Antisecretory Factor In Severe Traumatic Brain Injury

NCT ID: NCT04117672

Last Updated: 2026-01-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-10

Study Completion Date

2027-06-30

Brief Summary

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This study evaluates the addition of Salovum, an egg yolk powder enriched for antisecretory factor, to standard care of participants with severe traumatic brain injury. Half of the participants will be administered Salovum while the other half will be given a placebo egg yolk powder, not enriched for antisecretory factor. Intracranial pressure (ICP), partial brain oxygen pressure (PtbO2), microdialysis of metabolites and inflammatory mediators and trauma intensity level (TIL) will be assessed in all patients.

Detailed Description

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Cerebral edema accounts for an essential part of the morbidity and mortality in severe traumatic brain injury but can also arise in other cerebral pathologies such as infectious and ischemic conditions such e.g. stroke and meningitis. Cerebral edema can lead to an elevated intracranial pressure (ICP) with impact on both perfusion and diffusion in the brain.

AF (antisecretory factor) is a 41 kilodalton endogenous and essential protein with proposed antisecretory and anti-inflammatory effects. AF is homologous to S5A and Rpn10 proteins which are parts of the 26S proteasome subunit. AF also shows close homology to angiocidin a protein with reported anti-proliferative and anti-angiogenic properties. The AF protein is cleaved into several active peptides, one of which has been synthesized within a 16 amino acid peptide (AF-16) that has been used in animal experimental studies. Salovum® is a product based on the egg yolk powder B221®, and contains high levels of AF. Salovum® is classified as a food for special medical purposes (FSMP) by the European Food Safety Agency.

AF has shown clinical effects in Mb Ménière, mastitis and meningitis. Experimentally AF-16 and AF have been shown to reduce intracranial pressure and improve outcome in models of traumatic brain injury (TBI) and herpes encephalitis. Preliminary results show reduction of ICP and improved outcome in human traumatic brain injury. A randomized, prospective, double-blinded phase 2-3 in participants with severe traumatic head injury is ongoing at Tygerberg University Hospital, Cape Town, South Africa (ClinicalTrials.gov identification number: NCT03339505).

The antisecretory factor is an endogenous protein and no antibody formation has been demonstrated in human administration. Although Salovum® has been given to hundreds of patients, no side effects have been recorded. Egg yolk allergy is a contraindication but no cases of triggered allergy have been reported.

The mechanisms underlying the effects of antisecretory factor on cerebral edema are not clarified. Immune modulation through effects on myeloid cells, proteasome modulation and effects on ion pumps have been proposed.

The present study intends to clarify mechanisms behind the proposed effect of antisecretory factor in cerebral edema In the present study participants with severe traumatic brain injury as defined in inclusion and exclusion criteria will be randomised to either treatment with Salovum or placebo egg powder during 5 days after enrolment. Randomisation will be performed in blocks and randomisation envelopes will be used with the number inside the envelope. Salovum and normal egg powder will be suspended with tap water and administered through the gastric feeding tube. All participants will receive standard care for severe TBI according to the treatment algorithm at the Neuro Intensive Care Unit (NICU), Department of Neurosurgery, Skåne University Hospital, Lund, Sweden. The algorithm prescribes invasive monitoring of ICP, PtbO2 and metabolites (cerebral microdialysis). As this algorithm includes stepwise co-interventions in order to control ICP and cerebral perfusion pressure (CPP) the TIL score will be used to compensate for the bias of increased co-interventions in either arm. At follow up patients will be assessed for mortality and Glasgow Outcome Scale-Extended (GOSE)

Conditions

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Traumatic Brain Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants with severe TBI and scheduled for multimodal monitoring will be randomised to active or placebo treatment.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Egg powder enriched for antisecretory factor and placebo egg powder with the same color, taste and texture,

Study Groups

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Placebo

Egg yolk powder not enriched for antisecretory powder

Group Type PLACEBO_COMPARATOR

Placebo egg yolk powder

Intervention Type DIETARY_SUPPLEMENT

Normal egg yolk powder

Salovum

Egg yolk powder enriched for antisecretory powder

Group Type EXPERIMENTAL

Salovum

Intervention Type DIETARY_SUPPLEMENT

Active egg yolk powder

Interventions

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Salovum

Active egg yolk powder

Intervention Type DIETARY_SUPPLEMENT

Placebo egg yolk powder

Normal egg yolk powder

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Antisecretory factor

Eligibility Criteria

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Inclusion Criteria

Severe traumatic brain injury, Glasgow Outcome Scale (GCS) \<9 at admission to NICU.

Clinical indication for insertion of intracranial pressure monitor, intracerebral oxygen pressure monitor and microdialysis catheter.

Consultation with relatives or consent from guardians.

Exclusion Criteria

Known egg yolk allergy.

Unilateral or bilateral fixed and dilated pupil after initial operative intervention.
Minimum Eligible Age

10 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Skane University Hospital

OTHER

Sponsor Role collaborator

Lantmannen Medical AB

OTHER

Sponsor Role collaborator

Peter Siesjö

OTHER

Sponsor Role lead

Responsible Party

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Peter Siesjö

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Peter Siesjö, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Skane University Hospital

Locations

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Skane University Hopsital

Lund, , Sweden

Site Status RECRUITING

Countries

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Sweden

Central Contacts

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Peter Siesjö, MD, PhD

Role: CONTACT

+4646171274

David Cederberg, MD

Role: CONTACT

+4646177655

Facility Contacts

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David Cederberg, MD

Role: primary

References

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Ilkhanizadeh S, Sabelstrom H, Miroshnikova YA, Frantz A, Zhu W, Idilli A, Lakins JN, Schmidt C, Quigley DA, Fenster T, Yuan E, Trzeciak JR, Saxena S, Lindberg OR, Mouw JK, Burdick JA, Magnitsky S, Berger MS, Phillips JJ, Arosio D, Sun D, Weaver VM, Weiss WA, Persson AI. Antisecretory Factor-Mediated Inhibition of Cell Volume Dynamics Produces Antitumor Activity in Glioblastoma. Mol Cancer Res. 2018 May;16(5):777-790. doi: 10.1158/1541-7786.MCR-17-0413. Epub 2018 Feb 5.

Reference Type BACKGROUND
PMID: 29431617 (View on PubMed)

Clausen F, Hansson HA, Raud J, Marklund N. Intranasal Administration of the Antisecretory Peptide AF-16 Reduces Edema and Improves Cognitive Function Following Diffuse Traumatic Brain Injury in the Rat. Front Neurol. 2017 Feb 14;8:39. doi: 10.3389/fneur.2017.00039. eCollection 2017.

Reference Type BACKGROUND
PMID: 28261150 (View on PubMed)

Lonnroth I, Oshalim M, Lange S, Johansson E. Interaction of Proteasomes and Complement C3, Assay of Antisecretory Factor in Blood. J Immunoassay Immunochem. 2016;37(1):43-54. doi: 10.1080/15321819.2015.1042544.

Reference Type BACKGROUND
PMID: 25897558 (View on PubMed)

Al-Olama M, Lange S, Lonnroth I, Gatzinsky K, Jennische E. Uptake of the antisecretory factor peptide AF-16 in rat blood and cerebrospinal fluid and effects on elevated intracranial pressure. Acta Neurochir (Wien). 2015 Jan;157(1):129-37. doi: 10.1007/s00701-014-2221-7. Epub 2014 Sep 24.

Reference Type BACKGROUND
PMID: 25248325 (View on PubMed)

Johansson E, Al-Olama M, Hansson HA, Lange S, Jennische E. Diet-induced antisecretory factor prevents intracranial hypertension in a dosage-dependent manner. Br J Nutr. 2013 Jun 28;109(12):2247-52. doi: 10.1017/S0007114512004552. Epub 2012 Nov 16.

Reference Type BACKGROUND
PMID: 23153478 (View on PubMed)

Hansson HA, Al-Olama M, Jennische E, Gatzinsky K, Lange S. The peptide AF-16 and the AF protein counteract intracranial hypertension. Acta Neurochir Suppl. 2012;114:377-82. doi: 10.1007/978-3-7091-0956-4_73.

Reference Type BACKGROUND
PMID: 22327727 (View on PubMed)

Jennische E, Bergstrom T, Johansson M, Nystrom K, Tarkowski A, Hansson HA, Lange S. The peptide AF-16 abolishes sickness and death at experimental encephalitis by reducing increase of intracranial pressure. Brain Res. 2008 Aug 28;1227:189-97. doi: 10.1016/j.brainres.2008.05.083. Epub 2008 Jun 11.

Reference Type BACKGROUND
PMID: 18586012 (View on PubMed)

Lange S, Lonnroth I. The antisecretory factor: synthesis, anatomical and cellular distribution, and biological action in experimental and clinical studies. Int Rev Cytol. 2001;210:39-75. doi: 10.1016/s0074-7696(01)10003-3.

Reference Type BACKGROUND
PMID: 11580208 (View on PubMed)

Johansson E, Lonnroth I, Lange S, Jonson I, Jennische E, Lonnroth C. Molecular cloning and expression of a pituitary gland protein modulating intestinal fluid secretion. J Biol Chem. 1995 Sep 1;270(35):20615-20. doi: 10.1074/jbc.270.35.20615.

Reference Type BACKGROUND
PMID: 7657640 (View on PubMed)

Reen L, Cederberg D, Marklund N, Visse E, Siesjo P. Antisecretory factor in severe traumatic brain injury (AFISTBI): protocol for an exploratory randomized placebo-controlled trial. Trials. 2025 Feb 7;26(1):43. doi: 10.1186/s13063-025-08760-7.

Reference Type DERIVED
PMID: 39920739 (View on PubMed)

Other Identifiers

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2019-00553

Identifier Type: -

Identifier Source: org_study_id

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