CSF Shunt Surgery for Normal Pressure Hydrocephalus

(PENS Trial)

Recruiting in Palo Alto (17 mi)

+16 other locations

Overseen by Mark Luciano

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: Johns Hopkins University

No Placebo Group

Approved in 4 Jurisdictions

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.

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 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 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}

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.

Treatment Details

Interventions

• Programmable CSF Shunt Valve (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 Canada, Japan for the following indications:

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+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Jordan Gladman

National Institute of Neurological Disorders and Stroke (NINDS)

Chief Medical Officer

MD from Harvard Medical School

Walter J. Koroshetz

National Institute of Neurological Disorders and Stroke (NINDS)

Chief Executive Officer since 2007

MD from the University of Chicago

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]

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]