Alcoholic HepatitisCREEDNCT04544020
Changes in gUt micRobiota After Enteral Feeding (in Alcoholic Hepatitis)
An observational study of Alcoholic Hepatitis, run by University of Aberdeen at 1 site in United Kingdom.
Trial summary
Drinking large amount of alcohol can cause damage to the liver. If the liver is severely injured by alcohol it can become very inflamed and this condition is called alcoholic hepatitis. Alcoholic hepatitis can be life threatening. There is no cure for alcoholic hepatitis. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Alcoholic Hepatitis
- What is being tested?
- NG feeding
- How many people
- 6 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2019to 21 Apr 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: - adults admitted to hospital. Diagnosis of alcoholic hepatitis. Expected to receive nasogastric feeding for at least 3 days.
Who may be able to join
- Adults patients: age 16 and above
- Diagnosis of alcoholic hepatitis confirmed by treating hepatologists and defined as:
- Bilirubin >80 umol/l
- Documented history of continuing alcohol harmful use
- ALT< 500 umol/L
- Clinical decision to start NG feeding and prospect to continue NG feeding >3 days
Who cannot join
- Age <16
- Hepatocellular carcinoma
- Pregnancy and breastfeeding
- Inability to provide informed consent
- Any reasons in the opinion of the investigator which can compromise participation in the trial or affect patient health
Trial locations and contacts
1 site in 1 country.
About this study
Drinking large amount of alcohol can cause damage to the liver. If the liver is severely injured by alcohol it can become very inflamed and this condition is called alcoholic hepatitis. Alcoholic hepatitis can be life threatening. There is no cure for alcoholic hepatitis. It is known that stop drinking and have good nutrition can help the liver to recover.
Infections are very common for people who suffer from alcoholic hepatitis. Sometimes these infection can be very severe. It is not always possible to find out where the infection is coming from. But the bacteria living in the bowel may move to other organs causing these infections and an illness like alcoholic hepatitis can cause "bad bacteria" to take over from "good bacteria" in the gut.
Read more
This study wants to understand the changes in the bacteria in the bowel of people who have an acute inflammation of the liver cause by alcohol (alcoholic hepatitis).
The investigators will take stool samples from patients admitted in the hospital with alcoholic hepatitis. The investigators will run tests on the stools that can find out which bacteria live in the bowel. Its is expected to find these bacteria to be different from the ones living in the bowel of healthy people. The investigators are interested to see if these bacteria change once the patients are given good nutrition using a small tube from the nose to the stomach. This type of nutrition is used routinely to help improve the liver in severe alcoholic hepatitis. The investigators will take some more stool sample from these patients after the nutrition through the tube has started to check how the bacteria change with nutrition.
Better tools to check the bacteria in the bowel are now available so this can help the investigators to understand better if changing bacteria in the bowel can help recovery in alcoholic hepatitis.
Read the detailed description
Subjects admitted to hospital with a diagnosis of alcoholic hepatitis and who are planned to receive nasogastric feeding for at least 7 days will be eligible for the study.
A stool sample will be collected prior to commence enteral nutrition via nasogastric tube and analysed. Subsequently further stool samples will be collected and analysed at day 3 and day 7 after commencing nasogastric feeding.
DNA will be extracted from each of the samples, and bacterial 16S rRNA genes will be PCR amplified and sent for sequencing at the CGEBM using an Illumina MiSeq machine. This will generate at least 2 million paired end reads (2 x 300 bp), which will be assembled and analysed using the Mothur software platform.The investigators will also analyse the short chain fatty acids profiles within the stool samples using gas chromatography. Shannon Diversity Index will be used to assess the bacterial diversity and Pielou's index will be used to assess species evenness at each time point. Comparison between time points will be performed. Microbiota composition at the different time points will be assessed using Mothur software to detect if there are systematic changes to specific members of the gut microbiota during enteral feeding. Prevalence by different molecular methodologies will be assessed and the results from study patients will be compared with their baseline samples by Fisher's exact test.
Missing data will be handled using a missing indicator.
Subjects will be approached by the team in charge of the clinical care and option to enter the study will be offered. Information leaflet will be provided to the subject 24h before consenting and possibility to discuss with trial team.
Data will be collected by authorised members of trial team in a fit for purpose ad hoc password protected excel data base as eCRF. Source data will be electronic patient file or paper case notes. Source data of microbiome analysis will be computer report. Accuracy of data entry will be checked by a separate delegated member of the team. External monitoring occurs at a regular basis for clinical trial arrange by sponsor.
Patient confidentiality will be maintained at all time. No identifiable data will be collected. eCRF will be password protected and stored in encrypted hospital computer protected by password. consent or other paper documentation will be kept separate in locked cabinets within the premises of the hospital.
Adverse Events reporting will be performed by a competent and delegated member of staff, according to our sponsor standard operating procedure and recorded.
- Conditions
- Alcoholic Hepatitis
- Being tested
- NG feeding
- Keywords
- gut microbiome, NG feeding
- Medical subject headings
- Hepatitis, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NG feedingDietary supplement
NG feeding
| Study group | Role | What they receive |
|---|---|---|
| subjects | subjects with alcoholic hepatitis receiving NG feeding Receives: Dietary Supplement: NG feeding |
What is being measured
The primary outcome is the main question the study is designed to answer.
alteration of bacterial microbiome diversity and evenness following enteral feeding in alcoholic hepatitis
To understand how the gut microbiome changes in patients with AH following enteral feeding.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2020
- Study start1 Sep 2019
- Primary completion21 Apr 2023
- Study completion21 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aberdeen
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Grampian
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04544020
- Sponsor's protocol ID
- 2019GA002
- Acronym
- CREED
- Status last verified
- May 2023
- First submitted
- 2 Sep 2020
- Last updated
- 22 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: we will plan to share all patient IPD, protocol including analysis plan
Publications
Moreno C, Deltenre P, Senterre C, Louvet A, Gustot T, Bastens B, Hittelet A, Piquet MA, Laleman W, Orlent H, Lasser L, Serste T, Starkel P, De Koninck X, Negrin Dastis S, Delwaide J, Colle I, de Galocsy C, Francque S, Langlet P, Putzeys V, Reynaert H, Degre D, Trepo E. Intensive Enteral Nutrition Is Ineffective for Patients With Severe Alcoholic Hepatitis Treated With Corticosteroids. Gastroenterology. 2016 Apr;150(4):903-10.e8. doi: 10.1053/j.gastro.2015.12.038. Epub 2016 Jan 5.
PubMed 26764182Dubinkina VB, Tyakht AV, Odintsova VY, Yarygin KS, Kovarsky BA, Pavlenko AV, Ischenko DS, Popenko AS, Alexeev DG, Taraskina AY, Nasyrova RF, Krupitsky EM, Shalikiani NV, Bakulin IG, Shcherbakov PL, Skorodumova LO, Larin AK, Kostryukova ES, Abdulkhakov RA, Abdulkhakov SR, Malanin SY, Ismagilova RK, Grigoryeva TV, Ilina EN, Govorun VM. Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease. Microbiome. 2017 Oct 17;5(1):141. doi: 10.1186/s40168-017-0359-2.
PubMed 29041989Puri P, Thursz M. Intensive Enteral Nutrition in Alcoholic Hepatitis: More Food for Thought. Gastroenterology. 2016 Apr;150(4):803-5. doi: 10.1053/j.gastro.2016.02.061. Epub 2016 Feb 26. No abstract available.
PubMed 26924095
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in gUt micRobiota After Enteral Feeding (in Alcoholic Hepatitis)
- ClinicalTrials.gov ID
- NCT04544020
- Acronym / sponsor ID
- CREED / 2019GA002
- Conditions
- Alcoholic Hepatitis
- Keywords
- gut microbiome, NG feeding
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of AberdeenUniversity, hospital or other
- Collaborators
- NHS Grampian
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 21 Apr 2023 (actual)
- Study completion
- 21 Apr 2023 (actual)
- First posted
- 10 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Drinking large amount of alcohol can cause damage to the liver. If the liver is severely injured by alcohol it can become very inflamed and this condition is called alcoholic hepatitis. Alcoholic hepatitis can be life threatening. There is no cure for alcoholic hepatitis. It is known that stop drinking and have good nutrition can help the liver to recover.
Infections are very common for people who suffer from alcoholic hepatitis. Sometimes these infection can be very severe. It is not always possible to find out where the infection is coming from. But the bacteria living in the bowel may move to other organs causing these infections and an illness like alcoholic hepatitis can cause "bad bacteria" to take over from "good bacteria" in the gut.
This study wants to understand the changes in the bacteria in the bowel of people who have an acute inflammation of the liver cause by alcohol (alcoholic hepatitis).
The investigators will take stool samples from patients admitted in the hospital with alcoholic hepatitis. The investigators will run tests on the stools that can find out which bacteria live in the bowel. Its is expected to find these bacteria to be different from the ones living in the bowel of healthy people. The investigators are interested to see if these bacteria change once the patients are given good nutrition using a small tube from the nose to the stomach. This type of nutrition is used routinely to help improve the liver in severe alcoholic hepatitis. The investigators will take some more stool sample from these patients after the nutrition through the tube has started to check how the bacteria change with nutrition.
Better tools to check the bacteria in the bowel are now available so this can help the investigators to understand better if changing bacteria in the bowel can help recovery in alcoholic hepatitis.
Detailed description
Subjects admitted to hospital with a diagnosis of alcoholic hepatitis and who are planned to receive nasogastric feeding for at least 7 days will be eligible for the study.
A stool sample will be collected prior to commence enteral nutrition via nasogastric tube and analysed. Subsequently further stool samples will be collected and analysed at day 3 and day 7 after commencing nasogastric feeding.
DNA will be extracted from each of the samples, and bacterial 16S rRNA genes will be PCR amplified and sent for sequencing at the CGEBM using an Illumina MiSeq machine. This will generate at least 2 million paired end reads (2 x 300 bp), which will be assembled and analysed using the Mothur software platform.The investigators will also analyse the short chain fatty acids profiles within the stool samples using gas chromatography. Shannon Diversity Index will be used to assess the bacterial diversity and Pielou's index will be used to assess species evenness at each time point. Comparison between time points will be performed. Microbiota composition at the different time points will be assessed using Mothur software to detect if there are systematic changes to specific members of the gut microbiota during enteral feeding. Prevalence by different molecular methodologies will be assessed and the results from study patients will be compared with their baseline samples by Fisher's exact test.
Missing data will be handled using a missing indicator.
Subjects will be approached by the team in charge of the clinical care and option to enter the study will be offered. Information leaflet will be provided to the subject 24h before consenting and possibility to discuss with trial team.
Data will be collected by authorised members of trial team in a fit for purpose ad hoc password protected excel data base as eCRF. Source data will be electronic patient file or paper case notes. Source data of microbiome analysis will be computer report. Accuracy of data entry will be checked by a separate delegated member of the team. External monitoring occurs at a regular basis for clinical trial arrange by sponsor.
Patient confidentiality will be maintained at all time. No identifiable data will be collected. eCRF will be password protected and stored in encrypted hospital computer protected by password. consent or other paper documentation will be kept separate in locked cabinets within the premises of the hospital.
Adverse Events reporting will be performed by a competent and delegated member of staff, according to our sponsor standard operating procedure and recorded.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| subjects | – | Dietary Supplement: NG feedingsubjects with alcoholic hepatitis receiving NG feeding |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- - adults admitted to hospital. Diagnosis of alcoholic hepatitis. Expected to receive nasogastric feeding for at least 3 days.
Key inclusion criteria (6 listed)
- Adults patients: age 16 and above
- Diagnosis of alcoholic hepatitis confirmed by treating hepatologists and defined as:
- Bilirubin >80 umol/l
- Documented history of continuing alcohol harmful use
- ALT< 500 umol/L
Key exclusion criteria (5 listed)
- Age <16
- Hepatocellular carcinoma
- Pregnancy and breastfeeding
- Inability to provide informed consent
- Any reasons in the opinion of the investigator which can compromise participation in the trial or affect patient health
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 |
|---|---|---|
| NG feedingNG feeding | Dietary supplement | subjects |
Primary outcome
alteration of bacterial microbiome diversity and evenness following enteral feeding in alcoholic hepatitis
Time frame: 7 days
To understand how the gut microbiome changes in patients with AH following enteral feeding.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2023.
- Background: PubMed 26764182Moreno C, Deltenre P, Senterre C, Louvet A, Gustot T, Bastens B, Hittelet A, Piquet MA, Laleman W, Orlent H, Lasser L, Serste T, Starkel P, De Koninck X, Negrin Dastis S, Delwaide J, Colle I, de Galocsy C, Francque S, Langlet P, Putzeys V, Reynaert H, Degre D, Trepo E. Intensive Enteral Nutrition Is Ineffective for Patients With Severe Alcoholic Hepatitis Treated With Corticosteroids. Gastroenterology. 2016 Apr;150(4):903-10.e8. doi: 10.1053/j.gastro.2015.12.038. Epub 2016 Jan 5.
- Background: PubMed 29041989Dubinkina VB, Tyakht AV, Odintsova VY, Yarygin KS, Kovarsky BA, Pavlenko AV, Ischenko DS, Popenko AS, Alexeev DG, Taraskina AY, Nasyrova RF, Krupitsky EM, Shalikiani NV, Bakulin IG, Shcherbakov PL, Skorodumova LO, Larin AK, Kostryukova ES, Abdulkhakov RA, Abdulkhakov SR, Malanin SY, Ismagilova RK, Grigoryeva TV, Ilina EN, Govorun VM. Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease. Microbiome. 2017 Oct 17;5(1):141. doi: 10.1186/s40168-017-0359-2.
- Background: PubMed 26924095Puri P, Thursz M. Intensive Enteral Nutrition in Alcoholic Hepatitis: More Food for Thought. Gastroenterology. 2016 Apr;150(4):803-5. doi: 10.1053/j.gastro.2016.02.061. Epub 2016 Feb 26. No abstract available.
- Individual participant dataSharing planned: Undecided. we will plan to share all patient IPD, protocol including analysis plan
Related trials for Alcoholic Hepatitis
Active, not recruitingPhase 1/2
A Study to Evaluate ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease or With Metabolic Dysfunction-Associated Steatohepatitis (MASLD/MASH)
Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis
RecruitingPhase 2
Study to Evaluate ALN-CIDEB in Adults With Fibrotic Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Metabolic Dysfunction-Associated Steatohepatitis (MASH)
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
RecruitingPhase 3
Study to Evaluate the Safety and Efficacy of Larsucosterol in Participants With Alcohol-associated Hepatitis (AH)
Hepatitis
RecruitingObservational study
Blood Collection Biorepository for Liver Disease Research
Non-Alcoholic Steatohepatitis(NASH), Hepatitis C
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alcoholic Hepatitis, run by University of Aberdeen 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 6 inclusion and 5 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: finished, as of the sponsor's last update on 22 May 2023. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
alteration of bacterial microbiome diversity and evenness following enteral feeding in alcoholic hepatitis (time frame: 7 days). 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 NCT04544020, which also lists 3 linked publications.
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 22 May 2023.