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

Information

  • Research Project
  • 10279146
  • ApplicationId
    10279146
  • Core Project Number
    U01NS122764
  • Full Project Number
    1U01NS122764-01
  • Serial Number
    122764
  • FOA Number
    PAR-18-422
  • Sub Project Id
  • Project Start Date
    9/30/2021 - 2 years ago
  • Project End Date
    7/31/2026 - 2 years from now
  • Program Officer Name
    CORDELL, JANICE
  • Budget Start Date
    9/30/2021 - 2 years ago
  • Budget End Date
    7/31/2022 - a year ago
  • Fiscal Year
    2021
  • Support Year
    01
  • Suffix
  • Award Notice Date
    9/24/2021 - 2 years ago
Organizations

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

Idiopathic Normal Pressure Hydrocephalus (iNPH) is a reversible form of dementia and gait imbalance in the elderly that has been treated with surgical ventriculoperitoneal shunting (VPS). Although VPS has been performed for decades, the effectiveness of VPS has not been tested in an appropriately run placebo-controlled clinical trial. Due to the lack of data from placebo-controlled trials, skepticism about VPS in the elderly has significantly limited its use. The primary goal of this research proposal is to gather data with the goal of a definitive answer on the question of whether shunt surgery offers a benefit to patients with iNPH. We will accomplish this through a prospective, blinded, randomized placebo-controlled clinical trial that uses a contemporary FDA approved adjustable shunt system. This valve allows a ?virtual off? setting allowing for noninvasive and reversible assignment of patients to treatment with a functioning (active group) or non- functioning (placebo group) shunt. The trial will enroll 100 iNPH patients at 20 sites. Participants selected for shunt surgery will be chosen based on standard and widely used iNPH guidelines. The trial is a delayed treatment paradigm where all 100 patients will receive the same surgery and device, differing only in the initial valve setting (active or placebo). The Primary analysis will be a group comparison of change from baseline in gait velocity at three months after implantation. Secondary analysis will measure balance, cognition, and bladder control. Three months after implantation, all participants in both groups are blindly adjusted to the active setting and followed for 9 months. A secondary goal of the study is to evaluate clinical, imaging, and CSF biomarkers before surgery to identify associations with subsequent shunt response. MR imaging and extended neuropsychological testing are also repeated after shunting to evaluate specific anatomical and cognitive domain changes that may be associated with gait changes. We expect that if we demonstrate the effectiveness of shunting in iNPH we will establish an effective treatment and facilitate an increase in appropriate iNPH shunting. In addition, the study of patient biomarkers associated with successful outcomes will allow future testing of algorithms for more accurate and efficient patient selection. Identification of subgroups of iNPH patients with improvement may also be suggested. Data from this controlled trial can ultimately benefit the 300 to 700 thousand iNPH patients in the US to receive an effective surgical treatment. If data shows that shunting is found to be ineffective in the placebo group, elderly patients will be spared the potential morbidity and cost of an ineffective brain surgery.

IC Name
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
  • Activity
    U01
  • Administering IC
    NS
  • Application Type
    1
  • Direct Cost Amount
    2287963
  • Indirect Cost Amount
    767408
  • Total Cost
    3055371
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    853
  • Ed Inst. Type
    SCHOOLS OF MEDICINE
  • Funding ICs
    NINDS:3055371\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZNS1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    JOHNS HOPKINS UNIVERSITY
  • Organization Department
    NEUROSURGERY
  • Organization DUNS
    001910777
  • Organization City
    BALTIMORE
  • Organization State
    MD
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    212182680
  • Organization District
    UNITED STATES