Anti-secretory Factor as a Treatment for Adults With Severe Traumatic Head Injury (SATSWEDEN)
Primary Purpose
Head Trauma, Intensive Care Neurological Disorder, Edema Brain
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Salovum
Sponsored by
About this trial
This is an interventional treatment trial for Head Trauma focused on measuring Traumatic brain injury, Cerebral edema, Microdialysis, Inflammatory cytokines
Eligibility Criteria
Inclusion Criteria:
- Adult of either gender between 18 and 65 years.
- Non-penetrating, isolated severe traumatic brain injury
- GCS >3 and GCS<9 on admission or within 48 hours after injury*
- Admission to study hospital within 24 hours of injury*
- No known history of allergy to egg-protein
- Planned for intracranial pressure monitoring
- Absence of bilaterally dilated pupils
CT scan with traumatic pathology that is more than an isolated epidural hematoma
- Within 24 hours of injury (for patients with GCS < 9 on admission) or Within 24 hours of deterioration (among patients deteriorating to GCS < 9 within 48 hours of injury)
Exclusion Criteria:
- No consent
- Systolic blood pressure below 90 mm Hg post resuscitation
- Epidural hematoma with no other signs of intra-cranial injury
- Penetrating injury
- Non-fulfillment of inclusion criteria after screening and inclusion procedures.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Salovum
Arm Description
Patients will be given Salovum 1g/kg body weight/24 hours, divided into 6 dosages and given during 5 consecutive days.
Outcomes
Primary Outcome Measures
ICP
Intracranial pressure in mm Hg
Secondary Outcome Measures
PtO2
Brain tissue oxygenation in mm Hg
Microdialysis biochemistry
Analysis of glucose, pyruvate and lactate from micro-dialysis fluid
Cytokine expression
Analysis of cytokines from micro-dialysis fluid
TIL
Treatment Intensity Level, scale 0-38
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03453749
Brief Title
Anti-secretory Factor as a Treatment for Adults With Severe Traumatic Head Injury
Acronym
SATSWEDEN
Official Title
Anti-secretory Factor as a Treatment for Adults With Severe Traumatic Head Injury
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Withdrawn
Why Stopped
New study in planning
Study Start Date
March 1, 2018 (Anticipated)
Primary Completion Date
December 10, 2018 (Actual)
Study Completion Date
December 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Peter Siesjö
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Introduction/Background Brain swelling/brain edema can occur due to many pathologies of the brain, such as infections, ischemia and trauma.
The edema can be either primarily intra-cellular or extra-cellular. The mechanisms by which edema arise are not fully known but it is proposed that inside the damaged brain, fluid will pass over the blood-brain barrier of the vessels into the extra-cellular space. The accumulation of fluid will lead to an increase in distance between the cell and its closest capillary, which may lead to energy failure and intra-cellular edema. The extra volume of the fluid leads to increased intracranial pressure, which in turn leads to an increase in blood pressure, aggravating the edema. In addition to the physiological changes that occur, the edema will be increased by the immunological response to the tissue damage with release of pro-inflammatory cytokines that give rise to both extra- and intra-cellular edema.
Today, no treatment has been proven efficient against traumatic brain edema. AF - anti-secretory factor is a 41 kDa protein that exists in humans and most animals. It was discovered due to its ability to inhibit experimental diarrhea.
AF has been proven to have an effect on Mb Menière and glaucoma. In animal models, AF has been proven efficient in reducing increased intracranial pressure caused by trauma and virus infection in the brain.
Salovum®, an egg yolk powder enriched in AF, is registered in the European Union as a medical food.
Methods: 5 adult patients with severe traumatic brain injury will be included in the trial via next of kin consent.
Medical interventions are protocol based. The protocol includes first, second and third treatment levels.
Patients included in the trial, will receive two micro-dialysis (MD) catheters in addition to standard treatment. One catheter will be placed in a separate burr hole close to the ICP and LICOX catheter, the other MD catheter will be placed in vicinity of the damaged barin tissue.
Patients will receive Salovum® 6 hours after trial inclusion. Patient dosage is 1g/kg body weight/24 hours, divided into 6 doses and administered orally, via tubing every 4 hours for 5 consecutive days.
Objective: Primary end-point is to investigate if Salovum® has a beneficiary effect on ICP.
Secondary endpoints are to investigate if Salovum® has a beneficiary effect on treatment intensity levels (TIL), brain-oxygenation, microdialysis bio-chemistry and cytokine expression in plasma and microdialysate.
Detailed Description
MD will be analysed bedside hourly for patient management, and the remaining MD samples will be frozen in -70° C for later analysis of cytokines.
An extra blood sample will be drawn twice daily, blood will be centrifuged and plasma will be frozen in -70° C for later analysis of cytokines.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head Trauma, Intensive Care Neurological Disorder, Edema Brain
Keywords
Traumatic brain injury, Cerebral edema, Microdialysis, Inflammatory cytokines
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
5 consecutive adult patients with severe head trauma will receive treatment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Salovum
Arm Type
Other
Arm Description
Patients will be given Salovum 1g/kg body weight/24 hours, divided into 6 dosages and given during 5 consecutive days.
Intervention Type
Dietary Supplement
Intervention Name(s)
Salovum
Intervention Description
Salovum is freeze dried egg yolk, highly enriched with anti-secretory factor. Salovum is registered as a medical food by the EU
Primary Outcome Measure Information:
Title
ICP
Description
Intracranial pressure in mm Hg
Time Frame
Up to 7 days
Secondary Outcome Measure Information:
Title
PtO2
Description
Brain tissue oxygenation in mm Hg
Time Frame
Up to 7 days
Title
Microdialysis biochemistry
Description
Analysis of glucose, pyruvate and lactate from micro-dialysis fluid
Time Frame
Up to 7 days
Title
Cytokine expression
Description
Analysis of cytokines from micro-dialysis fluid
Time Frame
Up to 7 days
Title
TIL
Description
Treatment Intensity Level, scale 0-38
Time Frame
Up to 7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult of either gender between 18 and 65 years.
Non-penetrating, isolated severe traumatic brain injury
GCS >3 and GCS<9 on admission or within 48 hours after injury*
Admission to study hospital within 24 hours of injury*
No known history of allergy to egg-protein
Planned for intracranial pressure monitoring
Absence of bilaterally dilated pupils
CT scan with traumatic pathology that is more than an isolated epidural hematoma
Within 24 hours of injury (for patients with GCS < 9 on admission) or Within 24 hours of deterioration (among patients deteriorating to GCS < 9 within 48 hours of injury)
Exclusion Criteria:
No consent
Systolic blood pressure below 90 mm Hg post resuscitation
Epidural hematoma with no other signs of intra-cranial injury
Penetrating injury
Non-fulfillment of inclusion criteria after screening and inclusion procedures.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Cederberg, Consultant
Organizational Affiliation
Dept of Neurosurgery, Skane University Hospital, Lund, Sweden
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
24928077
Citation
Eide PK, Eidsvaag VA, Hansson HA. Antisecretory factor (AF) exerts no effects on intracranial pressure (ICP) waves and ICP in patients with idiopathic normal pressure hydrocephalus and idiopathic intracranial hypertension. J Neurol Sci. 2014 Aug 15;343(1-2):132-7. doi: 10.1016/j.jns.2014.05.054. Epub 2014 Jun 2.
Results Reference
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PubMed Identifier
24484450
Citation
Zaman S, Aamir K, Lange S, Jennische E, Silfverdal SA, Hanson LA. Antisecretory factor effectively and safely stops childhood diarrhoea: a placebo-controlled, randomised study. Acta Paediatr. 2014 Jun;103(6):659-64. doi: 10.1111/apa.12581. Epub 2014 Mar 10.
Results Reference
background
PubMed Identifier
24294684
Citation
Leong SC, Narayan S, Lesser TH. Antisecretory factor-inducing therapy improves patient-reported functional levels in Meniere's disease. Ann Otol Rhinol Laryngol. 2013 Oct;122(10):619-24.
Results Reference
background
PubMed Identifier
21957667
Citation
Alam NH, Ashraf H, Olesen M, Salam MA, Gyr N, Meier R. Salovum egg yolk containing antisecretory factor as an adjunct therapy in severe cholera in adult males: a pilot study. J Health Popul Nutr. 2011 Aug;29(4):297-302. doi: 10.3329/jhpn.v29i4.8443.
Results Reference
background
PubMed Identifier
20684797
Citation
Ulgheri C, Paganini B, Rossi F. Antisecretory factor as a potential health-promoting molecule in man and animals. Nutr Res Rev. 2010 Dec;23(2):300-13. doi: 10.1017/S0954422410000193. Epub 2010 Aug 5.
Results Reference
background
PubMed Identifier
19479454
Citation
Hanner P, Rask-Andersen H, Lange S, Jennische E. Antisecretory factor-inducing therapy improves the clinical outcome in patients with Meniere's disease. Acta Otolaryngol. 2010 Feb;130(2):223-7. doi: 10.3109/00016480903022842.
Results Reference
background
PubMed Identifier
17937690
Citation
Zaman S, Mannan J, Lange S, Lonnroth I, Hanson LA. B 221, a medical food containing antisecretory factor reduces child diarrhoea: a placebo controlled trial. Acta Paediatr. 2007 Nov;96(11):1655-9. doi: 10.1111/j.1651-2227.2007.00488.x.
Results Reference
background
PubMed Identifier
14613757
Citation
Laurenius A, Wangberg B, Lange S, Jennische E, Lundgren BK, Bosaeus I. Antisecretory factor counteracts secretory diarrhoea of endocrine origin. Clin Nutr. 2003 Dec;22(6):549-52. doi: 10.1016/s0261-5614(03)00057-8.
Results Reference
background
PubMed Identifier
25248325
Citation
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.
Results Reference
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PubMed Identifier
21375367
Citation
Al-Olama M, Wallgren A, Andersson B, Gatzinsky K, Hultborn R, Karlsson-Parra A, Lange S, Hansson HA, Jennische E. The peptide AF-16 decreases high interstitial fluid pressure in solid tumors. Acta Oncol. 2011 Oct;50(7):1098-104. doi: 10.3109/0284186X.2011.562240. Epub 2011 Mar 4.
Results Reference
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Anti-secretory Factor as a Treatment for Adults With Severe Traumatic Head Injury
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