CSF Shunt Surgery for Normal Pressure Hydrocephalus

(PENS Trial)

Not currently recruiting at 16 trial locations

Overseen By Jessica Wollett

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Must not be taking: Neuroleptics, Antidepressants

Disqualifiers: Secondary NPH, Parkinsonian syndrome, Dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a programmable shunt for individuals with idiopathic Normal Pressure Hydrocephalus (iNPH), a condition that can cause walking problems, balance issues, and memory difficulties. The trial compares two groups: one with an active shunt and another with a temporarily inactive shunt. It is suitable for those diagnosed with iNPH who have experienced gait problems for at least six months. Participants should be able to walk 10 meters (about 33 feet) and be comfortable returning for follow-up evaluations. As an unphased trial, this study offers participants the chance to contribute to valuable research that could enhance treatment options for iNPH.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial investigators for guidance.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that this CSF shunt surgery is safe for iNPH patients?

Research has shown that the programmable CSF (cerebrospinal fluid) shunt valve is safe for treating idiopathic normal pressure hydrocephalus (iNPH). Studies have found that these valves lead to better neurological outcomes with fewer complications compared to fixed pressure valves. This suggests the programmable valve can help prevent issues like over-draining or under-draining fluid.

The valve used in this study has FDA approval, indicating it has been tested and found safe for specific uses. The goal is to achieve optimal fluid drainage balance, reducing the need for additional surgeries. While most people tolerate the valve well, individual experiences can vary. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the programmable CSF shunt valve for normal pressure hydrocephalus because it offers precise control over fluid drainage, which isn't available in standard fixed-pressure shunts. Unlike traditional treatments, this valve can be adjusted non-invasively, allowing clinicians to fine-tune the pressure settings based on the patient’s unique needs. This customization could potentially reduce complications and improve patient outcomes over time, making it a promising advancement in hydrocephalus treatment.

What evidence suggests that the Programmable CSF Shunt Valve is effective for normal pressure hydrocephalus?

This trial will compare two groups using programmable CSF shunt valves for treating idiopathic normal pressure hydrocephalus (iNPH). Research has shown that these adjustable brain fluid valves can effectively treat iNPH. One study found that surgery to insert these shunts significantly improved walking speed in people with iNPH. Another study showed that these shunts are safe and can reduce the need for additional surgeries to address issues. The adjustable feature allows doctors to control fluid drainage, helping to prevent complications. Overall, evidence supports that programmable CSF shunts are helpful for managing iNPH symptoms. ^{2 3 6 7 8}

Who Is on the Research Team?

Mark Luciano

Principal Investigator

Johns Hopkins University

Richard Holubkov, PhD

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for people aged 60 or older with idiopathic Normal Pressure Hydrocephalus (iNPH) who have been recommended for shunt surgery. They must be able to walk at least 10 meters, give consent, and follow the study's procedures. Exclusions include recent strokes, Parkinsonian syndrome, severe dementia, prior brain surgeries for hydrocephalus, unrelated gait impairing conditions, certain psychiatric diagnoses affecting outcome evaluation, and contraindications to MRI.

Inclusion Criteria

I have had a positive result from a major spinal fluid test.

I have had trouble walking properly for at least 6 months.

I have been diagnosed with iNPH and recommended for shunt surgery.

Exclusion Criteria

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)

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

My Parkinson's symptoms may affect the trial's results, as judged by a doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either an active or placebo shunt for three months, followed by adjustment to active shunt for all participants

3 months

Regular visits for shunt adjustment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 9 and 12 months

9 months

Assessments at 9 and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Programmable CSF Shunt Valve

Trial Overview

The PENS trial is testing the effectiveness of a programmable cerebrospinal fluid (CSF) shunt valve in patients with iNPH. Participants are randomly assigned to receive either the actual shunt surgery or a placebo procedure in this blinded study across multiple centers.

How Is the Trial Designed?

Group I: Open Shunt Group Active Control 1 Intervention

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

Group II: Closed Shunt Group Placebo Group 1 Intervention

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) three months after the procedure.

Programmable CSF Shunt Valve is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Programmable CSF Shunt Valve for:

• Idiopathic Normal Pressure Hydrocephalus (iNPH)
• Hydrocephalus
• Pediatric hydrocephalus

Approved in United States as Programmable CSF Shunt Valve for:

• Idiopathic Normal Pressure Hydrocephalus (iNPH)
• Hydrocephalus
• Pediatric hydrocephalus

Approved in Canada as Programmable CSF Shunt Valve for:

• Idiopathic Normal Pressure Hydrocephalus (iNPH)
• Hydrocephalus
• Pediatric hydrocephalus

Approved in Japan as Programmable CSF Shunt Valve for:

• Idiopathic Normal Pressure Hydrocephalus (iNPH)
• Hydrocephalus
• Pediatric hydrocephalus

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

The St Jude Medical Portico transcatheter valve system is specifically designed to address challenges faced during transcatheter aortic valve implantation (TAVI) procedures for high-risk patients with symptomatic aortic valve disease.

Clinical experiences with the Portico valve system suggest it may improve procedural outcomes, although specific data on efficacy and safety were not detailed in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

St Jude Medical Portico valve. Manoharan, G., Spence, MS., Rodés-Cabau, J., et al.[2012]

In a study of five children with posthemorrhagic hydrocephalus, a rare complication of programmable valve breakage occurred in 4.3% of cases involving the Codman Hakim-Medos valve, highlighting the need for awareness of this issue following minor head trauma.

All five children experienced symptoms of shunt malfunction, which were resolved after surgical replacement of the broken valve, indicating that while valve breakage is rare, it can lead to significant clinical issues that require prompt intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmable valve breakage in shunt systems of children with posthemorrhagic hydrocephalus after minor head trauma-a case series. Schwarm, FP., Nagl, J., Bender, M., et al.[2022]

In a study of 377 patients with hydrocephalus, the Codman Hakim programmable shunt valve showed comparable safety and efficacy to conventional valve systems, with similar rates of valve explantation and shunt failure over a 104-week follow-up period.

Both types of valves had similar success in controlling hydrocephalus symptoms, but the study did not have enough power to definitively compare the effectiveness of programmable versus conventional valves for specific hydrocephalus issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled study of a programmable shunt valve versus a conventional valve for patients with hydrocephalus. Hakim-Medos Investigator Group. Pollack, IF., Albright, AL., Adelson, PD.[2022]

The Codman-Medos Programmable Hakim valve system allows for non-invasive adjustments of cerebrospinal fluid (CSF) pressure, which can help optimize treatment for hydrocephalus by preventing issues like overdrainage and underdrainage.

In a pilot study involving 13 patients, this programmable valve effectively managed ventricle size in cases of idiopathic normal pressure hydrocephalus and other conditions, demonstrating its potential for tailored treatment in hydrocephalus management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of the Codman-Medos Programmable Hakim valve in the management of patients with hydrocephalus: illustrative cases. Black, PM., Hakim, R., Bailey, NO.[2019]

The Codman Medos pressure-adjustable valve system was used in a study of 90 patients (15 children and 75 adults) with various types of hydrocephalus, showing that the ability to adjust valve pressure postoperatively led to satisfactory clinical outcomes, with 64 patients experiencing excellent results.

The system effectively managed complications like underdrainage in some cases, demonstrating its utility in tailoring treatment to individual patient needs, particularly in children and adults with normal pressure hydrocephalus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with a new pressure-adjustable shunt valve. Reinprecht, A., Czech, T., Dietrich, W.[2019]

In a study involving 220 high-risk patients with severe aortic stenosis, the Portico transcatheter aortic valve replacement system demonstrated a low 30-day all-cause mortality rate of 3.6%, indicating its safety for short-term use.

The study showed that 75.8% of patients experienced an improvement in their functional class after 30 days, with no severe paravalvular leaks reported, highlighting the efficacy of the valve across all sizes used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implantation and 30-Day Follow-Up on All 4 Valve Sizes Within the Portico Transcatheter Aortic Bioprosthetic Family. Möllmann, H., Linke, A., Holzhey, DM., et al.[2019]

In a meta-analysis of 11 studies involving 2622 subjects, programmable shunt valves (PV) did not significantly improve the one-year shunt survival rate compared to non-programmable valves, indicating similar long-term effectiveness.

However, PV treatment was associated with a significantly lower revision rate and reduced complications related to over- or under-drainage, suggesting it may be a safer option, particularly for patients under 18 years old.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of programmable shunt valves for hydrocephalus: A meta-analysis. Li, M., Wang, H., Ouyang, Y., et al.[2018]

In a seven-year study of 122 children with hydrocephalus, the use of the adult Codman Hakim programmable valve allowed for non-invasive adjustments to optimize intraventricular pressure, significantly reducing the need for urgent surgical interventions due to over-drainage.

Despite being more expensive upfront, the programmable valve ultimately resulted in lower overall costs compared to non-programmable valves by decreasing the number of re-operations, leading to shorter hospital stays and improved quality of life for the children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The programmable adult Codman Hakim valve is useful even in very small children with hydrocephalus. A 7-year retrospective study with special focus on cost/benefit analysis. Arnell, K., Eriksson, E., Olsen, L.[2006]

The new Valve Programming and Verification System for the Codman-Hakim programmable valve successfully established valve settings in 62% of subjects without the need for radiographic exposure.

This system is cost-effective and time-efficient, although about one third of subjects still require cranial radiographs for verification when the adjustment is not completed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A nonradiographic system for assessing pressure for the Codman-Hakim Programmable Valve. Bailey, NO., Luciano, M., Ward, MV., et al.[2010]

The SVASONA study aims to determine if programmable valves with gravitational units can reduce the rate of overdrainage complications in patients with idiopathic normal pressure hydrocephalus (iNPH) from 25% to 10%, based on a multicenter trial involving 250 patients.

This study is designed to confirm the efficacy of these gravitational units while maintaining the favorable outcomes seen in the Dutch NPH study, with follow-ups at 3, 6, and 12 months to assess both overdrainage rates and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On the method of a randomised comparison of programmable valves with and without gravitational units: the SVASONA study. Lemcke, J., Meier, U., Müller, C., et al.[2012]

Transcatheter aortic valve implantation (TAVI) shows an 86.3% device success rate in high-risk patients with native aortic valve regurgitation, indicating it is an effective treatment option.

The use of second-generation valves resulted in higher device success rates (96.2%) compared to first-generation valves (78.4%), with similar safety profiles, suggesting advancements in valve technology may improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Aortic Valve Implantation (TAVI) for Native Aortic Valve Regurgitation - A Systematic Review. Yousef, A., MacDonald, Z., Simard, T., et al.[2019]

In a study of 101 patients with hydrocephalus treated with the Codman Medos Hakim valve, an initial pressure setting of 120 mmH2O was found to be effective for most patients, with 70.3% of valves optimized to this level.

Clinical improvement was specifically noted in patients with subarachnoid hemorrhage (SAH), where better outcomes correlated with reduced ventricular size, highlighting the importance of monitoring cranial imaging to adjust valve settings appropriately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The programmable shunt-system Codman Medos Hakim: A clinical observation study and review of literature. Nowak, S., Mehdorn, HM., Stark, A.[2019]

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This study is to compare the overall revision rate, revision cause, and revision-free survival between PV and non-programmable valve (NPV) in adult patients

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Long-term follow-up and comparison of programmable and ...

This study is to compare the overall revision rate, revision cause, and revision-free survival between PV and non-programmable valve (NPV) in adult patients