BurnsPhase 1NCT03242434

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

A Phase 1 study testing Lactulose and Mannitol solution and Sucralose in people with Burns, run by GlaxoSmithKline at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Burns
What is being tested?: Lactulose and Mannitol solution and Sucralose
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteUnited Kingdom
Study dates: 29 Jan 2018to 26 Mar 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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:

Show all 11Show fewer

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.

Who cannot join

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.

Show all 31Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Birmingham, B15 2TH

Other trials in United Kingdom

About this study

Official title: A Prospective, Longitudinal Study to Investigate the Effect of Thermal Injury on Intestinal Permeability and Systemic Inflammation (HESTIA)

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
Being tested: Lactulose and Mannitol solution, Sucralose
Keywords: Mannitol, Intestinal permeability, Thermal injury, HESTIA, Sucralose, Lactulose
Medical subject headings: Burns

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03242434
Study group	Role	What they receive
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. Receives: 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. Receives: Other: Lactulose and Mannitol solution; Other: Sucralose

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Jan 201826 Mar 2018

First posted8 Aug 2017
Study start29 Jan 2018
Primary completion26 Mar 2018
Study completion26 Mar 2018

Why it stopped: This trial was supporting the development of an asset which was terminated, thus the data from the study were no longer required.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for BurnsStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03242434
Sponsor's protocol ID: 206243
Status last verified: Jul 2019
First submitted: 3 Aug 2017
Last updated: 19 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Burns trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Prospective, Longitudinal Study to Investigate the Effect of Thermal Injury on Intestinal Permeability and Systemic Inflammation (HESTIA)
ClinicalTrials.gov ID: NCT03242434
Acronym / sponsor ID: 206243
Conditions: Burns
Keywords: Mannitol, Intestinal permeability, Thermal injury, HESTIA, Sucralose, Lactulose
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: This trial was supporting the development of an asset which was terminated, thus the data from the study were no longer required.
Enrolment: 18 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 29 Jan 2018 (actual)
Primary completion: 26 Mar 2018 (actual)
Study completion: 26 Mar 2018 (actual)
First posted: 8 Aug 2017 (actual)
Results: Posted 19 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Healthy controls	Other	Other: Lactulose and Mannitol solution, Other: SucraloseApproximately 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.
Thermal injury participants	Other	Other: Lactulose and Mannitol solution, Other: SucraloseApproximately 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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.
Participants must be greater than or equal to 18 years of age.

Key exclusion criteria (31 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Lactulose and Mannitol solutionParticipants 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.	Other	Healthy controls, Thermal injury participants
SucraloseParticipants will receive 3 capsules of Sucralose (2g), a non-investigational medicinal product, by oral route to measure intestinal permeability.	Other	Healthy controls, Thermal injury participants

Primary outcome

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.

Results and safety

Results posted to the registry on 19 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Healthy Participants	15	15
Thermal Injury Participants	3	1

Primary outcome: 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. Mean (Standard Deviation). Unit: Ratio

Measure	Healthy Participants n = 7	Thermally Injured Participants n = 3
Day 1, 0 to 5 hours	0.0078 (0.00102)	0.0415 (0.06243)
Day 1, 0 to 24 hours	0.0093 (0.00409)	0.0296 (0.04031)

Population analysed: 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.

Primary outcome: 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. Mean (Standard Deviation). Unit: Ratio

Measure	Healthy Participants n = 5
Day 8 (0-5 hours)	0.0132 (0.020600)
Day 15 (0-5 hours)	0.0016 (0.00548)
Day 8 (0-24 hours)	0.0092 (0.01304)
Day 15 (0-24 hours)	0.0090 (0.00698)

Population analysed: Evaluable Population. Only those participants with data available at the specified data points were analyzed.

Primary outcome: 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. Mean (Standard Deviation). Unit: Ratio

Measure	Thermally Injured Participants n = 3
Day 3, (0-5 hours), n= 3	-0.0037 (0.09936)
Day 5, (0-5 hours), n= 3	-0.0213 (0.08213)
Day 7, (0-5 hours), n= 2	0.0566 (0.07509)
Day 11, (0-5 hours), n= 1	-0.1044 (NA)
Day 13, (0-5 hours), n= 1	-0.0043 (NA)
Day 3, (0-24 hours), n= 3	0.0111 (0.09085)
Day 5, (0-24 hours), n= 3	-0.0046 (0.06456)
Day 7, (0-24 hours), n= 2	0.0178 (0.02640)

Population analysed: Evaluable Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Adverse events

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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Healthy Participants	0 of 15 (0%)	5 of 15 (33.3%)	0 of 15
Thermally Injured Participants	0 of 3 (0%)	0 of 3 (0%)	2 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lactulose and Mannitol solution and Sucralose in people with Burns, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03242434.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2019.