Clinical trial NCT05250505: Pilot Study of the CereVasc® EShunt® System in Normal Pressure Hydrocephalus
Official title: 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: 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
name: Bioscience Consulting, Inc.
First posted: 2022-02-22
Enrollment: 30
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 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.

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.

Eligibility criteria: 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

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: Buenos Aires
country: Argentina
facility: Clínica La Sagrada Familia
state: Ciudad A. de Buenos Aires
Study officials:
affiliation: Clínica La Sagrada Familia
name: Pedro Lylyk, MD
role: PRINCIPAL_INVESTIGATOR
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.
citation: 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.