A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial (PENS)
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| ClinicalTrials.gov Identifier: NCT03350750 |
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Recruitment Status :
Completed
First Posted : November 22, 2017
Results First Posted : May 27, 2022
Last Update Posted : August 2, 2022
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Sponsor:
Johns Hopkins University
Collaborators:
University of Utah
Integra LifeSciences Corporation
Information provided by (Responsible Party):
Johns Hopkins University
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Idiopathic Normal Pressure Hydrocephalus (INPH) | Device: programmable CSF shunt valve | Not Applicable |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 18 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention 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 (Participant, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial: Proof of Concept |
| Actual Study Start Date : | May 21, 2018 |
| Actual Primary Completion Date : | March 19, 2021 |
| Actual Study Completion Date : | May 18, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Hydrocephalus
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 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
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Device: programmable CSF shunt valve
Brain shunt surgery using a programmable CSF shunt valve
Other Name: FDA-approved Certas Plus with Siphonguard |
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Sham Comparator: 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) four months after the procedure.
|
Device: programmable CSF shunt valve
Brain shunt surgery using a programmable CSF shunt valve
Other Name: FDA-approved Certas Plus with Siphonguard |
Primary Outcome Measures :
- 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).
Secondary Outcome Measures :
- Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA) Score [ Time Frame: Baseline and 4 Months ]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.
- Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form [ Time Frame: Baseline and 4 months ]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.
Other Outcome Measures:
- Change in Function as Assessed by the Lawton Activities of Daily Living/Independence in Activities of Daily Living (ADL/IADL) Test Score [ Time Frame: Baseline and 4 months ]Evaluate the effect of shunting between active and placebo-controlled groups on change from baseline to four months using ADL/IADL test to assess function. Scores on the Lawton ADL/IADL scale range from 0 to 32 where a lower score indicates less independence in physical and instrumental daily living skills.
- Change in Function as Assessed by the Modified Rankin Scale (MRS) [ Time Frame: Baseline and 4 months ]Evaluate the effect of shunting between active and placebo-controlled groups at four months using MRS to assess function. Scores on the MRS range from 0 to 6 where higher scores signify increased disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.
- Change in Cognition as Assessed by the Symbol Digit Modalities Test (SDMT) [ Time Frame: Baseline and 4 months ]Evaluate the effect of shunting between active and placebo-controlled groups at four months using SDMT to assess cognition. Scores on the SDMT range from 0 to 110 where lower scores are associated with reduced psychomotor speed.
- Change in Gait Velocity From Shunt Activation to 8 Months After Active Shunting [ Time Frame: Up to 8 months after active shunting ]Evaluate the clinical improvement of all study participants at eight months of active shunting, using the primary outcome of gait velocity. For patients assigned to Open shunt, active shunting is from Baseline to Month 8 of the study. For patients assigned to Closed Shunt, active shunting is from Month 4 of the study (immediately prior to opening of initially Closed shunt) to Month 12 (i.e., after 8 months of the patient having an open shunt).
- Change in Cognition Using MoCA From Baseline to 8 Months After Active Shunting [ Time Frame: Baseline and 8 months after active shunting ]Evaluate the clinical improvement of all study participants at eight months of active shunting using MoCA to assess cognition. Scores on the MoCA range from 0 to 30 where lower scores signify greater cognitive impairment.
- Change in Bladder Control From Baseline to 8 Months After Active Shunting [ Time Frame: Baseline and 8 months after active shunting ]Evaluate the clinical improvement of all study participants at eight months of active shunting using OAB-q test to assess bladder control. The OAB-q SF is scored from 0 to 100 with lower scores indicating worse QOL due to bladder control.
- Change in Function Using ADL/IADL From Baseline to 8 Months After Active Shunting [ Time Frame: Baseline and 8 months after active shunting ]Evaluate the effect of shunting between active and placebo-controlled groups on change from baseline to four months using ADL/IADL test to assess function. Scores on the Lawton ADL/IADL scale range from 0 to 32 where a lower score indicates less independence in physical and instrumental daily living skills.
- Change in Function Using MRS From Baseline to 8 Months After Active Shunting [ Time Frame: Baseline and 8 months after active shunting ]Evaluate the effect of shunting between active and placebo-controlled groups at four months using MRS to assess function. Scores on the MRS range from 0 to 6 where higher scores signify increased disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.
- Change in Cognition Using SDMT From Baseline to 8 Months After Active Shunting [ Time Frame: Baseline and 8 months after active shunting ]Evaluate the clinical improvement of all study participants at eight months of active shunting using SDMT to assess cognition. Scores on the SDMT range from 0 to 110 where lower scores are associated with reduced psychomotor speed.
- Number of Patients With Falls [ Time Frame: 4 months ]Evaluate the effect of shunting between active and placebo-controlled groups at four months by assessing the number of patients with falls.
- Frequency of Adverse Effects [ Time Frame: 8 months ]Evaluate the clinical improvement of all study participants at eight months of active shunting by assessing the frequency of falls, surgical and non-surgical complications, related and unrelated.
- Adverse Events [ Time Frame: 4 and 8 months of active shunting ]Compare adverse events (AEs) in the active versus placebo-controlled group at four months and at eight months of active shunting.
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| Ages Eligible for Study: | 60 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03350750
Locations
| United States, Maryland | |
| Johns Hopkins Medicine | |
| Baltimore, Maryland, United States, 21287 | |
| United States, New Mexico | |
| University of New Mexico | |
| Albuquerque, New Mexico, United States, 87106 | |
| United States, Ohio | |
| Cleveland Clinic | |
| Cleveland, Ohio, United States, 44195 | |
| United States, Washington | |
| University of Washington Medical Center | |
| Seattle, Washington, United States, 98196 | |
| Canada, Alberta | |
| University of Calgary | |
| Calgary, Alberta, Canada, T2N 2T9 | |
| Canada, British Colombia | |
| Vancouver General Hospital/University of British Colombia | |
| Vancouver, British Colombia, Canada, V5Z 1M9 | |
| Sweden | |
| Umeå University | |
| Umeå, Sweden | |
Sponsors and Collaborators
Johns Hopkins University
University of Utah
Integra LifeSciences Corporation
Investigators
| Principal Investigator: | Mark Luciano, MD | Johns Hopkins University |
Study Documents (Full-Text)
Documents provided by Johns Hopkins University:
Documents provided by Johns Hopkins University:
Study Protocol [PDF] May 8, 2020
Statistical Analysis Plan [PDF] May 14, 2018
Informed Consent Form [PDF] November 21, 2019
| Responsible Party: | Johns Hopkins University |
| ClinicalTrials.gov Identifier: | NCT03350750 |
| Other Study ID Numbers: |
IRB00083576 |
| First Posted: | November 22, 2017 Key Record Dates |
| Results First Posted: | May 27, 2022 |
| Last Update Posted: | August 2, 2022 |
| Last Verified: | May 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) |
| Time Frame: | One year after publication of the results of the primary analysis. |
| Access Criteria: | individual participant data (IPD) will be made available to researchers submitting a request for data that includes an analytic plan approved by the Institutional Review Board (IRB) at their institution |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | Yes |
| Device Product Not Approved or Cleared by U.S. FDA: | Yes |
| Product Manufactured in and Exported from the U.S.: | No |
Additional relevant MeSH terms:
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Hydrocephalus Hydrocephalus, Normal Pressure Brain Diseases Central Nervous System Diseases Nervous System Diseases |