Non-invasive Diagnostics of Shunt Obstruction in Adult Hydrocephalus

Official title

Randomized Controlled Study on Non-invasive Diagnostics of Shunt Obstruction in Adult Hydrocephalus

Overview

The goal of this RCT is to test whether volumetric assessment of magnetic resonance imaging (MRI) could diagnose shunt obstruction in Adult Hydrocephalus patients, and in addition to explore correlations of blood biomarkers surrounding shunt obstruction. Thirdly to investigate correlations with clinical symptom burden before and after surgery. The main questions it aims to answer are: Can volumetric assessment of cerebrospinal fluid (CSF) aid in diagnosis of shunt obstruction? Are there dynamical changes in blood biomarker concentrations after shunt obstruction? How are clinical symptom burden and dynamics correlated with blood biomarker changes and volumetric changes in CSF? After three months of shunt treatment, researchers will compare patients with "Virtual OFF" setting, to explore if simulated shunt obstruction affect measures mentioned above. Participants randomized to the intervention group will undergo the 'Virtual OFF' setting for a period of 5-7 days, starting 3 months after initiation of shunt treatment. Symptom burden will be assessed preoperatively, at follow-up, and following the week of the shunt setting change. MRI scans will be conducted at these same time points. Participants in the control group will also meet with a nurse, but their shunt settings will remain unchanged. The control group will receive the same symptom assessments and MRI scans as the intervention group.

Interventions

• Device Intervention group "Virtual OFF"
  Patients randomized to shunt setting "Virtual Off" at the three month follow-up visit. After 5-7 days, the setting will be restored to the previous setting.
• Device Control group (no change in shunt setting)
  Patients randomized to continue their shunt setting unchanged

Primary outcome measures

• Volumetry of CSF [Time frame: Preoperatively --> 3 months postop --> 3 months + 5-7 days postop]

Secondary outcome measures (1)

• Symptom burden [Time frame: Preoperatively --> 3 months postop --> 3 months + 5-7 days postop]

Eligibility criteria

Inclusion criteria

• Patients with normal pressure hydrocephalus (NPH)
• Treated at either the Hydrocephalus Research Unit in Gothenburg or at the Department of Neurological Surgery at Linköping University Hospital or Sahlgrenska University Hospital

Exclusion criteria

• Unable to conform to instructions of the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Diagnostic

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Liden S, Farahmand D, Laurell K. Ventricular volume in relation to lumbar CSF levels of amyloid-beta 1-42, tau and phosphorylated tau in iNPH, is there a dilution effect? Fluids Barriers CNS. 2022 Jul 17;19(1):59. doi: 10.1186/s12987-022-00353-9. PMID 35843939
• Hallen T, Olsson DS, Hammarstrand C, Farahmand D, Olofsson AC, Jakobsson Ung E, Jakobsson S, Bergquist H, Blennow K, Zetterberg H, Johannsson G, Skoglund T. Circulating brain injury biomarkers increase after endoscopic surgery for pituitary tumors. J Clin Neurosci. 2021 Jul;89:113-121. doi: 10.1016/j.jocn.2021.04.030. Epub 2021 May 12. PMID 34119253
• Newcombe VFJ, Ashton NJ, Posti JP, Glocker B, Manktelow A, Chatfield DA, Winzeck S, Needham E, Correia MM, Williams GB, Simren J, Takala RSK, Katila AJ, Maanpaa HR, Tallus J, Frantzen J, Blennow K, Tenovuo O, Zetterberg H, Menon DK. Post-acute blood biomarkers and disease progression in traumatic brain injury. Brain. 2022 Jun 30;145(6):2064-2076. doi: 10.1093/brain/awac126. PMID 35377407
• Saehle T, Farahmand D, Eide PK, Tisell M, Wikkelso C. A randomized controlled dual-center trial on shunt complications in idiopathic normal-pressure hydrocephalus treated with gradually reduced or "fixed" pressure valve settings. J Neurosurg. 2014 Nov;121(5):1257-63. doi: 10.3171/2014.7.JNS14283. Epub 2014 Sep 5. PMID 25192478
• Farahmand D, Saehle T, Eide PK, Tisell M, Hellstrom P, Wikkelso C. A double-blind randomized trial on the clinical effect of different shunt valve settings in idiopathic normal pressure hydrocephalus. J Neurosurg. 2016 Feb;124(2):359-67. doi: 10.3171/2015.1.JNS141301. Epub 2015 Aug 28. PMID 26315004
• Miskin N, Patel H, Franceschi AM, Ades-Aron B, Le A, Damadian BE, Stanton C, Serulle Y, Golomb J, Gonen O, Rusinek H, George AE; Alzheimer's Disease Neuroimaging Initiative. Diagnosis of Normal-Pressure Hydrocephalus: Use of Traditional Measures in the Era of Volumetric MR Imaging. Radiology. 2017 Oct;285(1):197-205. doi: 10.1148/radiol.2017161216. Epub 2017 May 10. PMID 28498794
• Neikter J, Agerskov S, Hellstrom P, Tullberg M, Starck G, Ziegelitz D, Farahmand D. Ventricular Volume Is More Strongly Associated with Clinical Improvement Than the Evans Index after Shunting in Idiopathic Normal Pressure Hydrocephalus. AJNR Am J Neuroradiol. 2020 Jul;41(7):1187-1192. doi: 10.3174/ajnr.A6620. Epub 2020 Jun 11. PMID 32527841
• Hakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci. 1965 Jul-Aug;2(4):307-27. doi: 10.1016/0022-510x(65)90016-x. No abstract available. PMID 5889177

Identifiers

NCT: NCT07172841 · Dnr 2024-01568-01 · Dnr: SU2024-06898

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗