Clinical trial NCT06954636: Prognostic Potential of Olfactory Function in Glioblastoma: a Prospective Observational Study
Official title: Prognostic Potential of Olfactory Function in Glioblastoma: a Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Glioblastoma Multiforme, Adult
Glioblastoma or Gliosarcoma
Glioblastoma, Adult
Keywords: olfactory dysfunction
threshold test
identification test
glioblastoma
prognosis
observational study
olfactory function
neurocognition
quality of life
Lead sponsor: University Hospital, Essen
Sponsor class: OTHER
Collaborators: name: Münster University Hospital, Germany
First posted: 2025-05-01
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newly-diagnosed glioblastoma

Brief summary: The study aims to investigate the prognostic significance of olfactory function in patients with glioblastoma. We are examining olfactory function at various points during therapy and correlating the results with survival data. In addition, neurocognitive tests will be carried out to correlate the results of olfactory function with the patient's cognitive abilities. Investigations into the quality of life and psychological condition of the patients are also performed. In addition to the cohort of glioblastoma patients, there is a control cohort without tumor disease in which the olfactory testing is also carried out in order to have a comparison.

Detailed description: Background: Olfactory impairment is frequent in glioblastoma and is associated with poor overall survival. However, earlier studies were limited by confounding of important predictive factors and the lack of long-term olfactory assessments to evaluate treatment-related neurotoxicity.

Aim: To determine whether olfactory function is an independent prognostic marker for survival, quality of life and neurocognitive outcome in glioblastoma.

Design: Prospective, multicenter cohort study with 64 glioblastoma patients and 64 comparable controls without tumor disease. Patients were stratified by baseline olfactory status, extent of resection, radiologic involvement of olfactory regions,O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, age, and Karnofsky performance status.

Methods: Olfactory function will be serially assessed from diagnosis to treatment using Sniffin' Sticks (identification and threshold tests). Psychosocial assessments, neurocognitive testing and quality of life assessments will be performed at intervals. Coronal T2- and T1-weighted MRI scans will be evaluated independently by blinded neuroradiologists to identify olfactory involvement.

Next-generation sequencing will be used to investigate molecular correlates of hyposmia. As part of a parallel translational study, blood samples will be taken to analyze extracellular vesicles.

Olfactory testing:

In the identification test, 12 sniffin sticks are presented, which the patient has to name using a selection card with four terms each. Both nostrils are tested individually at each visit during the identification test. A correct answer scores one point. A maximum of 12 points is possible.

The threshold test consists of 16 dilution levels. Each level contains one sniffin stick with odor and two blanks. All three sniffin sticks of a dilution level are presented to the patient one after the other with eyes closed. The patient must indicate which of the three sticks contains an odor. Depending on whether the patient gives the correct answer, the three sniffin sticks in the next higher or next lower level are presented next. A maximum of 16 points is possible.

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age
* Newly-diagnosed glioblastoma (IDH wild-type)
* Never received prior chemotherapy
* Never received radiotherapy to the head or neck before
* KPS ≥ 70
* No history of severe head or brain trauma requiring ICU admission or classified as Glasgow Coma Scale grade 3
* No respiratory infection at the time of inclusion
* No significant aphasia

Exclusion Criteria:

* Presence of Neurodegenerative diseases (e.g. Parkinson's disease, Alzheimer's disease, Huntington's disease, Korsakoff's syndrome, Pick's disease, Shy-Drager syndrome)
* History of invasive tumors or surgery in the head or neck area, except for surgeries for non-invasive skin tumors (e.g. basal cell carcinomas)
* Permanent olfactory impairment following infections (e.g., influenza, coronavirus)
* Conditions that, in the examiner's judgment, could interfere with the participant's study compliance (e.g., schizophrenia)
* Language barriers likely to interfere with participation or comprehension of study procedures.

Primary outcomes:
measure: Overall survival
timeFrame: From enrollment to 2 years after the end of radiotherapy
Secondary outcomes:
measure: Progression free survival
timeFrame: From enrollment to 2 years after the end of radiotherapy
measure: Neurocognition
timeFrame: From enrollment to 2 years after the end of radiotherapy
measure: Quality of Life (QoL)
timeFrame: From enrollment to 2 years after the end of radiotherapy
measure: Psychological condition
timeFrame: From enrollment to 2 years after the end of radiotherapy
Other outcomes:
Locations:
city: Essen
country: Germany
facility: University Hospital Essen, Department of Neurology, Division of Clinical Neuro-Oncology
Study officials:
References:
citation: Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. 'Sniffin' sticks': olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses. 1997 Feb;22(1):39-52. doi: 10.1093/chemse/22.1.39.
citation: Hummel T, Konnerth CG, Rosenheim K, Kobal G. Screening of olfactory function with a four-minute odor identification test: reliability, normative data, and investigations in patients with olfactory loss. Ann Otol Rhinol Laryngol. 2001 Oct;110(10):976-81. doi: 10.1177/000348940111001015.
citation: Kebir S, Hattingen E, Niessen M, Rauschenbach L, Fimmers R, Hummel T, Schafer N, Lazaridis L, Kleinschnitz C, Herrlinger U, Scheffler B, Glas M. Olfactory function as an independent prognostic factor in glioblastoma. Neurology. 2020 Feb 4;94(5):e529-e537. doi: 10.1212/WNL.0000000000008744. Epub 2019 Dec 12.
citation: Walker IM, Fullard ME, Morley JF, Duda JE. Olfaction as an early marker of Parkinson's disease and Alzheimer's disease. Handb Clin Neurol. 2021;182:317-329. doi: 10.1016/B978-0-12-819973-2.00030-7.