CSF Shunt Surgery for Normal Pressure Hydrocephalus

(PENS Trial)

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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a special device that manages brain fluid flow in patients with a condition called idiopathic Normal Pressure Hydrocephalus. The device can be adjusted to manage symptoms by either allowing or blocking fluid drainage.

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 data supports the idea that CSF Shunt Surgery for Normal Pressure Hydrocephalus is an effective treatment?

The available research shows that the Codman Hakim programmable shunt valve is effective in treating hydrocephalus, including normal pressure hydrocephalus. In a study comparing this programmable valve to a conventional valve, it was found to be safe and effective. Another study highlighted its usefulness in gradually reducing ventricle size in patients with idiopathic normal pressure hydrocephalus. This suggests that the programmable valve can be adjusted to meet individual patient needs, potentially reducing complications like overdrainage or underdrainage. While the research primarily focuses on hydrocephalus in general, these findings support the effectiveness of the treatment for normal pressure hydrocephalus specifically. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment CSF Shunt Surgery for Normal Pressure Hydrocephalus?

Research shows that the Codman Hakim programmable shunt valve, used in CSF shunt surgery, allows doctors to adjust the fluid pressure in the brain, which can help reduce symptoms in patients with normal pressure hydrocephalus. This valve has been particularly useful in gradually decreasing ventricle size, which is beneficial for patients with this condition. ^{1 2 3 4 5}

What safety data exists for programmable CSF shunt valves in treating normal pressure hydrocephalus?

The safety of programmable CSF shunt valves has been evaluated in studies like the SVASONA trial, which compared programmable valves with and without gravitational units to minimize overdrainage complications. The meta-analysis on programmable shunt valves also aimed to assess their benefits and adverse effects, although it noted that these aspects have not been well assessed overall. ^{6 7 8 9 10}

Is the CSF shunt surgery for normal pressure hydrocephalus generally safe?

Programmable shunt valves, used in CSF shunt surgery, have been studied for safety. A study found that adding gravitational units to these valves can help reduce complications like overdrainage, which is when too much fluid is removed, making the procedure safer. ^{6 7 8 9 10}

Is the Programmable CSF Shunt Valve a promising treatment for Normal Pressure Hydrocephalus?

Yes, the Programmable CSF Shunt Valve is a promising treatment for Normal Pressure Hydrocephalus. It allows doctors to adjust the fluid pressure in the brain without surgery, which helps tailor the treatment to each patient's needs. This can lead to better outcomes, as it helps manage symptoms effectively and reduces complications like overdrainage or underdrainage. ^{2 3 5 11 12}

How does the programmable CSF shunt valve treatment differ from other treatments for normal pressure hydrocephalus?

The programmable CSF shunt valve is unique because it allows doctors to adjust the pressure of cerebrospinal fluid drainage non-invasively, which helps tailor the treatment to each patient's needs and reduces the risk of complications like overdrainage or underdrainage. ^{2 3 5 11 12}

Research Team

Mark Luciano

Principal Investigator

Johns Hopkins University

Richard Holubkov, PhD

Principal Investigator

University of Utah

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Programmable valve breakage in shunt systems of children with posthemorrhagic hydrocephalus after minor head trauma-a case series. [2022]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The use of the Codman-Medos Programmable Hakim valve in the management of patients with hydrocephalus: illustrative cases. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The programmable shunt-system Codman Medos Hakim: A clinical observation study and review of literature. [2019]

5. United States 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. [2006]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of programmable shunt valves for hydrocephalus: A meta-analysis. [2018]

7. Austria pubmed.ncbi.nlm.nih.gov

On the method of a randomised comparison of programmable valves with and without gravitational units: the SVASONA study. [2012]

8. France pubmed.ncbi.nlm.nih.gov

St Jude Medical Portico valve. [2012]

9. Japan pubmed.ncbi.nlm.nih.gov

Transcatheter Aortic Valve Implantation (TAVI) for Native Aortic Valve Regurgitation - A Systematic Review. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Implantation and 30-Day Follow-Up on All 4 Valve Sizes Within the Portico Transcatheter Aortic Bioprosthetic Family. [2019]

11. Austria pubmed.ncbi.nlm.nih.gov

Clinical experience with a new pressure-adjustable shunt valve. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

A nonradiographic system for assessing pressure for the Codman-Hakim Programmable Valve. [2010]