Antisecretory Factor in Primary Glioblastoma 1

NCT ID: NCT04116138

Last Updated: 2021-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-01
• Study Completion Date: 2021-03-31

Brief Summary

This is a non-randomised, open-label, single center-centre, Phase I-II study in patients with newly diagnosed glioblastoma. 5 patients with newly diagnosed glioblastoma are enrolled in the study and will receive an egg powder enriched for antisecretory factor (AF), Salovum, daily from 2 days before concomitant radio-chemo therapy until 14 days after finalisation.The primary aim of the study is to asses safety and feasibility of this regimen.

Detailed Description

Glioblastoma (GBM) is the most common primary brain tumor and also has the worst prognosis with a mean survival time below 1 year and a 5-year survival rate of less than 2%.

AF is a 41kilodalton endogenous and essential protein encompassing antisecretory and anti-inflammatory effect. Endogenous AF activity increases after exposure to bacterial toxins and endogenous triggers of inflammation. The active amino-terminal portion of AF has been synthesized as a 16 amino acid peptide (AF-16) and has been used in animal experimental studies. Salovum® is a product based on egg yolk powder B221® and contains high levels of AF. Salovum® is classified as food for special medicinal purposes (FSMP) by the European Union.

Many tumors show elevated interstitial fluid pressure (IFP) compared to the surrounding tissue due to vascular leakage, providing a barrier for drug uptake in solid tumors, as well as poor perfusion, resulting in hypoxia and relative resistance to radiochemotherapy.

In a mouse model of malignant brain tumor, preliminary findings show that intratumoral infusion of AF-16 greatly enhances the effect of simultaneous intratumoral temozolomide treatment (90% and 40% survival, respectively). AF-16 also has preliminarily significant immune modulatory effects on myeloid cells in vitro, but also effects on the secretion of immune modulatory agents from tumor cells. AF-16 was reported to significantly reduce the IFP in xenotransplanted human glioblastoma by inhibiting an ionic pump, NKCC1, in the tumor tissue. Both Salovum® and AF-inducing specific processed cereals (SPC) prolonged survival in the same models. Systemic temozolomide treatment combined with AF inducing SPC completely blocked tumor growth in GBM xenografts. Likewise, SPC treatment abrogated 90% of pre-established syngeneic tumors in immune competent animals.

Mechanistically, it remains unclear whether AF's effect in tumor models is mediated through decrease of IFP and/or immunomodulation. Also, an effect on the complement system through modulation of circulating complement complexes with proteasome units has been proposed.

Salovum® has been administered to patients with various diseases as, inflammatory bowel disease, Mb Ménière and mastitis and traumatic brain injury without signs of any adverse effects.

The described study is a safety and feasibility study and if these criteria are fulfilled, will be followed by a randomised controlled trial.

Conditions

Glioblastoma; Cerebral Edema; Chemotherapy Effect

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Salovum

Salovum®, an egg powder enriched for anti secretory factor.

Group Type: EXPERIMENTAL

Salovum

Intervention Type: DIETARY_SUPPLEMENT

Egg yolk powder enriched for anti secretory factor

Interventions

Salovum

Egg yolk powder enriched for anti secretory factor

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Antisecretory factor

Eligibility Criteria

Inclusion Criteria

1. Pathology verified glioblastoma

2. Age 18-69 years

3. Surgical treatment-biopsy or resection.

4. Scheduled full concomitant radiochemotherapy treatment with radiation (60 Gy) and temozolomide,

5. Informed consent

Exclusion Criteria

1. No informed consent

2. Egg yolk allergy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Region Skane

OTHER

Sponsor Role: collaborator

Lund University

OTHER

Sponsor Role: collaborator

Skane University Hospital

OTHER

Sponsor Role: collaborator

Lantmannen Medical AB

OTHER

Sponsor Role: collaborator

Peter Siesjö

OTHER

Sponsor Role: lead

Responsible Party

Peter Siesjö

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Peter Siesjö, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Skane University Hospital

Locations

Department of Neurosurgery

Lund, , Sweden

Countries

Sweden

References

Ehinger E, Kopecky J, Darabi A, Visse E, Edvardsson C, Tomasevic G, Cederberg D, Belting M, Bengzon J, Siesjo P. Antisecretory factor is safe to use as add-on treatment in newly diagnosed glioblastoma. BMC Neurol. 2023 Feb 18;23(1):76. doi: 10.1186/s12883-023-03119-4.

Reference Type: DERIVED

PMID: 36803465 (View on PubMed)

Other Identifiers

AFGBM1

Identifier Type: -

Identifier Source: org_study_id