U01NS122764

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.

The Johns Hopkins University

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Baltimore, Maryland 212051832 United States

Single Zip Code

NINDS Efficacy Clinical Trials (U01) - Clinical Trial Required (PAR-18-422)

Amendment Since initial award the End Date has been extended from 07/31/26 to 07/31/27 and the total obligations have increased 217% from $3,055,371 to $9,699,809.