Trial Outcomes & Findings for Investigation of Thermal Injury on Intestinal Permeability in Both Thermal Injury and Healthy Participants (NCT NCT03242434)
NCT ID: NCT03242434
Last Updated: 2019-08-19
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
0 to 5 hours and 0 to 24 hours on Day 1
Results posted on
2019-08-19
Participant Flow
This study was a longitudinal study which involved healthy participants and participants who had sustained a thermal injury. The study was conducted in United Kingdom. This study was terminated early prior to the full sample size being achieved as the development of the formulation was terminated.
A total 23 participants were screened for study of which 5 participants were screen failure and 18 participants were enrolled in the study.
Participant milestones
| Measure |
Healthy Participants
Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram \[g\]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.
|
Thermal Injury Participants
Participants were invited to undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
3
|
|
Overall Study
COMPLETED
|
15
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Healthy Participants
Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram \[g\]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.
|
Thermal Injury Participants
Participants were invited to undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.
|
|---|---|---|
|
Overall Study
Death
|
0
|
2
|
Baseline Characteristics
Investigation of Thermal Injury on Intestinal Permeability in Both Thermal Injury and Healthy Participants
Baseline characteristics by cohort
| Measure |
Healthy Participants
n=14 Participants
Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram \[g\]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.
|
Thermally Injured Participants
n=3 Participants
Participants were invited to undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.4 Years
STANDARD_DEVIATION 9.43 • n=5 Participants
|
52.0 Years
STANDARD_DEVIATION 21.00 • n=7 Participants
|
43.3 Years
STANDARD_DEVIATION 12.02 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Central/South Asian Heritage
|
1 Count of Participants
n=5 Participants
|
0 Count of Participants
n=7 Participants
|
1 Count of Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
13 Count of Participants
n=5 Participants
|
2 Count of Participants
n=7 Participants
|
15 Count of Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Count of Participants
n=5 Participants
|
0 Count of Participants
n=7 Participants
|
1 Count of Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0 to 5 hours and 0 to 24 hours on Day 1Population: Evaluable Population included of all participants in the safety population excluding any healthy volunteers that received any concomitant medication or food and drink containing Sugar Test Material (STM) as identified by review of the protocol deviation. Only those participants with data available at the specified data points were analyzed.
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.
Outcome measures
| Measure |
Healthy Participants
n=7 Participants
Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram \[g\]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.
|
Thermally Injured Participants
n=3 Participants
Participants were invited undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.
|
|---|---|---|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol on Day 1
Day 1, 0 to 5 hours
|
0.0078 Ratio
Standard Deviation 0.00102
|
0.0415 Ratio
Standard Deviation 0.06243
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol on Day 1
Day 1, 0 to 24 hours
|
0.0093 Ratio
Standard Deviation 0.00409
|
0.0296 Ratio
Standard Deviation 0.04031
|
PRIMARY outcome
Timeframe: 0 to 5 hours and 0 to 24 hours on Day 8 and Day 15Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed.
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.
Outcome measures
| Measure |
Healthy Participants
n=5 Participants
Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram \[g\]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.
|
Thermally Injured Participants
Participants were invited undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.
|
|---|---|---|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants
Day 8 (0-5 hours)
|
0.0132 Ratio
Standard Deviation 0.020600
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants
Day 15 (0-5 hours)
|
0.0016 Ratio
Standard Deviation 0.00548
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants
Day 8 (0-24 hours)
|
0.0092 Ratio
Standard Deviation 0.01304
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Healthy Participants
Day 15 (0-24 hours)
|
0.0090 Ratio
Standard Deviation 0.00698
|
—
|
PRIMARY outcome
Timeframe: 0 to 5 hours on Days 3, 5, 7, 11, 13 and 0 to 24 hours on Days 3, 5, 7, 9, 11 and 13Population: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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.
Outcome measures
| Measure |
Healthy Participants
n=3 Participants
Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram \[g\]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.
|
Thermally Injured Participants
Participants were invited undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.
|
|---|---|---|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 3, (0-5 hours), n= 3
|
-0.0037 Ratio
Standard Deviation 0.09936
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 5, (0-5 hours), n= 3
|
-0.0213 Ratio
Standard Deviation 0.08213
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 7, (0-5 hours), n= 2
|
0.0566 Ratio
Standard Deviation 0.07509
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 11, (0-5 hours), n= 1
|
-0.1044 Ratio
Standard Deviation NA
NA indicates data was not available as standard deviation could not be calculated for one participant.
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 13, (0-5 hours), n= 1
|
-0.0043 Ratio
Standard Deviation NA
NA indicates data was not available as standard deviation could not be calculated for one participant.
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 3, (0-24 hours), n= 3
|
0.0111 Ratio
Standard Deviation 0.09085
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 5, (0-24 hours), n= 3
|
-0.0046 Ratio
Standard Deviation 0.06456
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 7, (0-24 hours), n= 2
|
0.0178 Ratio
Standard Deviation 0.02640
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 9, (0-24 hours), n= 2
|
-0.0327 Ratio
Standard Deviation 0.05953
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 11, (0-24 hours), n= 2
|
-0.0218 Ratio
Standard Deviation 0.05846
|
—
|
|
Change From 0 to 5 Hours, and 0 to 24 Hours in the Ratio of Lactulose/Mannitol Over Time for Thermal Injury Participants
Day 13, (0-24 hours), n= 1
|
-0.0634 Ratio
Standard Deviation NA
NA indicates data was not available as standard deviation could not be calculated for one participant.
|
—
|
Adverse Events
Healthy Participants
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Thermally Injured Participants
Serious events: 0 serious events
Other events: 0 other events
Deaths: 2 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Healthy Participants
n=15 participants at risk
Healthy participants were invited to donate a blood sample for biomarker measurement on day one. They were also requested to undergo measurements of intestinal permeability by taking a 100 milliliter (mL) solution of lactulose (5 gram \[g\]) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1, 8 and 15 followed by a 24 hour urine collection.
|
Thermally Injured Participants
n=3 participants at risk
Participants were invited to undergo measurements of intestinal permeability by taking a 100 mL solution of lactulose (5 g) and mannitol (2g) along with 3 capsules (2g) of sucralose on days 1,3,5,7,9,11 and 13.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
26.7%
4/15 • Number of events 4 • 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.
Death is typically associated with the disease under study and were not reported as SAEs but instead were recorded drug related events (DREs). In thermally injured participants DREs are common and can be serious/life threatening: Deterioration of condition; Death (may be expected in burns of a large surface area); Prolongation of hospital stay; Persistent or significant disability or incapacity.
|
0.00%
0/3 • 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.
Death is typically associated with the disease under study and were not reported as SAEs but instead were recorded drug related events (DREs). In thermally injured participants DREs are common and can be serious/life threatening: Deterioration of condition; Death (may be expected in burns of a large surface area); Prolongation of hospital stay; Persistent or significant disability or incapacity.
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
1/15 • Number of events 1 • 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.
Death is typically associated with the disease under study and were not reported as SAEs but instead were recorded drug related events (DREs). In thermally injured participants DREs are common and can be serious/life threatening: Deterioration of condition; Death (may be expected in burns of a large surface area); Prolongation of hospital stay; Persistent or significant disability or incapacity.
|
0.00%
0/3 • 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.
Death is typically associated with the disease under study and were not reported as SAEs but instead were recorded drug related events (DREs). In thermally injured participants DREs are common and can be serious/life threatening: Deterioration of condition; Death (may be expected in burns of a large surface area); Prolongation of hospital stay; Persistent or significant disability or incapacity.
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1 • 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.
Death is typically associated with the disease under study and were not reported as SAEs but instead were recorded drug related events (DREs). In thermally injured participants DREs are common and can be serious/life threatening: Deterioration of condition; Death (may be expected in burns of a large surface area); Prolongation of hospital stay; Persistent or significant disability or incapacity.
|
0.00%
0/3 • 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.
Death is typically associated with the disease under study and were not reported as SAEs but instead were recorded drug related events (DREs). In thermally injured participants DREs are common and can be serious/life threatening: Deterioration of condition; Death (may be expected in burns of a large surface area); Prolongation of hospital stay; Persistent or significant disability or incapacity.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER