Clinical Outcome in Patients With INPH

Phenotypes, Biomarkers and Pathophysiology in INPH

The aim of this study is to determine the clinical spectrum and natural progression of idiopathic normal pressure hydrocephalus （iNPH ) and related disorders in a prospective single center study, identify digital, imaging and molecular biomarkers that can assist in diagnosis and therapy development and study the etiology and molecular mechanisms of these diseases.

Study Overview

• Status: Recruiting
• Conditions: Hydrocephalus; Idiopathic Normal Pressure Hydrocephalus; CSF; Glympathic System; Omic
• Intervention / Treatment: Diagnostic test: hydrocephalus group; Other: normal group

Detailed Description

Due to the heterogeneity of the etiology of idiopathic normal pressure hydrocephalus , almost all published studies on the clinical outcome and prognostic factors of iNPH are relatively limited, and most of them are retrospective. It is not clear which is the most reliable predictor of clinical outcome. Therefore, the researchers conducted this prospective cohort study to identify the occurrence, development and outcome of iNPH and determine the main prognostic factors through clinical scales, biomarkers and imaging.

At study visits a standardized clinical examination will be performed including application of clinical rating scales. At all study visits, patients will be asked to donate biosamples; biomaterial collection is optional and participants can elect to participate in sampling of blood, urine, CSF, and/or a muscle biopsy.

Optionally, additional examinations may be performed including imaging，such as DTIALPS, neurophysiological examination, analysis of patient or observer reported outcomes and analysis to characterize molecular biomarkers.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: fengzeng jian, md; Phone Number: 01083198899; Email: jianfengzeng@xwh.ccmu.edu.cn
• Study Contact Backup: Name: xin qu, md; Phone Number: 01083198899; Email: xinqu@xwhosp.org

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Fengzeng Jian
      • Contact: Yuan Chenghua; Email: yuanchenghua@ccmu.edu.cn
      • Contact: Jian Fengzeng; Email: jianfengzeng@xwh.ccmu.edu.cn
      • Sub-Investigator: xin qu, dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

patients who was diagnosed as idiopathic normal pressure hydrocephalus

Description

Inclusion Criteria:

• patients who was diagnosed as idiopathic normal pressure hydrocephalus

Exclusion Criteria:

• patient received surgical treatment or interventional treatment before patient is pregnant patient unable to complete follow-up patient with other types of hydrocephalus other nervous system diseases

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
hydrocephalus; high throughput sequencing and electromyography Whole Genome Sequencing, Whole Exome Sequencing, Transcriptomics, Proteomics, Metabolomics and imaging, such as DTIALPS	Diagnostic test: hydrocephalus group; Diagnostic Test: high throughput sequencing and electromyography Whole Genome Sequencing, Whole Exome Sequencing, Transcriptomics, Proteomics, Metabolomics and imaging, such as DTIALPS
Normal group; Whole Genome Sequencing, Whole Exome Sequencing, Transcriptomics, Proteomics, Metabolomics	Other: normal group; Whole Genome Sequencing, Whole Exome Sequencing, Transcriptomics, Proteomics, Metabolomics and imaging, such as DTIALPS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DTIALPS	Change of DTIALPS singal intensity in the resting state fMRI in iNPH patients compared with normal healthy group. Also, the responsive and non-responsive iNPH patients functional MRI were analzed.	Change from Baseline at 6 months after VP shunt

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kiefer score	A score for iNPH severity; range 0-26; higher indicates higher severity.	Change from Baseline at 6 months after VP shunt
Mini mental state Examination	A score for cognitive ability; range 0-30; higher indicates higher severity.	Change from Baseline at 6 months after VP shunt
Gait evaluation	10 meters walking test were evaluated of iNPH patients.	Change from Baseline at 6 months after VP shunt
modified Rankin scale	A score for functional neurological status ; range 0-5; higher indicates higher severity.	Change from Baseline at 6 months after VP shunt
Change in the resting state fMRI	Change of BOLD singal intensity in the resting state fMRI in iNPH patients compared with normal healthy group. Also, the responsive and non-responsive iNPH patients functional MRI were analzed.	Change from Baseline at 6 months after VP shunt
omic pattern of CSF in iNPH patients	Comparing the omic pattern differences in CSF between iNPH patients and normal age-matched normal volunteers by the analysis of mass spectrometry. Also, the responsive and non-responsive iNPH patients omic pattern were analzed.	Before surgery in lumbar CSF
omic pattern of CSF in iNPH patients	Comparing the omic pattern differences in CSF of iNPH patients before surgery and after VP shunt by the analysis of mass spectrometry. Also, the responsive and non-responsive iNPH patients omic pattern were analzed.	Change from Baseline at 6 months after VP shunt

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing

Publications and helpful links

General Publications

• Zhang C, Xu K, Zhang H, Sha J, Yang H, Zhao H, Chen N, Li K. Recovery of glymphatic system function in patients with temporal lobe epilepsy after surgery. Eur Radiol. 2023 Sep;33(9):6116-6123. doi: 10.1007/s00330-023-09588-y. Epub 2023 Apr 3.
• Georgiopoulos C, Tisell A, Holmgren RT, Eleftheriou A, Rydja J, Lundin F, Tobieson L. Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging. J Neurosurg. 2023 Sep 8;140(3):612-620. doi: 10.3171/2023.6.JNS23260. Print 2024 Mar 1.
• Yuan C, Xia P, Duan W, Wang J, Guan J, Du Y, Zhang C, Liu Z, Wang K, Wang Z, Wang X, Wu H, Chen Z, Jian F. Long-Term Impairment of the Blood-Spinal Cord Barrier in Patients With Post-Traumatic Syringomyelia and its Effect on Prognosis. Spine (Phila Pa 1976). 2024 Mar 15;49(6):E62-E71. doi: 10.1097/BRS.0000000000004884. Epub 2023 Nov 28.

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2024
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: May 20, 2024
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 24, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Hydrocephalus; Idiopathic Normal Pressure Hydrocephalus
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: XWCOPINPH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No