Anti-secretory Factor as a Treatment for Adults With Severe Traumatic Head Injury

NCT03453749 | Withdrawn Phase 2

• 1 other identifier: Ethics reference: 2013/144
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Head Trauma; Intensive Care Neurological Disorder; Edema Brain

Keywords

Traumatic brain injury; Cerebral edema; Microdialysis; Inflammatory cytokines

Outcome Measures

Primary Outcomes (1)

• ICP

  Intracranial pressure in mm Hg

  Up to 7 days

Secondary Outcomes (4)

• PtO2

  Up to 7 days

• Microdialysis biochemistry

  Up to 7 days

• Cytokine expression

  Up to 7 days

• TIL

  Up to 7 days

Study Arms (1)

Salovum

OTHER

Patients will be given Salovum 1g/kg body weight/24 hours, divided into 6 dosages and given during 5 consecutive days.

Dietary Supplement: Salovum

Interventions

Salovum DIETARY_SUPPLEMENT

Salovum is freeze dried egg yolk, highly enriched with anti-secretory factor. Salovum is registered as a medical food by the EU

Salovum

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• No consent
• Systolic blood pressure below 90 mm Hg post resuscitation
• Epidural hematoma with no other signs of intra-cranial injury
• Penetrating injury

Sponsors & Collaborators

• Peter Siesjö: lead

Related Publications (10)

• 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.

  PMID: 24928077 BACKGROUND

• 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.

  PMID: 24484450 BACKGROUND

• 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.

  PMID: 24294684 BACKGROUND

• 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.

  PMID: 21957667 BACKGROUND

• 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.

  PMID: 20684797 BACKGROUND

• 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.

  PMID: 19479454 BACKGROUND

• 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.

  PMID: 17937690 BACKGROUND

• 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.

  PMID: 14613757 BACKGROUND

• 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.

  PMID: 25248325 BACKGROUND

• 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.

  PMID: 21375367 BACKGROUND

MeSH Terms

Conditions

Craniocerebral Trauma; Brain Edema; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Brain Diseases; Central Nervous System Diseases; Brain Injuries

Study Officials

• David Cederberg, Consultant

  Dept of Neurosurgery, Skane University Hospital, Lund, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Consultant

Model Details: 5 consecutive adult patients with severe head trauma will receive treatment

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: March 5, 2018
• Study Start: March 1, 2018
• Primary Completion: December 10, 2018
• Study Completion: December 10, 2018
• Last Updated: December 12, 2018

Record last verified: 2018-12