Clinical trial NCT05232838: US Pilot Study of the CereVasc® eShunt® System in Normal Pressure Hydrocephalus
Official title: US Pilot Study to Evaluate the Safety and Effectiveness of the CereVasc® eShunt® System in the Treatment of Normal Pressure Hydrocephalus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hydrocephalus, Normal Pressure
Hydrocephalus
Keywords: eShunt
Minimally invasive shunt
Endovascular shunt
Lead sponsor: CereVasc Inc
Sponsor class: INDUSTRY
Collaborators: name: AlvaMed, Inc.
name: Simplified Clinical Data Systems, LLC
First posted: 2022-02-10
Enrollment: 50
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

Brief summary: The eShunt® System is a minimally invasive method of treating communicating hydrocephalus. The eShunt System includes a proprietary eShunt Delivery System and the eShunt Implant, a permanent implant deployed in a minimally invasive, neuro-interventional procedure. The eShunt System is intended to shunt cerebrospinal fluid from the intracranial subarachnoid space to the venous system for the treatment of patients with normal pressure hydrocephalus, reducing disability due to symptoms including one or more of gait disturbance, cognitive dysfunction and urinary incontinence.

Detailed description: This is a prospective, non-randomized, open-label, multi-center, pilot study in subjects with normal pressure hydrocephalus for whom a traditional cerebrospinal fluid (CSF) shunt implant is indicated.

Up to 50 subjects will receive the eShunt Implant at up to 12 investigational sites. It is anticipated that up to 250 patients may need to be enrolled (consented) in order to result in 50 subjects who qualify according to the inclusion/exclusion criteria. Subjects will return for five follow-up visits in the first year and then continue to attend visits every six months until the study is closed or up to five years post-implantation.

The study objectives are to demonstrate safety of the eShunt Procedure, as well as demonstrate safety and efficacy of the eShunt Implant in a small sample of patients. Subjects will be followed long-term; primary analysis results will be used to support additional studies.

Eligibility criteria: Inclusion Criteria:

1. Patients 65-85 years old for whom traditional CSF shunt placement is indicated based upon a diagnostic normal pressure hydrocephalus (NPH) evaluation
2. Patient or legally authorized representative is able and willing to provide written informed consent
3. History or evidence of gait impairment duration ≥6 months
4. Clinical presentation consistent with NPH including 2 or more of the clinical triad (i.e., history of gait disturbance, progressive mental deterioration, and urinary urgency or incontinence), together with:

   1. Brain MRI signs of ventricular enlargement disproportionate to cerebral atrophy (Evans' Index \>0.3) and the absence of severe hippocampal atrophy
   2. Pre-procedure spinal tap test or lumbar drain with subsequent gait disturbance improvement (Timed Up and Go Test) of at least 20%
   3. CSF opening pressure ≥8 cmH2O
   4. Baseline cognitive evaluation assessed by Montreal Cognitive Assessment (MoCA) test score ≥12
5. Pre-procedure MRI confirmation of anatomy suitable for eShunt Procedure, as described in Section 1.8.3.4.2 and confirmed by subject screening committee (SSC)
6. Pre-procedure CT confirmation of anatomy suitable for eShunt Procedure, as described in Section 1.8.3.4.2 and confirmed by SSC

Exclusion Criteria:

1. Unable to walk 10 meters (33 feet) with or without an assistive device
2. Signs or symptoms of obstructive hydrocephalus
3. Active systemic infection or infection detected in CSF
4. Prior or existing shunts, endoscopic third ventriculostomy, or any previous surgical intervention for hydrocephalus
5. Hypersensitivity or contraindication to heparin or radiographic contrast agents which cannot be adequately pre-medicated, desensitized or where no alternative is available
6. Occlusion or stenosis of the internal jugular vein
7. Venous distension in the neck on physical exam
8. Atrial septal defect or patent foramen ovale identified on cardiac echocardiogram
9. History of bleeding diatheses, coagulopathy or will refuse blood transfusion in cases of emergency
10. Stroke or transient ischemic attack within 180 days of eShunt Procedure
11. Presence of a deep vein thrombosis superior to the popliteal vein
12. International Normalized Ratio (INR) or Partial Thromboplastin Time (PTT) results outside of normal range (INR 0.8-1.4; PTT 25-35 seconds)
13. Presence of a posterior fossa tumor or mass
14. Life expectancy \< 1 year
15. Currently participating in another investigational drug or device trial that could conflict with study data collection or follow-up
16. Other medical illnesses that may cause the patient to be non-compliant with the protocol or confound data interpretation
17. Unwilling or unable to comply with follow-up requirements

Primary outcomes:
measure: Device and/or procedure-related serious adverse events (SAEs)
timeFrame: 90 days following eShunt Implant deployment
Secondary outcomes:
measure: Number of participants with abnormal MRI findings
timeFrame: 90 days following eShunt Implant deployment
measure: Number of participants with abnormal CT findings
timeFrame: 90 days following eShunt Implant deployment
measure: Number of participants with clinically significant abnormal complete blood count (CBC) results
timeFrame: 90, 180, and 365 days following eShunt Implant deployment
measure: Number of participants with clinically significant abnormal blood chemistry results
timeFrame: 90, 180, and 365 days following eShunt Implant deployment
measure: Number of participants with clinically significant abnormal neurological exam findings
timeFrame: 90, 180, and 365 days following eShunt Implant deployment and at study completion
measure: Number of participants with adverse events
timeFrame: 90, 180 and 365 days following eShunt Implant deployment and at study completion
measure: Change in gait compared to baseline
timeFrame: 90, 180 and 365 days following eShunt Implant deployment
measure: Change in cognitive ability compared to baseline
timeFrame: 90, 180 and 365 days following eShunt Implant deployment
measure: Change in urinary symptoms compared to baseline
timeFrame: 90, 180 and 365 days following eShunt Implant deployment
measure: Change in Modified Rankin Scale compared to baseline
timeFrame: 90, 180 and 365 days following eShunt Implant deployment
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Jacksonville
country: United States
facility: Baptist Health
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Research Foundation
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: University at Buffalo,
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
References:
citation: Heilman CB, Basil GW, Beneduce BM, Malek AM. Anatomical characterization of the inferior petrosal sinus and adjacent cerebellopontine angle cistern for development of an endovascular transdural cerebrospinal fluid shunt. J Neurointerv Surg. 2019 Jun;11(6):598-602. doi: 10.1136/neurintsurg-2018-014445. Epub 2019 Jan 9.
citation: Lylyk P, Lylyk I, Bleise C, Scrivano E, Lylyk PN, Beneduce B, Heilman CB, Malek AM. First-in-human endovascular treatment of hydrocephalus with a miniature biomimetic transdural shunt. J Neurointerv Surg. 2022 May;14(5):495-9. doi: 10.1136/neurintsurg-2021-018136. Epub 2021 Dec 3.
citation: Welk B, Morrow S, Madarasz W, Baverstock R, Macnab J, Sequeira K. The validity and reliability of the neurogenic bladder symptom score. J Urol. 2014 Aug;192(2):452-7. doi: 10.1016/j.juro.2014.01.027. Epub 2014 Feb 8.
citation: Welk B, Lenherr S, Elliott S, Stoffel J, Gomes CM, de Bessa J, Cintra LKL, Myers JB; Neurogenic Bladder Research Group. The creation and validation of a short form of the Neurogenic Bladder Symptom Score. Neurourol Urodyn. 2020 Apr;39(4):1162-1169. doi: 10.1002/nau.24336. Epub 2020 Mar 20.
citation: Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.