Efficacy in iNPH Shunting (PENS) Trial

Idiopathic Normal Pressure Hydrocephalus (INPH) Clinical Trial

— PENS  

Official title:

A Placebo-Controlled Efficacy in iNPH Shunting (PENS) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05081128
• Other study ID #: IRB00305245
• Secondary ID: 1U01NS122764PENS
• Status: Recruiting
• Phase: N/A
• Start date: May 18, 2022
• Est. completion date: August 2027

Study information

• Verified date: February 2024
• Source: Johns Hopkins University
• Contact: Jessica Wollett
• Phone: 667-306-8141
• Email: penstrial[@]jh.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Placebo-Controlled Efficacy 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 efficacy in iNPH patients.

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 three months, the closed shunt group will have zero months of active treatment, and the open shunt group will have three months of active treatment. At three 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 three months of active treatment, unless judged medically necessary by the treating team. Following the three month visit, all subjects in each group will have shunt adjustments according to clinical standards at each center.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: August 2027
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

1. Age = 60 years; and

2. Diagnosis of iNPH and recommendation for shunt surgery based on the Investigator's clinical judgement based on criteria and testing as described in the iNPH Guidelines;

3. Evans Ratio = 0.30; and

4. One positive supplementary test to include either large volume Lumbar Puncture or extended CSF drainage per institutional standards; and

5. 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

6. Participant has the sensory motor skills, communication skills and understanding to comply with the testing and reporting required in the PENS trial; and

7. Participant is able to give written informed consent.

Exclusion Criteria:

1. Unable to walk 10 meters with or without an assistive device; or

2. Baseline fastest gait velocity (out of three gait trials) >1 m/sec prior to drainage trial and fastest gait velocity improvement is < 30% with or without an assistive device; or

3. Unable to return to the study center for follow up evaluation and shunt programming; or

4. Participant is not medically cleared for shunt surgery per local standards; or

5. 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

6. Prior or existing shunts, endoscopic third ventriculostomy, or any previous surgical intervention for hydrocephalus; or

7. Previous intracranial neurosurgical procedure; or

8. Symptomatic cerebral or cerebellar infarction occurring within 6 months from screening (asymptomatic lacunar infarctions are permitted); or

9. Diagnosis of Parkinsonian syndrome that, in the investigator's judgment, will complicate the outcome evaluation; or

10. 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

11. Diagnosis of dementia disorder where the investigator considers cognition deficit limits participation in the study; or

12. Conditions impairing gait that are considered to be unrelated to hydrocephalus, such as hemiparesis, spasticity, cerebellar ataxia or musculoskeletal and joint disease, which will interfere with gait assessment or the potential for gait improvement.

13. Individuals with contraindication to MRI (e.g., implanted electric and electronic devices, aneurysm clip(s), any metallic fragment or foreign body, coronary and peripheral artery stents, cardiac pacemaker, known claustrophobia, or known/possible pregnancy or breast-feeding) will be excluded according to institutional guidelines.

Related Conditions & MeSH terms

• Hydrocephalus
• Hydrocephalus, Normal Pressure
• Idiopathic Normal Pressure Hydrocephalus (INPH)

Intervention

Device:
• programmable CSF shunt valve
Brain shunt surgery using a programmable CSF shunt valve

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	University of British Columbia	Vancouver
Sweden	Umeå University	Umeå
United States	University of New Mexico Hospital	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of California, Davis	Davis	California
United States	Henry Ford Health System	Detroit	Michigan
United States	Indiana University	Indianapolis	Indiana
United States	University of Southern California	Los Angeles	California
United States	Mount Sinai Health System	New York	New York
United States	New York University Langone Health	New York	New York
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Pacific Neuroscience Institute	Santa Monica	California
United States	University of Washington	Seattle	Washington
United States	University of South Florida	Tampa	Florida
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Canada,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Gait velocity	Evaluation of CSF shunting in iNPH patients through a group comparison of change from baseline at three months between active and placebo-controlled groups, using the primary endpoint of gait velocity (in meters per second).	Baseline and 3 months
Secondary	Change in Gait velocity	Evaluate the change in gait velocity among all study participants between baseline and 9 months of active shunting, using the primary outcome of gait velocity (in meters per second).	Baseline and 9 months
Secondary	Cognition as assessed by the Montreal Cognitive Assessment (MoCA)	Evaluate the effect of shunting between active and placebo-controlled groups at three months using MoCA test to assess cognition. Scores on the MoCA range from 0 to 30, with a score of 26 and higher generally considered normal.	3 months
Secondary	Cognition as assessed by the Montreal Cognitive Assessment (MoCA)	Evaluate the effect of shunting between active and placebo-controlled groups at nine months using MoCA test to assess cognition. Scores on the MoCA range from zero to 30, with a score of 26 and higher generally considered normal.	9 months
Secondary	Bladder Control as assessed by the Overactive Bladder Questionnaire, short form	Evaluate the effect of shunting between active and placebo-controlled groups at three months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. The OAB-q sf consists of three QOL domains: coping, sleep, and emotional/social interaction. All scale scores are transformed to a 0- to 100-point scale, with lower scores indicating greater effect, i.e., worse QOL.	3 months
Secondary	Bladder Control as assessed by the Overactive Bladder Questionnaire, short form	Evaluate the effect of shunting between active and placebo-controlled groups at nine months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. All scale scores are transformed to a 0- to 100-point scale, with lower scores indicating greater effect, i.e., worse QOL.	9 months