NCT03350750: PENS

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

Completed NA Results posted Last updated 2 August 2022

What this trial tests

NA trial testing programmable CSF shunt valve in Idiopathic Normal Pressure Hydrocephalus (INPH) in 18 participants. Completed in 18 May 2021.

Timeline

21 May 2018

Primary endpoint
19 March 2021

18 May 2021

Quick facts

Lead sponsor	Johns Hopkins University
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	18
Start date	21 May 2018
Primary completion	19 March 2021
Estimated completion	18 May 2021
Sites	7 locations across Sweden, Canada, United States

Drugs / interventions tested

• programmable CSF shunt valve

Conditions studied

• Idiopathic Normal Pressure Hydrocephalus (INPH) — all drugs for Idiopathic Normal Pressure Hydrocephalus (INPH) →

Sponsor

Johns Hopkins University

Who can join

60 and older, any sex, with Idiopathic Normal Pressure Hydrocephalus (INPH). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Gait Velocity Primary · 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).

Group	Value	95% CI
Open Shunt Group	0.28	± 0.284
Closed Shunt Group	0.04	± 0.167

Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA) Score Secondary · 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.

Group	Value	95% CI
Open Shunt Group	-0.13	± 3.643
Closed Shunt Group	1.63	± 1.598

Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form Secondary · 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.

Group	Value	95% CI
Open Shunt Group	-23.3	± 19.89
Closed Shunt Group	2.1	± 17.81

Change in Function as Assessed by the Lawton Activities of Daily Living/Independence in Activities of Daily Living (ADL/IADL) Test Score Secondary · 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.

Group	Value	95% CI
Open Shunt Group	-5.7	± 6.73
Closed Shunt Group	1.4	± 3.89

Change in Function as Assessed by the Modified Rankin Scale (MRS) Secondary · 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.

Group	Value	95% CI
Open Shunt Group	-0.88	± 1.126
Closed Shunt Group	-0.13	± 0.641

Change in Cognition as Assessed by the Symbol Digit Modalities Test (SDMT) Secondary · 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.

Group	Value	95% CI
Open Shunt Group	-0.3	± 6.61
Closed Shunt Group	-0.1	± 4.02

Change in Gait Velocity From Shunt Activation to 8 Months After Active Shunting Secondary · 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).

Group	Value	95% CI
All Randomized Patients	0.38	± 0.229

Change in Cognition Using MoCA From Baseline to 8 Months After Active Shunting Secondary · 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.

Group	Value	95% CI
All Randomized Patients	1.0	± 2.92

Change in Bladder Control From Baseline to 8 Months After Active Shunting Secondary · 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.

Group	Value	95% CI
All Randomized Patients	-25.0	± 29.42

Change in Function Using ADL/IADL From Baseline to 8 Months After Active Shunting Secondary · 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.

Group	Value	95% CI
All Randomized Patients	-4.7	± 5.88

Change in Function Using MRS From Baseline to 8 Months After Active Shunting Secondary · 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.

Group	Value	95% CI
All Randomized Patients	-0.6	± 0.96

Change in Cognition Using SDMT From Baseline to 8 Months After Active Shunting Secondary · 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.

Group	Value	95% CI
All Randomized Patients	5.8	± 7.21

Adverse events — posted to ClinicalTrials.gov

Time frame: From time of randomization until 1 year after initial shunting procedure.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Open Shunt Group

Serious: 3/9 (33%)

Deaths: 1/9

Closed Shunt Group

Serious: 1/9 (11%)

Deaths: 1/9

Serious adverse events (6 terms)

Reaction	System	Open Shunt Group	Closed Shunt Group
Muscular Weakness	Musculoskeletal and connective tissue disorders	—	—
Cerebrovascular Accident	Nervous system disorders	—	—
Urosepsis	Infections and infestations	—	—
Subdural Effusion	Nervous system disorders	—	—
Coagulopathy	Blood and lymphatic system disorders	—	—
Gallbladder necrosis	Hepatobiliary disorders	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Open Shunt Group	Closed Shunt Group
Transient Decrease in MOCA Score	Investigations	—	—
Headache	Nervous system disorders	—	—
Abdominal tenderness	Gastrointestinal disorders	—	—
Head injury	Injury, poisoning and procedural complications	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—
Balance disorder	Nervous system disorders	—	—
Crohn's disease	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—

Most-reported serious reactions: Muscular Weakness, Cerebrovascular Accident, Urosepsis, Subdural Effusion, Coagulopathy, Gallbladder necrosis.

Data from ClinicalTrials.gov NCT03350750 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Placebo-Controlled Effectiveness of Idiopathic Normal Pressure Hydrocephalus Shunting: A Randomized Pilot Trial.
   Luciano M, Holubkov R, Williams MA, Malm J, et al · · 2023 · cited 18× · PMID 36700738 · DOI 10.1227/neu.0000000000002225
2. The Current State of Clinical Trials Studying Hydrocephalus: An Analysis of ClinicalTrials.gov.
   Abraham ME, Povolotskiy R, Gold J, Ward M, et al · · 2020 · cited 3× · PMID 32983722 · DOI 10.7759/cureus.10029