Function and Composition of Regulatory B Cells in Participants With Glioblastoma

NCT04128774 | Terminated

• 3 other identifiers: 2019.554CCA2018-5-50NL71359.029.19
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma, Adult

Keywords

Glioma; Glioblastoma; Adult; Dexamethasone; B cells; Regulatory B cells

Outcome Measures

Primary Outcomes (1)

• Frequency of regulatory B cells in blood of participant with Glioblastoma

  ldentify if dexamethasone treatment alters the frequency and functionality of atypic B cells (CD25+CD95Fas+-B cells) in blood in GBM.

  Two weeks

Secondary Outcomes (2)

• Changes in frequency of regulatory B cells after treatment of participants with Glioblastoma with dexamethasone

  Two weeks

• Changes in frequency of regulatory B cells in participants with Glioblastoma

  Two weeks

Study Arms (2)

GBM-dexa

Participants with clinical diagnosis of GBM, that require dexamethasone due to neurological deficits. Dose is based on the clinical judgement of the treating physician but should be given at least two weeks. Dexamethasone is given once a day.

Drug: Dexamethasone

GBM-control

Participants with clinical diagnosis of GBM not requiring dexamethasone treatment.

Interventions

Dexamethasone DRUG

The case group receives dexamethasone based on the clinical indication.

Also known as: Dexamethasone indicated based on the clinical indication.

GBM-dexa

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with clinical diagnosis Gliobastoma

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

Amsterdam Medical Universities

Amsterdam, North Holland, 1081HV, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 30701669 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Mathilde CM Kouwenhoven, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 16, 2019
• Study Start: January 1, 2021
• Primary Completion: November 20, 2024
• Study Completion: November 20, 2024
• Last Updated: November 26, 2024

Record last verified: 2024-11

Locations

NL (1)