022to 24 Feb 2026
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
17 sites in 3 countries.
17 sites in 3 countries
United States14 sites
Emory University
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21287
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390-8855
University of California, Davis
Davis, California, 95616
Indiana University
Indianapolis, Indiana, 46202
University of Southern California
Los Angeles, California, 90089
New York University Langone Health
New York, New York, 10016
Mount Sinai Health System
New York, New York, 10029
Oregon Health & Science University
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
Pacific Neuroscience Institute
Santa Monica, California, 90404
University of Washington
Seattle, Washington, 98195
University of South Florida
Tampa, Florida, 33612
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157-1029
Canada2 sites
University of Calgary
Calgary, Alberta, AB T2N 1N4
University of British Columbia
Vancouver
About this study
Official title: A Placebo-Controlled Efficacy in iNPH Shunting (PENS) Trial
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.
Read the 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.
- Being tested
- programmable CSF shunt valve
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
programmable CSF shunt valveDevice
Also called FDA-approved Certas Plus with Siphonguard
Brain shunt surgery using a programmable CSF shunt valve
| Study group | Role | What they receive |
|---|---|---|
| Open Shunt Group | Active comparator | 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 Receives: Device: programmable CSF shunt valve |
| Closed Shunt Group | Sham comparator | 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. Receives: Device: programmable CSF shunt valve |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Gait Velocity
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).
Measured: Baseline and 3 months
Secondary outcomes (3)
Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA)
Evaluate the effect of shunting between active and placebo-controlled groups at three months using MoCA test to assess cognition. Scores on the MoCA range from 0 to 30, with a score of 26 and higher generally considered normal.
Measured: Baseline and 3 months
Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form
Evaluate the effect of shunting between active and placebo-controlled groups at three months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. Total score range 0- to 100, with lower score indicating greater effect, i.e., worse QOL.
Measured: Baseline and 3 months
Change in Balance and Gait as Assessed by the Tinetti Score
Evaluate the effect of shunting between active and placebo-controlled groups at three months using Tinetti Score to assess balance and gait. Scores on the Tinetti range from 0 to 28. The higher the score the better the gait and balance performance.
Measured: Baseline and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2021
- Study start18 May 2022
- Primary completion24 Feb 2026
- Study completion24 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Normal Pressure Hydrocephalus (INPH)Studies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 three-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.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Luciano, MD, PhD, Principal investigator, Johns Hopkins UniversityRichard Holubkov, PhD, Study director, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05081128
- Sponsor's protocol ID
- IRB00305245
- Other IDs
- 1U01NS122764, PENS
- Acronym
- PENS
- Status last verified
- Aug 2026
- First submitted
- 5 Oct 2021
- Last updated
- 27 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
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 Dec 4;393(22):2198-2209. doi: 10.1056/NEJMoa2503109. Epub 2025 Sep 16.
PubMed 40960253
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled Efficacy in iNPH Shunting (PENS) Trial
- ClinicalTrials.gov ID
- NCT05081128
- Acronym / sponsor ID
- PENS / IRB00305245
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 18 May 2022 (actual)
- Primary completion
- 24 Feb 2026 (actual)
- Study completion
- 24 Feb 2026 (actual)
- First posted
- 18 Oct 2021 (actual)
- Results
- Posted 27 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- 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 three-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.
| Arm | Type | Receives |
|---|---|---|
| Open Shunt Group | Active comparator | Device: programmable CSF shunt valveFDA-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 | Sham comparator | Device: programmable CSF shunt valveFDA-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. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| programmable CSF shunt valveAlso: FDA-approved Certas Plus with SiphonguardBrain shunt surgery using a programmable CSF shunt valve | Device | Closed Shunt Group, Open Shunt Group |
Primary outcome
Change in Gait Velocity
Time frame: 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).
3 secondary outcomes
Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA)
Time frame: Baseline and 3 months
Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form
Time frame: Baseline and 3 months
Change in Balance and Gait as Assessed by the Tinetti Score
Time frame: Baseline and 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40960253Luciano 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 Dec 4;393(22):2198-2209. doi: 10.1056/NEJMoa2503109. Epub 2025 Sep 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Luciano, MD, PhD principal investigator
Johns Hopkins University
Richard Holubkov, PhD study director
University of Utah
17 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing programmable CSF shunt valve in people with Idiopathic Normal Pressure Hydrocephalus (INPH), run by Johns Hopkins University at 17 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Canada, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Gait Velocity (time frame: Baseline and 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05081128, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.