Antisecretory Factor in Primary Glioblastoma 1
מילות מפתח
תַקצִיר
תיאור
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.
תאריכים
אומת לאחרונה: | 12/31/2019 |
הוגש לראשונה: | 09/25/2019 |
ההרשמה המשוערת הוגשה: | 10/01/2019 |
פורסם לראשונה: | 10/03/2019 |
העדכון האחרון הוגש: | 01/08/2020 |
עדכון אחרון פורסם: | 01/12/2020 |
תאריך תחילת לימוד בפועל: | 10/03/2019 |
תאריך סיום משוער משוער: | 03/30/2020 |
תאריך סיום משוער ללימודים: | 07/30/2020 |
מצב או מחלה
התערבות / טיפול
Dietary Supplement: Salovum
שלב
קבוצות זרועות
זְרוֹעַ | התערבות / טיפול |
---|---|
Experimental: Salovum Salovum®, an egg powder enriched for anti secretory factor. | Dietary Supplement: Salovum Egg yolk powder enriched for anti secretory factor |
קריטריונים לזכאות
גילאים הזכאים ללימודים | 18 Years ל 18 Years |
מינים הזכאים ללימודים | All |
מקבל מתנדבים בריאים | כן |
קריטריונים | 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 |
תוֹצָאָה
מדדי תוצאות ראשוניים
1. Number of participants with treatment-related adverse [Cumulative from day 1 to 80]
2. Number of participants with completion of prescribed Salovum treatment [Cumulative from day 1 to 80]
אמצעי תוצאה משניים
1. Number of participants with altered blood levels of triglycerides and cholesterol [Change from baseline at day 20, 57 and 70.]
2. Number of participants with reduced or no steroid intake [Change from baseline at day 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70.]
3. Number of participants with detetable blood levels antisecretory factor [Change from baseline at day 20, 57 and 70.]
4. Number of participants with altered blood levels of inflammatory cytokines [Change from baseline at day 20, 57 and 70.]
אמצעי תוצאה אחרים
1. Cognitive function [Change from baseline at day 20, 57 and 70.]
2. Number of participants with decreased neurological function [Change from baseline at day 20, 57 and 70.]
3. Number of participants with decreased performance [Change from baseline at day 20, 57 and 70.]
4. Number of participants with decreased quality of life [Change from baseline at day 20, 57 and 70.]