Investigation of Thermal Injury on Intestinal Permeability in Both Thermal Injury and Healthy Participants
Condition: Burns
MeSH terms: Burns
Intervention: Lactulose and Mannitol solution; Sucralose
Intervention description: Participants will receive 100 milliliter (mL) oral solution of Lactulose [5 grams (g)]/ Mannitol (2g), a non-investigational medicinal product, by oral route to measure intestinal permeability.; Participants will receive 3 capsules of Sucralose (2g), a non-investigational medicinal product, by oral route to measure intestinal permeability.
Intervention MeSH terms: Mannitol; Lactulose
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Mannitol; Intestinal permeability; Thermal injury; HESTIA; Sucralose; Lactulose

Summary:

      This longitudinal, prospective study aims to establish the magnitude and time course of
      changes in intestinal permeability; establish the optimal method for assessment of intestinal
      permeability in thermally injured participants: describe the participant population most
      likely to benefit from a new medicinal product which could prevent changes in intestinal
      permeability; and improve our understanding of the links between intestinal damage, changes
      in the gut microbiome and microbial translocation to the systemic circulation following
      thermal injury. The key factors of interest in this study are to understand the impact of
      thermal injury on intestinal permeability in thermally injured participants compared to
      healthy participants; and to understand the changes in intestinal permeability over time.
      Approximately 15 eligible healthy participants and 25 thermally injury participants will be
      included. The sugar test material (STM) comprises of Lactulose, Mannitol and Sucralose and
      will be intermittently administered enterally to all the participants. The full duration of
      the study for healthy participants will be approximately two weeks and 6 months for thermally
      injured participants. In order to enter this study thermally injured participants will be
      required to co-enroll in this study and an allied study entitled: A Multi-center, Prospective
      Study to Examine the Relationship between Neutrophil Function and Sepsis in Adults and
      Children with Severe Thermal Injury (SIFTI-2). (reference number IRAS ID: 200366).
    

Eligibility criteria:

        Inclusion Criteria:

        For Healthy participants:

          -  Males or females must be greater than or equal to 18 years of age at the time of
             signing informed consent.

          -  Participants who are healthy as determined by the investigator following medical
             evaluation including medical history, physical examination, and laboratory tests.

          -  A female participant is eligible to participate if she is not pregnant (negative
             pregnancy testing at screening or Day 1 as needed) and not breastfeeding.

          -  Capable of giving signed informed consent.

        For Thermally injured participants:

          -  Participants must be greater than or equal to 18 years of age.

          -  Participants who have sustained a burn (thermal injury) with a Total Burn Surface Area
             (TBSA) greater than or equal to 15 percent.

          -  Admission to the burn center (study site) less than or equal to 24 hours following
             injury.

          -  Able to take enteral fluids either orally or via a nasogastric tube (depends on facial
             burn damage).

          -  A female participant is eligible to participate if she is not pregnant (negative
             pregnancy testing at study entry) and not breastfeeding.

        Exclusion Criteria

        For Healthy participants:

          -  Healthy participants are excluded from this study if they are receiving
             anti-coagulation therapy.

          -  Pregnancy or breastfeeding.

          -  A body mass index greater than 34 kilogram per meter square (kg/m^2).

          -  An active history of alcohol dependency.

          -  History of sensitivity to any of the STM, or components thereof or a history of drug
             or other allergy that, in the opinion of the Investigator and/or GlaxoSmithKline (GSK)
             Medical Monitor, contraindicates their participation.

          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody and
             confirmatory Hepatitis C Polymerase Chain Reaction (PCR) result within 3 months of
             screening.

          -  A positive pre-study urine drug/alcohol screen.

          -  A positive test for Human Immuno-deficiency Virus (HIV) antibody.

          -  Participants unable to swallow large capsules (the capsules will be shown to
             participants at screening).

          -  Galactosaemia or severe lactose intolerance.

          -  Use of an antibiotic 2 weeks prior to study start (administration of the STM).

          -  Gastroenteritis in the 2 weeks prior to study start (administration of the STM).

        For thermally injured participants:

          -  Chemical or electrical burn.

          -  Multiple traumatic injuries with an Injury Severity Score (ISS) more than or equal to
             16.

          -  Participants received substantial undocumented management prior to arrival at the
             study site (burn center) e.g. from paramedics or in a local accident and emergency
             department.

          -  Systemic corticoidsteroid use.

          -  Intravenous (IV) Mannitol use.

          -  HIV infection.

          -  Viral Hepatitis B or C infection.

          -  Gastrointestinal disease (e.g. inflammatory bowel disease) which may affect intestinal
             permeability.

          -  Previous bowel resection (e.g. hemicolectomy, small bowel resection).

          -  Galactosaemia or severe lactose intolerance.

          -  Bowel obstruction.

          -  Renal dysfunction requiring renal replacement therapy (end-stage renal failure prior
             to thermal injury).

          -  Active autoimmune disease and receiving immunomodulatory therapy e.g. rheumatoid
             arthritis anti-Tumor Necrosis Factor (TNF).

          -  Active chemotherapy for cancers or immunoremittive therapies (prednisolone,
             Adalimumab) within 60 days of thermal injury.

          -  Premorbid conditions of malignancy currently under treatment.

          -  Previous bilateral lower extremity amputation.

          -  Decision not to treat the participant due to futility.