Investigation of Thermal Injury on Intestinal Permeability in Both Thermal Injury and Healthy Participants

NCT03242434 | Terminated Phase 1 Results

• 1 other identifier: 206243
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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).

Conditions

Burns

Keywords

Mannitol; Intestinal permeability; Thermal injury; HESTIA; Sucralose; Lactulose

Outcome Measures

Primary Outcomes (3)

• Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol 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.

  0 to 5 hours and 0 to 24 hours on Day 1

• Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants

  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.

  0 to 5 hours and 0 to 24 hours on Day 8 and Day 15

• Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants

  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.

  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

Study Arms (2)

Healthy controls

OTHER

Approximately 15 healthy participants of age 18 years or above will be included in the study and will receive STM intermittently via oral route. The total duration of study for healthy participants will be approximately 2 weeks.

Other: Lactulose and Mannitol solution; Other: Sucralose

Thermal injury participants

OTHER

Approximately 25 thermally injured participants having TBSA more than or equal to 15 percent and who are co-consented to the SIFTI-2 and HESTIA studies will be included in the study and will receive STM intermittently via oral route. The total duration of study for thermal injury participants will be approximately 6 months.

Other: Lactulose and Mannitol solution; Other: Sucralose

Interventions

Lactulose and Mannitol solution OTHER

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.

Healthy controls; Thermal injury participants

Sucralose OTHER

Participants will receive 3 capsules of Sucralose (2g), a non-investigational medicinal product, by oral route to measure intestinal permeability.

Healthy controls; Thermal injury participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Birmingham, B15 2TH, United Kingdom

Location

MeSH Terms

Conditions

Burns

Interventions

Lactulose; trichlorosucrose

Condition Hierarchy (Ancestors)

Wounds and Injuries

Intervention Hierarchy (Ancestors)

Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Results Point of Contact

• Title: GSK Reponse Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 8, 2017
• Study Start: January 29, 2018
• Primary Completion: March 26, 2018
• Study Completion: March 26, 2018
• Last Updated: August 19, 2019
• Results First Posted: August 19, 2019

Record last verified: 2019-07

Locations

GB (1)