Clinical trial NCT04128774: Function and Composition of Regulatory B Cells in Participants With Glioblastoma
Official title: The Function and Composition of B Cells in Participants With Glioblastoma Treated With and Without Dexamethasone
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Glioblastoma, Adult
Keywords: Glioma
Glioblastoma
Adult
Dexamethasone
B cells
Regulatory B cells
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2019-10-16
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with clinical diagnosis Gliobastoma

Brief summary: Rationale: This project elaborates on a novel finding of the investigators that has not yet been reported in literature, namely the presence of elevated levels of atypical B cells in participants with glioblastoma. ln the period 2015 2018 the investigators analysed the blood immune subset composition of a cohort of 180 participants undergoing neurosurgery. The most relevant finding was the presence of an abnormally elevated level of B cells in the blood of the great majority of participants with glioblastoma. These B cells may be involved in the immunosuppression associated with glioblastoma that makes this tumor refractory to immunotherapy. Multiple regression analysis indicated that the increase in the frequency of atypical B cells in participants' peripheral blood was related with the administration of dexamethasone prior to surgery. However, this study design did not allow the investigators to address the causality of the relationship between dexamethasone and atypic B cell dysregulation. Alternative treatments to dexamethasone exist.

Objective: To investigate the effect of dexamethasone in the dysregulation of atypic B cells in participants with glioblastoma.

Study design: Observational case control pilot study with 20 participants (10 per group).

Study population: Newly diagnosed participants with glioblastoma. Intervention (if applicable): Observational study. Main study parameters/endpoints: Changes in the immune subset composition and functionality in the peripheral blood of participants with glioblastoma upon administration of dexamethasone for neurological signs of peritumoral edema (oral dexamethasone).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The investigators will collect blood (28 ml) during the first visit and again (28 ml) at the time of surgery (2 weeks ± 3 days). There will not be additional site visits, physical examinations or any other tests, questionnaires. Blood collection is only a minor discomfort and it does not represent any additional risk.


Eligibility criteria: Inclusion Criteria:

Clinical diagnosis Glioblastoma Patients are 18 years or older at first diagnosis

Exclusion Criteria:

No indication for surgery to confirm radiological diagnosis Not able or willing to give informed consent Allergy or intolerance to dexamethasone

Primary outcomes:
measure: Frequency of regulatory B cells in blood of participant with Glioblastoma
timeFrame: Two weeks
Secondary outcomes:
measure: Changes in frequency of regulatory B cells after treatment of participants with Glioblastoma with dexamethasone
timeFrame: Two weeks
measure: Changes in frequency of regulatory B cells in participants with Glioblastoma
timeFrame: Two weeks
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam Medical Universities
state: Noord-Holland
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Mathilde CM Kouwenhoven, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dusoswa SA, Verhoeff J, Garcia-Vallejo JJ. OMIP-054: Broad Immune Phenotyping of Innate and Adaptive Leukocytes in the Brain, Spleen, and Bone Marrow of an Orthotopic Murine Glioblastoma Model by Mass Cytometry. Cytometry A. 2019 Apr;95(4):422-426. doi: 10.1002/cyto.a.23725. Epub 2019 Jan 31.