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Effect of Antisecretory Factor, Given as a Food Supplement to Adult Patients With Severe Traumatic Brain Injury (SASAT)

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ClinicalTrials.gov Identifier: NCT03339505
Recruitment Status : Recruiting
First Posted : November 13, 2017
Last Update Posted : November 13, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Treatment of increased ICP, using Anti-secretory Factor, in patients with severe head trauma Brain edema, defined as an increased fluid content in either the extracellular or intracellular space, arise in both trauma and in conjunction with other brain pathologies such as infectious diseases, intracranial tumors and ischemic events, i.e. stroke. The mechanisms underlying the formation of edema are not fully understood. In the injured brain, leakage over the blood brain-barrier arise which leads to transport of fluid from the blood to the extracellular space, causing an extracellular or vasogenic edema. Damage to cell membranes and disruption of cell function causes an intracellular or cytotoxic edema. Although one type of edema may predominate initially, one type most likely leads to another. In addition to the physiological, flow-related changes that arise, the edema is also worsened by the inflammatory response to damage. In the injured brain, disease associated molecular patterns (DAMP), and pro-inflammatory cytokines that can give rise to both intracellular and extracellular edema are released.

If the edema becomes expansive enough to give rise to a significant increase in intracranial pressure the circulation of the brain is threatened and surgical intervention inevitable. The most common procedure is hemicraniectomy, a procedure intended to add more space for the edematous brain to expand. The procedure itself is risky, and re-operations due to hematoma, CSF-leakage and more are common. Furthermore, it is not known how the procedure itself affects the brain in terms of increased edema, tearing of the brain etc.

Antisecretory factor, AF is a 41 kDa protein that exists in most mammals. It was first discovered due to its ability to inhibit experimental diarrhea. Endogenous AF secretion increases after exposure to bacterial toxins and an increase in AF secretion in combination with an inflammatory reaction may be a part of normal defense against the secretory and inflammatory component in diarrhea and other pathological processes involving membrane leakage and inflammation. AF has been shown to modulate pro-inflammatory and anti- inflammatory cytokine release. AF has also been shown to be effective against vertigo symptoms in Meniere's disease, which is believed to be caused by an abnormal collection of lymph around the balance nerve. AF and AF16 (the functional terminal 16 amino-acid peptide) have been tested in animal models of cerebral edema such as herpes encephalitis and traumatic brain injury with significant reduction of intracranial pressure, morbidity and mortality AF is commercially available for human use as Salovum®, an egg yolk powder B221® enriched for AF. It is available in pharmacies without prescription, but can also be prescribed as a dietary supplement in Sweden. Salovum® is classified as a "medical food" by the Swedish Pharmaceutical Agency and the European Union. Salovum® is currently registered in the Republic of South Africa.

Hypothesis Cerebral edema in traumatic brain injury is caused by inflammation triggered by tissue damage. The anti-secretory and anti-inflammatory compound Salovum® has the potential to counteract this and thus reduce cerebral edema in traumatic brain injury. Furthermore, the reduction of cerebral edema is hypothesized to decrease intracranial pressure, reduce the development of secondary brain damage and subsequently reduce treatment intensity levels and death.

Aims and Objectives Though, the number of patients with severe traumatic head injury in Sweden is decreasing and the need for a larger, randomized trial in a centre with large volumes of traumatic brain injury is needed The primary focus for scientific investigation is to evaluate if AF given as a dietary supplement (Salovum®) will reduce 30-day mortality in adult patients with severe traumatic brain injury. The secondary aims are to investigate whether AF will reduce intracranial pressure and treatment intensity levels - TIL, during intervention.

Methodology The outlined study is a phase-2, prospective, double-blinded, randomized, placebo-controlled trial. After inclusion patients will be randomized to active Salovum® or placebo egg powder treatment every 4th hour during 5 days. Treatment of patients will be according to current algorithms at the study site.

Study population 100 adult (age 18+) patients with severe traumatic brain injury, where ICP-monitoring is deemed necessary, will be included in the study.

Patient samples A venous whole blood sample will be drawn before and after treatment in all patients. The blood sample will be frozen and stored at the study site for further analysis.

Anticipated benefits In an ongoing Swedish study, preliminary results indicate that AF has a very potent ICP- lowering effect in patients with severe TBI and other pathologies encompassing cerebral edema, which might prove an effect on 30-day mortality in this trial.


Condition or disease Intervention/treatment Phase
Brain Trauma Dietary Supplement: Salovum Dietary Supplement: Placebo Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blinded until the end of the trial. Unmasking will take place once all patients are included and the trial is concluded.
Primary Purpose: Treatment
Official Title: Salovum (Antisecretory Factor) in Patients With Severe Traumatic Brain Injury
Actual Study Start Date : September 17, 2017
Estimated Primary Completion Date : March 17, 2019
Estimated Study Completion Date : April 30, 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Treatment group
Patients in treatment group will receive Salovum according to g/kg body weight/24 hours/divided into 6 doses, during a maximum of 5 days
Dietary Supplement: Salovum
Dietary supplement with high concentration of anti-secretory factor
Placebo Comparator: Placebo group
Patients in treatment group will receive Placebo (egg yolk powder) according to g/kg body weight/24 hours/divided into 6 doses, during a maximum of 5 days
Dietary Supplement: Placebo
Placebo for Salovum


Outcome Measures

Primary Outcome Measures :
  1. 30 day mortality [ Time Frame: 30 days ]
    Death within 30 days of trauma


Secondary Outcome Measures :
  1. TIL - Treatment Intensity Level [ Time Frame: 0-5 days ]
    TIL is scored at the end of each 24 hour period in the NICU, where 0 is lowest intensity and 38 is maximum intensity

  2. ICP - Intracranial Pressure [ Time Frame: 0-5 days ]
    ICP in mm Hg is recorded every hour during 0-5 days


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult of either gender between 18 and 65 years.
  2. Non-penetrating, isolated severe traumatic brain injury
  3. GCS >3 and GCS<9 on admission or within 48 hours after injury*
  4. Admission to study hospital within 24 hours of injury*
  5. No known history of allergy to egg-protein
  6. Planned for intracranial pressure monitoring
  7. Absence of bilaterally dilated pupils
  8. 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:

1. No consent 2. Systolic blood pressure below 90 mm Hg post resuscitation 3. Epidural hematoma with no other signs of intra-cranial injury 4. Penetrating injury 5. Non-fulfillment of inclusion criteria after screening and inclusion procedures.

Contacts and Locations

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): NCT03339505


Contacts
Contact: Peter Siesjö, Professor 0046705655778 peter.siesjo@med.lu.se
Contact: David Cederberg, MD 0046702060344 david.cederberg@med.lu.se

Locations
South Africa
Department of Neurosurgery, Tygerberg Hospital, Francie Van Zijl Dr Recruiting
Cape Town, South Africa, 7505
Contact: Adriaan J Vlok, Professor    0027(0)219389265    ianvlok@sun.ac.za   
Principal Investigator: Adriaan J Vlok, Professor         
Sponsors and Collaborators
Peter Siesjö
University of Stellenbosch
Investigators
Principal Investigator: Adriaan J Vlok, Professor University of Stellenbosch
More Information

Publications:

Responsible Party: Peter Siesjö, Professor, Consultant, Skåne University Hospital
ClinicalTrials.gov Identifier: NCT03339505     History of Changes
Other Study ID Numbers: Ethics Reference #: M16/10/040
First Posted: November 13, 2017    Key Record Dates
Last Update Posted: November 13, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Brain Injuries, Traumatic
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Antisecretory factor
Antidiarrheals
Gastrointestinal Agents