NCT03242434

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

Terminated Phase 1 Results posted Last updated 19 August 2019

What this trial tests

Phase 1 trial testing Lactulose and Mannitol solution in Burns in 18 participants. Terminated before completion.

Timeline

29 January 2018

Primary endpoint
26 March 2018

26 March 2018

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	18
Start date	29 January 2018
Primary completion	26 March 2018
Estimated completion	26 March 2018
Sites	1 location across United Kingdom

Drugs / interventions tested

• Lactulose and Mannitol solution
• Sucralose — full drug profile →

Conditions studied

• Burns — all drugs for Burns →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Burns. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol on Day 1 Primary · 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.

Day 1, 0 to 5 hours

Group	Value	95% CI
Healthy Participants	0.0078	± 0.00102
Thermally Injured Participants	0.0415	± 0.06243

Day 1, 0 to 24 hours

Group	Value	95% CI
Healthy Participants	0.0093	± 0.00409
Thermally Injured Participants	0.0296	± 0.04031

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

Day 8 (0-5 hours)

Group	Value	95% CI
Healthy Participants	0.0132	± 0.020600

Day 15 (0-5 hours)

Group	Value	95% CI
Healthy Participants	0.0016	± 0.00548

Day 8 (0-24 hours)

Group	Value	95% CI
Healthy Participants	0.0092	± 0.01304

Day 15 (0-24 hours)

Group	Value	95% CI
Healthy Participants	0.0090	± 0.00698

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

Day 3, (0-5 hours), n= 3

Group	Value	95% CI
Thermally Injured Participants	-0.0037	± 0.09936

Day 5, (0-5 hours), n= 3

Group	Value	95% CI
Thermally Injured Participants	-0.0213	± 0.08213

Day 7, (0-5 hours), n= 2

Group	Value	95% CI
Thermally Injured Participants	0.0566	± 0.07509

Day 11, (0-5 hours), n= 1

Group	Value	95% CI
Thermally Injured Participants	-0.1044	± NA

Day 13, (0-5 hours), n= 1

Group	Value	95% CI
Thermally Injured Participants	-0.0043	± NA

Day 3, (0-24 hours), n= 3

Group	Value	95% CI
Thermally Injured Participants	0.0111	± 0.09085

Day 5, (0-24 hours), n= 3

Group	Value	95% CI
Thermally Injured Participants	-0.0046	± 0.06456

Day 7, (0-24 hours), n= 2

Group	Value	95% CI
Thermally Injured Participants	0.0178	± 0.02640

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious adverse events (SAE) and Non-SAE were collected from Day 1 up to 6 months for thermal injury participants and SAE and Non-SAE were collected from Day 1 up to Day 15 for healthy participants. Safety Population comprised of all participants who received at least one dose of STM and have at least one post-dose safety assessment.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Healthy Participants

Serious: 0/15 (0%)

Deaths: 0/15

Thermally Injured Participants

Serious: 0/3 (0%)

Deaths: 2/3

Other adverse events (3 terms — click to expand)

Reaction	System	Healthy Participants	Thermally Injured Particip…
Abdominal distension	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Headache	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT03242434 adverse events section.

Sponsor's own description

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).

Publications & conference data

No peer-reviewed publications indexed yet for this trial.