Function and Composition of Regulatory B Cells in Participants With Glioblastoma

NCT ID: NCT04128774

Last Updated: 2024-11-26

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 5 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2024-11-20

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Dexamethasone

Intervention Type: DRUG

The case group receives dexamethasone based on the clinical indication.

GBM-control

Participants with clinical diagnosis of GBM not requiring dexamethasone treatment.

No interventions assigned to this group

Interventions

Dexamethasone

The case group receives dexamethasone based on the clinical indication.

Intervention Type: DRUG

Other Intervention Names

Dexamethasone indicated based on the clinical indication.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

Mathilde Kouwenhoven

Neurologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mathilde CM Kouwenhoven, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location VUmc

Locations

Amsterdam Medical Universities

Amsterdam, North Holland, Netherlands

Countries

Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 30701669 (View on PubMed)

Other Identifiers

CCA2018-5-50

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NL71359.029.19

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019.554

Identifier Type: -

Identifier Source: org_study_id