A Prospective, Longitudinal Study to Investigate the Effect of Thermal Injury on Intestinal Permeability and Systemic Inflammation (HESTIA)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Burns
- Sponsor
- GlaxoSmithKline
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol on Day 1
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief 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).
Investigators
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).
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol on Day 1
Time Frame: 0 to 5 hours and 0 to 24 hours on Day 1
Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. The impact of injury in thermal injury participants was compared with healthy participants using L/M ratio in urine.
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants
Time Frame: 0 to 5 hours and 0 to 24 hours on Day 8 and Day 15
Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Time Frame: 0 to 5 hours on Days 3, 5, 7, 11, 13 and 0 to 24 hours on Days 3, 5, 7, 9, 11 and 13
Urine samples were collected at indicated time-points to determine the impact of thermal injury on the magnitude of small intestine permeability following the injury. As, L/M does not get metabolized, it gets filtered in the kidney and excreted in the urine. Baseline value was considered as Day 1 for both the groups. Change from Baseline is equal to post-Baseline visit value minus Baseline value.