Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Antisecretory Factor In Severe Traumatic Brain Injury (AFISTBI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04117672
Recruitment Status : Not yet recruiting
First Posted : October 7, 2019
Last Update Posted : October 7, 2019
Sponsor:
Collaborators:
Skane University Hospital
Lantmannen Medical AB
Information provided by (Responsible Party):
Peter Siesjö, Skane University Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Dietary Supplement: Salovum Dietary Supplement: Placebo egg yolk powder Phase 2

Detailed Description:

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)


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants with severe TBI and scheduled for multimodal monitoring will be randomised to active or placebo treatment.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Egg powder enriched for antisecretory factor and placebo egg powder with the same color, taste and texture,
Primary Purpose: Treatment
Official Title: Evaluation of Antisecretory Factor in Treatment of Severe Traumatic Brain Injury With Multimodal Monitoring
Estimated Study Start Date : November 1, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Egg yolk powder not enriched for antisecretory powder
Dietary Supplement: Placebo egg yolk powder
Normal egg yolk powder

Experimental: Salovum
Egg yolk powder enriched for antisecretory powder
Dietary Supplement: Salovum
Active egg yolk powder
Other Name: Antisecretory factor




Primary Outcome Measures :
  1. ICP mean [ Time Frame: Change from baseline during intervention ]
    Measured by an intracranial pressure sensor

  2. ICP area under curve [ Time Frame: Change from baseline during intervention ]
    Measured by an intracranial pressure sensor

  3. ICP mean [ Time Frame: During intervention, 5 days ]
    Measured by an intracranial pressure sensor

  4. ICP area under curve [ Time Frame: During intervention, 5 days ]
    Measured by an intracranial pressure sensor

  5. Treatment intensity level [ Time Frame: Change from baseline during intervention ]
    Treatment intensity level (TIL) scale. Minimum 0 (no intervention to control intracranial pressure (ICP)), maximum 38 points (maximum efforts to control ICP)

  6. Treatment intensity level [ Time Frame: During intervention, 5 days ]
    Treatment intensity level (TIL) scale. Minimum 0 (no intervention to control intracranial pressure (ICP)), maximum 38 points (maximum efforts to control ICP)


Secondary Outcome Measures :
  1. Intracerebral oxygen partial pressure [ Time Frame: Change from baseline during intervention ]
    Measured by an intracranial oxygen sensor

  2. Intracerebral oxygen partial pressure [ Time Frame: During intervention, 5 days ]
    Lactate/pyruvate ratio assessed by online microdialysis

  3. Rate of cerebral metabolism [ Time Frame: Change from baseline during intervention ]
    Lactate/pyruvate ratio assessed by online microdialysis

  4. Rate of cerebral metabolism [ Time Frame: During intervention, 5 days ]
    Lactate/pyruvate ratio assessed by online microdialysis


Other Outcome Measures:
  1. Inflammatory cytokine secretion [ Time Frame: Change from baseline during intervention ]
    Interleukin-6 (Il-6), interleukin-8 (IL-8) and monocyte chemotactic protein (MCP-1) assessed from microdialysate and plasma by multiplex analysis

  2. Concentration of inflammatory cytokines [ Time Frame: During intervention, 5 days ]
    Interleukin-6 (Il-6), interleukin-8 (IL-8) and monocyte chemotactic protein (MCP-1) assessed from microdialysate and plasma by multiplex analysis

  3. Mortality [ Time Frame: At 30 days and 12 months ]
    Mortality due to traumatic brain injury

  4. Disability [ Time Frame: At 6 and 12 months ]
    Assessed by Glagow Outcome Scale-Extended (GOSE). Minimum 1 (full recovery). MAXIMUM 8 (DEAD)

  5. Concentration of brain damage markers [ Time Frame: Change from baseline during intervention ]
    Glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) assessed from microdialysate and plasma

  6. Concentration of brain damage markers [ Time Frame: During intervention, 5 days ]
    Glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) assessed from microdialysate and plasma



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   10 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04117672


Contacts
Layout table for location contacts
Contact: Peter Siesjö, MD, PhD +4646171274 peter.siesjo@med.lu.se
Contact: David Cederberg, MD +4646177655 david.cederberg@med.lu.se

Locations
Layout table for location information
Sweden
Skane University Hopsital Not yet recruiting
Lund, Sweden, 22185
Contact: David Cederberg, MD       david.cederberg@med.lu.se   
Sponsors and Collaborators
Peter Siesjö
Skane University Hospital
Lantmannen Medical AB
Investigators
Layout table for investigator information
Principal Investigator: Peter Siesjö, MD, PhD Skane University Hospital

Publications:

Layout table for additonal information
Responsible Party: Peter Siesjö, Professor, Skane University Hospital
ClinicalTrials.gov Identifier: NCT04117672     History of Changes
Other Study ID Numbers: 2019-00553
First Posted: October 7, 2019    Key Record Dates
Last Update Posted: October 7, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual patient data that underlie published results will be made available after publication.after de identification.
Supporting Materials: Study Protocol
Time Frame: From 3 months after publication to 24 months after publication.
Access Criteria: Anyone who wishes to access the data.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Peter Siesjö, Skane University Hospital:
traumatic brain injury
cerebral edema
antisecretory factor
inflammatory cytokines
cerebral oxygen monitoring
intracranial pressure
microdialysis
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
Craniocerebral Trauma
Trauma, Nervous System
Central Nervous System Diseases
Nervous System Diseases
Antisecretory factor
Antidiarrheals
Gastrointestinal Agents