Idiopathic Normal Pressure Hydrocephalus (INPH)PENSNCT03350750
A Placebo-Controlled Effectiveness 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 7 sites in 3 countries.
Trial summary
The Placebo-Controlled Effectiveness 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 effectiveness 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
- 18 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 21 May 2018to 18 May 2021
- 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 based on the Investigator's clinical judgement based on criteria and testing as described in the INPH Guidelines; and
- Evans Ratio ≥ 0.30; and
- One positive supplementary test to include 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, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures.
Who cannot join
- Unable to walk 10 meters with or without an assistive device; or
- Baseline fastest gait velocity>1 m/sec 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
- Current treatment with anticoagulation medications or expected to be on anticoagulation medications in future based on clinician evaluation; or
- Symptomatic cerebral or cerebellar infarction 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.
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
United States4 sites
University of New Mexico
Albuquerque, New Mexico, 87106
Johns Hopkins Medicine
Baltimore, Maryland, 21287
Cleveland Clinic
Cleveland, Ohio, 44195
University of Washington Medical Center
Seattle, Washington, 98196
Canada2 sites
University of Calgary
Calgary, Alberta, T2N 2T9
Vancouver General Hospital/University of British Colombia
Vancouver, British Colombia, V5Z 1M9
About this study
Official title: A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial: Proof of Concept
The Placebo-Controlled Effectiveness 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 effectiveness 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 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.
- 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) four 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 Idiopathic Normal Pressure Hydrocephalus (INPH) patients through a group comparison of improvement from baseline at four months between active and placebo-controlled groups, using the primary endpoint of gait velocity in meters per second (m/s).
Measured: Baseline and 4 months
Secondary outcomes (2)
Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA) Score
Evaluate the effect of shunting between active and placebo-controlled groups at four months using MoCA test to assess cognition. Scores on the MoCA range from 0 to 30 where lower scores signify greater cognitive impairment.
Measured: Baseline and 4 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 four months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. The OAB-q SF is scored from 0 to 100 with lower scores indicating worse QOL due to bladder control.
Measured: Baseline and 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2017
- Study start21 May 2018
- Primary completion19 Mar 2021
- Study completion18 May 2021
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 four-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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Utah, Integra LifeSciences Corporation
- Responsible party
- Sponsor
- Investigators
- Mark Luciano, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03350750
- Sponsor's protocol ID
- IRB00083576
- Acronym
- PENS
- Status last verified
- May 2022
- First submitted
- 14 Nov 2017
- Last updated
- 2 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: After subject enrollment and follow up have been completed, the Data Coordinating Center (DCC) of the study will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be re-coded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers. The DCC will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document. In accordance with policies determined by the investigators and funding sponsors, the releasable database will be provided to users in electronic form.
Publications
Luciano M, Holubkov R, Williams MA, Malm J, Nagel S, Moghekar A, Eklund A, Zwimpfer T, Katzen H, Hanley DF, Hamilton MG; PENS Co-investigators and AHCRN Site PIs. Placebo-Controlled Effectiveness of Idiopathic Normal Pressure Hydrocephalus Shunting: A Randomized Pilot Trial. Neurosurgery. 2023 Mar 1;92(3):481-489. doi: 10.1227/neu.0000000000002225. Epub 2022 Nov 25.
PubMed 36700738
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial: Proof of Concept
- ClinicalTrials.gov ID
- NCT03350750
- Acronym / sponsor ID
- PENS / IRB00083576
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- University of Utah, Integra LifeSciences Corporation
- Study start
- 21 May 2018 (actual)
- Primary completion
- 19 Mar 2021 (actual)
- Study completion
- 18 May 2021 (actual)
- First posted
- 22 Nov 2017 (actual)
- Results
- Posted 27 May 2022
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 Effectiveness 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 effectiveness 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 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.
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 four-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) four 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 based on the Investigator's clinical judgement based on criteria and testing as described in the INPH Guidelines; and
- Evans Ratio ≥ 0.30; and
- One positive supplementary test to include 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>1 m/sec 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 4 months
Evaluation of CSF shunting in Idiopathic Normal Pressure Hydrocephalus (INPH) patients through a group comparison of improvement from baseline at four months between active and placebo-controlled groups, using the primary endpoint of gait velocity in meters per second (m/s).
2 secondary outcomes
Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA) Score
Time frame: Baseline and 4 Months
Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form
Time frame: Baseline and 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36700738Luciano M, Holubkov R, Williams MA, Malm J, Nagel S, Moghekar A, Eklund A, Zwimpfer T, Katzen H, Hanley DF, Hamilton MG; PENS Co-investigators and AHCRN Site PIs. Placebo-Controlled Effectiveness of Idiopathic Normal Pressure Hydrocephalus Shunting: A Randomized Pilot Trial. Neurosurgery. 2023 Mar 1;92(3):481-489. doi: 10.1227/neu.0000000000002225. Epub 2022 Nov 25.
- Individual participant dataSharing planned: Yes. After subject enrollment and follow up have been completed, the Data Coordinating Center (DCC) of the study will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be re-coded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers. The DCC will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document. In accordance with policies determined by the investigators and funding sponsors, the releasable database will be provided to users in electronic form.
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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 principal investigator
Johns Hopkins University
7 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 7 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 2 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 May 2022). 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 4 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 NCT03350750, 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 2 Aug 2022.