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

Phase 2

Withdrawn

• Conditions: Intensive Care Neurological Disorder; Edema Brain; Head Trauma
• Interventions: Dietary Supplement: Salovum

• Registration Number: NCT03453749
• Lead Sponsor: Peter Siesjö

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.

Study Timeline

• Study First Submitted: 2017-12-13
• Study First Submitted QC: 2018-02-26
• Study Start: 2018-03-01
• Study First Posted: 2018-03-05
• Status Verified: 2018-12
• Primary Completion: 2018-12-10
• Study Completion: 2018-12-10
• Last Update Submitted: 2018-12-10
• Last Update Posted: 2018-12-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
ICP	Up to 7 days	Intracranial pressure in mm Hg

Secondary Outcome Measures

Name	Time	Method
Microdialysis biochemistry	Up to 7 days	Analysis of glucose, pyruvate and lactate from micro-dialysis fluid
PtO2	Up to 7 days	Brain tissue oxygenation in mm Hg
TIL	Up to 7 days	Treatment Intensity Level, scale 0-38
Cytokine expression	Up to 7 days	Analysis of cytokines from micro-dialysis fluid