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A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial (PENS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03350750
Recruitment Status : Active, not recruiting
First Posted : November 22, 2017
Last Update Posted : June 4, 2020
Sponsor:
Collaborators:
University of Utah
Integra LifeSciences Corporation
Information provided by (Responsible Party):
Johns Hopkins University

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

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 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
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hydrocephalus

Arm Intervention/treatment
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
Device: programmable CSF shunt valve
Brain shunt surgery using a programmable CSF shunt valve
Other Name: FDA-approved Certas Plus with Siphonguard

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 :
  1. Gait velocity [ Time Frame: 4 months from baseline ]
    Evaluation of CSF shunting in 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


Secondary Outcome Measures :
  1. Gait velocity [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting, using the primary outcome of gait velocity.

  2. Cognition using Montreal Cognitive Assessment (MoCA) [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months using MoCA test to assess cognition

  3. Cognition using Symbol Digit Modalities Test (SDMT) [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months using SDMT to assess cognition

  4. Function using Modified Rankin Scale (MRS) [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months using MRS to assess function

  5. Function using Lawton Activities of Daily Living/Independence in Activities of Daily Living (ADL/IADL) tests [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months using ADL/IADL test to assess function

  6. Bladder Control [ Time Frame: 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

  7. Frequency of adverse events [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months by assessing the frequency of falls, surgical and non-surgical complications, related and unrelated.

  8. Cognition using MoCA [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using MoCA to assess cognition

  9. Cognition using SDMT [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using SDMT to assess cognition

  10. Function using MRS [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using MRS to assess function

  11. Function using ADL/IADL [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using ADL/IADL to assess function

  12. Bladder control [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using OAB-q test to assess bladder control

  13. 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.

  14. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 deficitlimits 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
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United States, Maryland
Johns Hopkins Medicine
Baltimore, Maryland, United States, 21287
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
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Principal Investigator: Mark Luciano, MD Johns Hopkins University
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03350750    
Other Study ID Numbers: IRB00083576
First Posted: November 22, 2017    Key Record Dates
Last Update Posted: June 4, 2020
Last Verified: June 2020
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

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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