Prognostic Potential of Olfactory Function in Glioblastoma: a Prospective Observational Study (OLFGBM)

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.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma Multiforme, Adult; Glioblastoma, Adult; Glioblastoma or Gliosarcoma
• Intervention / Treatment: Diagnostic test: olfactory testing (threshold and identification test)

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.

• Study Type: Observational
• Enrollment (Estimated): 128

Contacts and Locations

• Study Contact: Name: Christoph Oster, Dr. med.; Phone Number: +49201-723-82598; Email: christoph.oster@uk-essen.de
• Study Contact Backup: Name: Sied Kebir, PD Dr. med.; Phone Number: +49201-723-83133; Email: sied.kebir@uk-essen.de

Study Locations

• Germany
  • Essen, Germany, 45147
    • Recruiting
    • University Hospital Essen, Department of Neurology, Division of Clinical Neuro-Oncology
    • Contact: Christoph Oster, Dr. med.; Phone Number: +49 201 723 82598; Email: christoph.oster@uk-essen.de
  • Münster, Germany
    • Recruiting
    • Department of Neurosurgery
    • Contact: Michael Müther, PD Dr. med.; Phone Number: +49 251 83-47472; Email: Michael.Muether@ukmuenster.de

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Newly-diagnosed glioblastoma

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Newly-diagnosed glioblastoma cohort	Diagnostic test: olfactory testing (threshold and identification test); 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.
Control cohort; Control group of patients with non-tumourous (neurological) diseases not primarily associated with an olfactory dysfunction	Diagnostic test: olfactory testing (threshold and identification test); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival in relation to olfactory function	From enrollment to 2 years after the end of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival in relation to olfactory function	From enrollment to 2 years after the end of radiotherapy
Neurocognition	Neurocognition in relation to olfactory function The following tests are used for neurocognition testing: Immediate and delayed story recall from the Rivermead Behavioural Memory Test; Number span (forward and backward) and block span (forward and backward) from the Wechsler Memory Scale; Phonemic word fluency from the Regensburg Word Fluency Test (phonemic); Trail Making Test A and B	From enrollment to 2 years after the end of radiotherapy
Quality of Life (QoL)	Quality of Life in relation to olfactory function The following questionnaires are used to assess quality of life: EORTC QLQ-C30 (Version 3.0; Part A with 28 questions on a Likert scale, 28 to 112 points, Higher score means lower quality of life; Part B with 2 questions on a Likert scale, 2 to 14 points, Lower score means lower quality of life ); EORTC QLQ-BN20 (20 questions on a Likert scale; 20 to 80 points; Higher score means lower quality of life)	From enrollment to 2 years after the end of radiotherapy
Psychological condition	Psychological well-being in relation to olfactory function The following psychiatric questionnaires are used: Patient Health Questionnaire-8 (PHQ-8):8 questions on a Likert scale, score 0 to 24, higher score indicate more depression; Generalized Anxiety Disorder 7 (GAD-7):7 questions on a Likert scale, score 0 to 21, higher score indicate more anxiety; National Comprehensive Cancer Network (NCCN) Distress Thermometer: Score 1 to 10, higher score indicate more distress	From enrollment to 2 years after the end of radiotherapy

Collaborators and Investigators

• Sponsor: Sied Kebir
• Collaborators: Münster University Hospital, Germany

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 16, 2025
• First Submitted That Met QC Criteria: April 24, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: quality of life; prognosis; olfactory function; glioblastoma; observational study; olfactory dysfunction; neurocognition; threshold test; identification test
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Gliosarcoma
• Other Study ID Numbers: 22-10501-BO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Clinical Data from the other study centers will be transferred pseudonymously to the study headquarters in Essen. Only pseudonymized data is also used for accompanying scientific projects.

Drug and device information, study documents

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