Pilot Study of the CereVasc® eShunt® System in Normal Pressure Hydrocephalus

Pilot Study to Evaluate the Safety and Effectiveness of the CereVasc® eShunt® System in the Treatment of Normal Pressure Hydrocephalus

The eShunt System includes proprietary delivery componentry and the eShunt Implant, a permanent implant deployed in a minimally invasive, neurointerventional procedure. The eShunt Implant is designed to mimic the function of the arachnoid granulations by draining excess cerebrospinal fluid (CSF) from the intracranial subarachnoid space (SAS) into the venous system.

Study Overview

• Status: Recruiting
• Conditions: Hydrocephalus; Hydrocephalus, Normal Pressure
• Intervention / Treatment: Device: eShunt Implant

Detailed Description

This is a prospective, non-randomized, open-label, single-center, pilot study in subjects with normal pressure hydrocephalus for whom a traditional CSF shunt implant is indicated.

Up to 30 subjects will receive the eShunt Implant at one investigational site. Subjects will return for five follow-up visits in the first year and then continue to attend visits every six months for 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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: DJ Cass; Email: djcass@cerevasc.com
• Study Contact Backup: Name: Ona Whelove; Phone Number: 4155152885; Email: clinicaltrials@cerevasc.com

Study Locations

• Argentina
  • Ciudad A. De Buenos Aires
    • Buenos Aires, Ciudad A. De Buenos Aires, Argentina, C1426B
      • Recruiting
      • Clínica La Sagrada Familia
      • Contact: Carlos Toranzo; Email: ctoranzo@lylyk.com.ar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients 65-85 years old and traditional CSF shunt placement is indicated based upon a diagnostic NPH evaluation
2. Patient 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 with subsequent gait disturbance improvement (Timed Up and Go Test) of at least 20%
   3. CSF opening pressure ≥10 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 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. Conditions impairing gait that are considered to be unrelated to hydrocephalus
3. Signs or symptoms of obstructive hydrocephalus
4. Active systemic infection or infection detected in CSF
5. Prior or existing shunts, endoscopic third ventriculostomy, or any previous surgical intervention for hydrocephalus
6. Hypersensitivity or contraindication to heparin or radiographic contrast agents which cannot be adequately pre-medicated, desensitized or where no alternative is available
7. Occlusion or stenosis of the internal jugular vein
8. Venous distension in the neck on physical exam
9. Atrial septal defect or patent foramen ovale identified on cardiac echocardiogram
10. History of bleeding diatheses, coagulopathy or will refuse blood transfusion in cases of emergency
11. Stroke or transient ischemic attack within 180 days of eShunt Procedure
12. Presence of a deep vein thrombosis superior to the popliteal vein
13. International Normalized Ratio (INR) or Partial Thromboplastin Time (PTT) results outside of normal range (INR 0.8-1.4; PTT 25-35 seconds)
14. Presence of a posterior fossa tumor or mass
15. Life expectancy < 1 year
16. Currently participating in another investigational drug or device trial that could conflict with study data collection or follow-up
17. Other medical illnesses that may cause the patient to be non-compliant with the protocol or confound data interpretation
18. Pregnant or planning to become pregnant
19. Unwilling or unable to comply with follow-up requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; The Treatment Arm receives the eShunt Implant.	Device: eShunt Implant; The eShunt System consists of endovascular delivery componentry and a permanent implant intended to shunt cerebrospinal fluid from the intracranial subarachnoid space to the venous system in adults.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device and/or procedure-related serious adverse events (SAEs)	Rate of occurrence of device and/or procedure-related serious adverse events (SAEs)	90 days following eShunt Implant deployment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with abnormal MRI findings	Number of participants with abnormal MRI findings and descriptive summaries of findings	90 days following eShunt Implant deployment
Number of participants with abnormal CT findings	Number of participants with abnormal CT findings and descriptive summaries of findings	90 days following eShunt Implant deployment
Number of participants with clinically significant abnormal complete blood count (CBC) results	Number of participants with clinically significant abnormal results and descriptive summaries of CBC results	90, 180 and 365 days following eShunt Implant deployment
Number of participants with clinically significant abnormal blood chemistry results	Number of participants with clinically significant abnormal findings and descriptive summaries of blood chemistry results	90, 180 and 365 days following eShunt Implant deployment
Number of participants with clinically significant abnormal neurological exam findings	Number of participants with clinically significant abnormal findings and descriptive summaries of neurological exam finding	90, 180 and 365 days following eShunt Implant deployment and at study completion
Number of participants with adverse events	Tabulation of all adverse events	90, 180 and 365 days following eShunt Implant deployment and at study completion
Change in gait compared to baseline	Change in gait compared to baseline as measured by the duration in seconds of the Timed Up and Go Test (shorter durations indicate improvement (increased mobility))	90, 180 and 365 days following eShunt Implant deployment
Change in cognitive ability compared to baseline	Change in cognitive ability compared to baseline as measured by Montreal Cognitive Assessment (MoCA) scores (scores range from 0-30; higher scores indicate improvement (less cognitive disability))	90, 180 and 365 days following eShunt Implant deployment
Change in urinary symptoms compared to baseline	Change in urinary symptoms compared to baseline as measured by the Neurogenic Bladder Symptom Score (NBSS) (scores range from 0-28; lower scores indicate improvement (fewer symptoms))	90, 180 and 365 days following eShunt Implant deployment
Change in Modified Rankin Scale compared to baseline	Change in degree of disability compared to baseline as measured by Modified Rankin Scale (mRS) scores (scores range from 0-6; lower scores indicate improvement (less disability))	90, 180 and 365 days following eShunt Implant deployment

Collaborators and Investigators

• Sponsor: CereVasc Inc
• Collaborators: AlvaMed, Inc.; Simplified Clinical Data Systems, LLC; Bioscience Consulting, Inc.
• Investigators: Principal Investigator: Pedro Lylyk, MD, Clínica La Sagrada Familia

Publications and helpful links

General Publications

• 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. Erratum In: J Am Geriatr Soc. 2019 Sep;67(9):1991.
• 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.
• 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.
• 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.
• 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.
• Serrano CM, Sorbara M, Minond A, Finlay JB, Arizaga RL, Iturry M, Martinez P, Heinemann G, Gagliardi C, Serra A, Magliano FC, Yacovino D, Rojas MMEY, Ruiz AS, Graviotto HG. Validation of the Argentine version of the Montreal Cognitive Assessment Test (MOCA): A screening tool for Mild Cognitive Impairment and Mild Dementia in Elderly. Dement Neuropsychol. 2020 Apr-Jun;14(2):145-152. doi: 10.1590/1980-57642020dn14-020007.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: February 11, 2022
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: eShunt; Minimally invasive shunt; Endovascular shunt
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: CLIN-0012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes