Antisecretory Factor in Primary Glioblastoma 1
Condition: Glioblastoma; Cerebral Edema; Chemotherapy Effect
MeSH terms: Glioblastoma; Brain Edema
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Salovum
Intervention type(s): Dietary Supplement
Intervention description(s): Egg yolk powder enriched for anti secretory factor
Other intervention name(s): Antisecretory factor
Intervention MeSH terms: Antisecretory factor
Intervention model: Single Group Assignment
Intervention model description: Phase 1-2, open label, single arm, single center.
Masking: None (Open Label)
Primary purpose: Treatment