Non-alcoholic Fatty Liver Disease (NAFLD)MeSHNCT04282005
Metabolic Surgery for Steato-Hepatitis
A study testing Metabolic/Bariatric surgery and Lifestyle and Diet in people with Non-alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steato-Hepatitis (NASH), run by King's College London at 1 site in United Kingdom.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes mellitus (T2DM) and is characterised by excess liver fat on imaging or histology. NAFLD affects up to 25% of the Western population. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease (NAFLD), Non-Alcoholic Steato-Hepatitis (NASH)
- What is being tested?
- Metabolic/Bariatric surgery and Lifestyle and Diet
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 Feb 2020to 1 Jan 2022
- Phase
- Interventional
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- BMI greater than 35 kg/m2 (or >32.5. kg/m2 for patients of South Asian, Caribbean or Black ethnicities) with raised alanine transaminase (ALT), aspartate transaminase (AST) and a FibroScan® score > 7.9 (indicating presence of NAFLD and high likelihood of NASH).
Who cannot join
- other causes of liver disease such as viral, alcoholic (alcohol consumption >20 g/day for women or >30 g/day for men),
- auto-immune disease
- use of certain medications that may interfere with outcome measures (i.e. corticosteroids, insulin and glycoprotein-1 (GLP-1) analogues).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
King's College London
London
Francesco Rubino, Prof, 020 7848 5217, francesco.rubino@kcl.ac.uk
About this study
Official title: Metabolic Surgery for the Treatment and Understanding of Non-Alcoholic Steato-Hepatitis (NASH): Weight-Dependent and Weight-Independent Effects
Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes mellitus (T2DM) and is characterised by excess liver fat on imaging or histology. NAFLD affects up to 25% of the Western population. It's more aggressive form is non-alcoholic steatohepatitis (NASH) characterised by cell injury, inflammation and fibrosis, and is associated with increased mortality from liver and cardiovascular disease. Currently, there is no specific treatment for NASH. Diet and exercise-induced weight loss remain the only recommended options. However, maintaining weight loss in the long term is difficult. There is therefore a significant unmet need for effective therapy in patients with NASH that can address the underlying mechanisms of disease. Although preliminary observational evidence suggests that bariatric/metabolic surgery, especially RYGB can improve NASH, no controlled trials to date has confirmed the efficacy of surgery compared to standard weight loss programs. Also, while animal and clinical studies have shown that bariatric surgery exerts weight-independent effects on glucose metabolism, it is yet unknown if the observed effects of bariatric/metabolic surgery on NASH are due to weight loss alone or result from additional, weight-independent mechanisms, like in the case of T2DM. If the effect of surgery on inflammation, liver fibrosis and other mechanisms of cardiometabolic risk were found to be independent on weight reduction, there would be profound and far-reaching implications for both the treatment and the understanding of NASH, cardiovascular disease and obesity-related cancers.
This project will investigate the hypothesis that, similarly to surgical control of diabetes, bariatric/metabolic surgery can also exert weight-independent effects on mechanisms of disease in NAFLD/NASH (i.e. influence on lowgrade inflammation and markers of fibrosis)
Read the detailed description
This study's population includes patients with severe obesity (BMI >35kg/m2 or >32.5. kg/m2 if patient of South Asian, Caribbean or Black ethnicity) and non-alcoholic fatty liver disease (NAFLD) who are eligible for bariatric/metabolic surgery and are on the waiting list for either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at King's College Hospital. Patients who meet study criteria will be assigned to the study groups as described below:
- Surgery Group: Fourteen patients who meet study criteria will be assigned to the study group and will undergo surgery; 7 RYGB and 7 SG, as planned for their standard care.
- Lifestyle Intervention Group: Fourteen patients matched to the surgery group for age, gender, BMI, diabetes status, and NAFLD score will undergo additional lifestyle interventions, dietary counselling (either a meal replacement diet or a low calorie diet) by a dietician aimed at inducing at least a 5-7% weight reduction, prior to their surgery (while on the waiting list for surgery).
Each participant in both the surgery and lifestyle intervention group will then attend the baseline visit.
At the baseline visit the participant will undergo a metabolic lab panel from bloods already provided to the clinic. This visit will also involve the clinical team performing an ultrasound-guided fine needle aspiration (FNA) of the liver. The fine needle aspiration will involve inserting a small needle through the skin to take a small sample of cells from the liver. It will be carried out in the Institute of Liver Studies at King's College Hospital. The clinical research team will also access the participants medical record to collect data from your medical history including weight, height, body mass index (BMI) and previous FibroScan®. Additionally, a saliva swab, urine and stool sample will be collected.
A subgroup of patients (6 participants in the Lifestyle Intervention Group, 6 undergoing RYGB, 6 undergoing SG) will undergo a mixed meal test (MMT) to investigate changes in meal-response of circulating cardiometabolic markers, bile acids and gut hormone as well as calculated insulin sensitivity/secretion. The surgery group patients will undergo surgery as per standard practice and will be reviewed in the bariatric clinic 4-6 weeks' post surgery- this will be at 5-7% weight loss (WL). At the 5-7% WL visit the patient will undergo a metabolic lab panel, a liver FNA, will have their weight and height recorded and BMI calculated. A new FibroScan will be performed.
Additionally, a saliva swab, urine and stool sample will be collected. The 12 patients ( 6 RYGB, 6 SG) in the surgery group who were included in the previous MMT will undergo a second MMT to investigate the change in meal-response of circulating cardio-metabolic markers, bile acids, gut hormones, insulin sensitivity/secretion post-surgery.
The lifestyle intervention group participants will attend a one-to-one dietary consultation with a registered dietician to select a diet plan: either a low-calorie diet or meal replacement diet to induce 5-7% WL. Information booklets that will aid dieting will be provided to the participant. The participant will then be expected to follow the dietary advice in order to achieve a 5-7% WL. The clinical research team will provide additional phone call consultations at 2-, 4-, 8-, 12-, 14-, 16-, 18-, 20-, 22-, 24-weeks post-lifestyle intervention to assess weight change, diet adherence and motivation. Once the participant has a 5-7% WL they will attend the bariatric clinic for their 5-7% WL visit. At the 5-7% WL visit the patient will undergo a metabolic lab panel, a liver FNA, will have their weight and height recorded and BMI calculated. A new FibroScan will be performed. Additionally, a saliva swab, urine and stool sample will be collected. The 6 patients in the lifestyle intervention group who were included in the previous MMT will undergo a second MMT to investigate the change in meal-response of circulating cardio-metabolic markers, bile acids, gut hormones, insulin sensitivity/secretion post-lifestyle intervention.
The outcome measures above will be measured at two time-points; baseline and after 5-7% weight loss in both groups. The study design allows to control for weight loss (through an equivalent weight loss of 5-7% between the two groups) and to understand the effects bariatric/metabolic surgery versus lifestyle intervention (diet and exercise), by mechanisms independent of weight-loss, on markers of NASH and cardiovascular risk, therefore allowing to identify weight-independent effects of bariatric/metabolic surgery, if they exist. Based on published data it is predicted that it will take 3-6 months for patients to achieve 5-7% weight loss (WL) from the lifestyle intervention used in this study and 4-6 weeks after surgery.
Adipose and liver tissue from intraoperative biopsies and gastric and intestinal tissue from surgical waste will be collected and stored for future ethically approved research.
- Being tested
- Metabolic/Bariatric surgery, Lifestyle and Diet
- Keywords
- Metabolic Surgery, Bariatric Surgery, NASH, Diabetes, Obesity
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metabolic/Bariatric surgeryProcedure or surgery
Patients will undergo surgery; 7 RYGB and 7 SG, as planned for their standard care.
Lifestyle and DietOther
Patients will be provided with a lifestyle interventions including dietary counselling choosing between a Low-Calorie Diet or a Meal Replacement Diet.
| Study group | Role | What they receive |
|---|---|---|
| surgery group | Experimental | Fourteen patients who meet study criteria will be assigned to the study group and will undergo surgery; 7 RYGB and 7 SG, as planned for their standard care. Receives: Procedure: Metabolic/Bariatric surgery |
| lifestyle and diet | Active comparator | Fourteen patients matched to the surgery group for age, gender, BMI, diabetes status, and NALFD score will undergo additional lifestyle interventions, dietary counselling and or meal replacement by a dietician aimed at inducing at least a 5-7% weight reduction, prior to their surgery (while on the waiting list for surgery). Receives: Other: Lifestyle and Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of liver inflammation and fibrosis
Markers of liver injury in blood [i.e. CK-18, tissue inhibitor of metalloproteinases (TIMP-1) amino-terminal pro-peptide of type III collagen (PIIINP), hyaluronic acid].
Measured: Change from baseline to 4-6 weeks (for the surgery group) and to 6 months (lifestyle intervention group)
Assessment of liver inflammation and fibrosis
Serum adipokines [i.e. adiponectin, visfatin, IL-6, TNFa].
Measured: Change from baseline to 4-6 weeks (for the surgery group) and to 6 months (lifestyle intervention group)
Assessment of liver inflammation and fibrosis
FibroScan® score
Measured: Change from baseline to 4-6 weeks (for the surgery group) and to 6 months (lifestyle intervention group)
Assessment of liver inflammation and fibrosis
Fine Needle Aspiration of the liver to obtain a measurement of inflammatory cells in liver
Measured: Change from baseline to 4-6 weeks (for the surgery group) and to 6 months (lifestyle intervention group)
Secondary outcomes (4)
Assessment of markers of cardiovascular disease in fasting and postprandial phase in response to a mixed meal test (MMT) in a subset of patients (total no.=18; 6 RYGB, 6 SG, 6 lifestyle intervention)
Serum levels of apoprotein (apolipoproteins; apoprotein C3, apoprotein C2, and apoprotein E). Blood will be obtained at 0, 30 and 60 minutes.
- Bile acids: Blood will be obtained at 0, 30 and 60 minutes. Adipose and liver tissue from intraoperative biopsies; gastric and intestinal tissue from surgical waste will be collected. Furthermore, urine, saliva and stool will be obtained at baseline and at 5-7% WL to be stored for use in future downstream hypothesis.
Measured: Changes from 0 to 30 and 60 minutes after meal consumption.
Assessment of gut hormones in fasting and postprandial phase in response to a mixed meal test (MMT) in a subset of patients (total no.=18; 6 RYGB, 6 SG, 6 lifestyle intervention)
Plasma levels gut hormones [i.e.GLP-1, PYY3-36, ghrelin, glucose, insulin, c-peptide levels] will be measured.
Measured: Changes from -10 minutes to 0, 15, 30, 60, 90, 120 and 180 minutes after meal consumption.
Assessment of insulin sensitivity in fasting and postprandial phase in response to a mixed meal test (MMT) in a subset of patients (total no.=18; 6 RYGB, 6 SG, 6 lifestyle intervention)
Oral glucose insulin sensitivity (OGIS) index will be used to calculate insulin sensitivity.
Measured: Changes from -10 minutes to 0, 15, 30, 60, 90, 120 and 180 minutes after meal consumption.
Assessment of bile acids in fasting and postprandial phase in response to a mixed meal test (MMT) in a subset of patients (total no.=18; 6 RYGB, 6 SG, 6 lifestyle intervention)
Measurement of bile acids in blood.
Measured: Changes from 0 to 30 and 60 minutes after meal consumption.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2020
- Study start13 Feb 2020
- Primary completion30 Mar 2021 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Non-alcoholic Fatty Liver Disease (NAFLD)Studies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study's population includes patients with severe obesity and non-alcoholic fatty liver disease who are eligible for bariatric surgery and are on the waiting list for either Roux en Y gastric bypass or sleeve gastrectomy at King's College Hospital. Main outcome measures will include several markers of inflammation and liver fibrosis assessed in plasma samples and Fine Needle Aspiration of the liver. Secondary outcome measures will include novel markers of cardiovascular risk, bile acids as well as standard markers of metabolic disease.
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04282005
- Sponsor's protocol ID
- 267076
- Acronym
- MeSH
- Status last verified
- Sep 2019
- First submitted
- 20 Sep 2019
- Last updated
- 5 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015 Jun 9;313(22):2263-73. doi: 10.1001/jama.2015.5370.
PubMed 26057287Rubino F, Nathan DM, Eckel RH, Schauer PR, Alberti KG, Zimmet PZ, Del Prato S, Ji L, Sadikot SM, Herman WH, Amiel SA, Kaplan LM, Taroncher-Oldenburg G, Cummings DE; Delegates of the 2nd Diabetes Surgery Summit. Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations. Diabetes Care. 2016 Jun;39(6):861-77. doi: 10.2337/dc16-0236.
PubMed 27222544Jennings A, Hughes CA, Kumaravel B, Bachmann MO, Steel N, Capehorn M, Cheema K. Evaluation of a multidisciplinary Tier 3 weight management service for adults with morbid obesity, or obesity and comorbidities, based in primary care. Clin Obes. 2014 Oct;4(5):254-66. doi: 10.1111/cob.12066. Epub 2014 Jul 1.
PubMed 25825858Pembroke T, Gallimore A, Godkin A. Tracking the kinetics of intrahepatic immune responses by repeated fine needle aspiration of the liver. J Immunol Methods. 2015 Sep;424:131-5. doi: 10.1016/j.jim.2015.04.011. Epub 2015 Apr 22.
PubMed 25914090Pechlaner R, Tsimikas S, Yin X, Willeit P, Baig F, Santer P, Oberhollenzer F, Egger G, Witztum JL, Alexander VJ, Willeit J, Kiechl S, Mayr M. Very-Low-Density Lipoprotein-Associated Apolipoproteins Predict Cardiovascular Events and Are Lowered by Inhibition of APOC-III. J Am Coll Cardiol. 2017 Feb 21;69(7):789-800. doi: 10.1016/j.jacc.2016.11.065.
PubMed 28209220Halperin F, Ding SA, Simonson DC, Panosian J, Goebel-Fabbri A, Wewalka M, Hamdy O, Abrahamson M, Clancy K, Foster K, Lautz D, Vernon A, Goldfine AB. Roux-en-Y gastric bypass surgery or lifestyle with intensive medical management in patients with type 2 diabetes: feasibility and 1-year results of a randomized clinical trial. JAMA Surg. 2014 Jul;149(7):716-26. doi: 10.1001/jamasurg.2014.514.
PubMed 24899464Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, Raverdy V, Leteurtre E, Dharancy S, Louvet A, Romon M, Duhamel A, Pattou F, Mathurin P. Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients. Gastroenterology. 2015 Aug;149(2):379-88; quiz e15-6. doi: 10.1053/j.gastro.2015.04.014. Epub 2015 Apr 25.
PubMed 25917783
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Surgery for the Treatment and Understanding of Non-Alcoholic Steato-Hepatitis (NASH): Weight-Dependent and Weight-Independent Effects
- ClinicalTrials.gov ID
- NCT04282005
- Acronym / sponsor ID
- MeSH / 267076
- Keywords
- Metabolic Surgery, Bariatric Surgery, NASH, Diabetes, Obesity
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Study start
- 13 Feb 2020 (actual)
- Primary completion
- 30 Mar 2021 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 24 Feb 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.
Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes mellitus (T2DM) and is characterised by excess liver fat on imaging or histology. NAFLD affects up to 25% of the Western population. It's more aggressive form is non-alcoholic steatohepatitis (NASH) characterised by cell injury, inflammation and fibrosis, and is associated with increased mortality from liver and cardiovascular disease. Currently, there is no specific treatment for NASH. Diet and exercise-induced weight loss remain the only recommended options. However, maintaining weight loss in the long term is difficult. There is therefore a significant unmet need for effective therapy in patients with NASH that can address the underlying mechanisms of disease. Although preliminary observational evidence suggests that bariatric/metabolic surgery, especially RYGB can improve NASH, no controlled trials to date has confirmed the efficacy of surgery compared to standard weight loss programs. Also, while animal and clinical studies have shown that bariatric surgery exerts weight-independent effects on glucose metabolism, it is yet unknown if the observed effects of bariatric/metabolic surgery on NASH are due to weight loss alone or result from additional, weight-independent mechanisms, like in the case of T2DM. If the effect of surgery on inflammation, liver fibrosis and other mechanisms of cardiometabolic risk were found to be independent on weight reduction, there would be profound and far-reaching implications for both the treatment and the understanding of NASH, cardiovascular disease and obesity-related cancers.
This project will investigate the hypothesis that, similarly to surgical control of diabetes, bariatric/metabolic surgery can also exert weight-independent effects on mechanisms of disease in NAFLD/NASH (i.e. influence on lowgrade inflammation and markers of fibrosis)
Detailed description
This study's population includes patients with severe obesity (BMI >35kg/m2 or >32.5. kg/m2 if patient of South Asian, Caribbean or Black ethnicity) and non-alcoholic fatty liver disease (NAFLD) who are eligible for bariatric/metabolic surgery and are on the waiting list for either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at King's College Hospital. Patients who meet study criteria will be assigned to the study groups as described below:
- Surgery Group: Fourteen patients who meet study criteria will be assigned to the study group and will undergo surgery; 7 RYGB and 7 SG, as planned for their standard care.
- Lifestyle Intervention Group: Fourteen patients matched to the surgery group for age, gender, BMI, diabetes status, and NAFLD score will undergo additional lifestyle interventions, dietary counselling (either a meal replacement diet or a low calorie diet) by a dietician aimed at inducing at least a 5-7% weight reduction, prior to their surgery (while on the waiting list for surgery).
Each participant in both the surgery and lifestyle intervention group will then attend the baseline visit.
At the baseline visit the participant will undergo a metabolic lab panel from bloods already provided to the clinic. This visit will also involve the clinical team performing an ultrasound-guided fine needle aspiration (FNA) of the liver. The fine needle aspiration will involve inserting a small needle through the skin to take a small sample of cells from the liver. It will be carried out in the Institute of Liver Studies at King's College Hospital. The clinical research team will also access the participants medical record to collect data from your medical history including weight, height, body mass index (BMI) and previous FibroScan®. Additionally, a saliva swab, urine and stool sample will be collected.
A subgroup of patients (6 participants in the Lifestyle Intervention Group, 6 undergoing RYGB, 6 undergoing SG) will undergo a mixed meal test (MMT) to investigate changes in meal-response of circulating cardiometabolic markers, bile acids and gut hormone as well as calculated insulin sensitivity/secretion. The surgery group patients will undergo surgery as per standard practice and will be reviewed in the bariatric clinic 4-6 weeks' post surgery- this will be at 5-7% weight loss (WL). At the 5-7% WL visit the patient will undergo a metabolic lab panel, a liver FNA, will have their weight and height recorded and BMI calculated. A new FibroScan will be performed.
Additionally, a saliva swab, urine and stool sample will be collected. The 12 patients ( 6 RYGB, 6 SG) in the surgery group who were included in the previous MMT will undergo a second MMT to investigate the change in meal-response of circulating cardio-metabolic markers, bile acids, gut hormones, insulin sensitivity/secretion post-surgery.
The lifestyle intervention group participants will attend a one-to-one dietary consultation with a registered dietician to select a diet plan: either a low-calorie diet or meal replacement diet to induce 5-7% WL. Information booklets that will aid dieting will be provided to the participant. The participant will then be expected to follow the dietary advice in order to achieve a 5-7% WL. The clinical research team will provide additional phone call consultations at 2-, 4-, 8-, 12-, 14-, 16-, 18-, 20-, 22-, 24-weeks post-lifestyle intervention to assess weight change, diet adherence and motivation. Once the participant has a 5-7% WL they will attend the bariatric clinic for their 5-7% WL visit. At the 5-7% WL visit the patient will undergo a metabolic lab panel, a liver FNA, will have their weight and height recorded and BMI calculated. A new FibroScan will be performed. Additionally, a saliva swab, urine and stool sample will be collected. The 6 patients in the lifestyle intervention group who were included in the previous MMT will undergo a second MMT to investigate the change in meal-response of circulating cardio-metabolic markers, bile acids, gut hormones, insulin sensitivity/secretion post-lifestyle intervention.
The outcome measures above will be measured at two time-points; baseline and after 5-7% weight loss in both groups. The study design allows to control for weight loss (through an equivalent weight loss of 5-7% between the two groups) and to understand the effects bariatric/metabolic surgery versus lifestyle intervention (diet and exercise), by mechanisms independent of weight-loss, on markers of NASH and cardiovascular risk, therefore allowing to identify weight-independent effects of bariatric/metabolic surgery, if they exist. Based on published data it is predicted that it will take 3-6 months for patients to achieve 5-7% weight loss (WL) from the lifestyle intervention used in this study and 4-6 weeks after surgery.
Adipose and liver tissue from intraoperative biopsies and gastric and intestinal tissue from surgical waste will be collected and stored for future ethically approved research.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This study's population includes patients with severe obesity and non-alcoholic fatty liver disease who are eligible for bariatric surgery and are on the waiting list for either Roux en Y gastric bypass or sleeve gastrectomy at King's College Hospital. Main outcome measures will include several markers of inflammation and liver fibrosis assessed in plasma samples and Fine Needle Aspiration of the liver. Secondary outcome measures will include novel markers of cardiovascular risk, bile acids as well as standard markers of metabolic disease.
| Arm | Type | Receives |
|---|---|---|
| surgery group | Experimental | Procedure: Metabolic/Bariatric surgeryFourteen patients who meet study criteria will be assigned to the study group and will undergo surgery; 7 RYGB and 7 SG, as planned for their standard care. |
| lifestyle and diet | Active comparator | Other: Lifestyle and DietFourteen patients matched to the surgery group for age, gender, BMI, diabetes status, and NALFD score will undergo additional lifestyle interventions, dietary counselling and or meal replacement by a dietician aimed at inducing at least a 5-7% weight reduction, prior to their surgery (while on the waiting list for surgery). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- BMI greater than 35 kg/m2 (or >32.5. kg/m2 for patients of South Asian, Caribbean or Black ethnicities) with raised alanine transaminase (ALT), aspartate transaminase (AST) and a FibroScan® score > 7.9 (indicating presence of NAFLD and high likelihood of NASH).
Key exclusion criteria (3 listed)
- other causes of liver disease such as viral, alcoholic (alcohol consumption >20 g/day for women or >30 g/day for men),
- auto-immune disease
- use of certain medications that may interfere with outcome measures (i.e. corticosteroids, insulin and glycoprotein-1 (GLP-1) analogues).
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 |
|---|---|---|
| Metabolic/Bariatric surgeryPatients will undergo surgery; 7 RYGB and 7 SG, as planned for their standard care. | Procedure or surgery | surgery group |
| Lifestyle and DietPatients will be provided with a lifestyle interventions including dietary counselling choosing between a Low-Calorie Diet or a Meal Replacement Diet. | Other | lifestyle and diet |
Primary outcome
Assessment of liver inflammation and fibrosis
Time frame: Change from baseline to 4-6 weeks (for the surgery group) and to 6 months (lifestyle intervention group)
Markers of liver injury in blood [i.e. CK-18, tissue inhibitor of metalloproteinases (TIMP-1) amino-terminal pro-peptide of type III collagen (PIIINP), hyaluronic acid].
Assessment of liver inflammation and fibrosis
Time frame: Change from baseline to 4-6 weeks (for the surgery group) and to 6 months (lifestyle intervention group)
Serum adipokines [i.e. adiponectin, visfatin, IL-6, TNFa].
Assessment of liver inflammation and fibrosis
Time frame: Change from baseline to 4-6 weeks (for the surgery group) and to 6 months (lifestyle intervention group)
FibroScan® score
Assessment of liver inflammation and fibrosis
Time frame: Change from baseline to 4-6 weeks (for the surgery group) and to 6 months (lifestyle intervention group)
Fine Needle Aspiration of the liver to obtain a measurement of inflammatory cells in liver
4 secondary outcomes
Assessment of markers of cardiovascular disease in fasting and postprandial phase in response to a mixed meal test (MMT) in a subset of patients (total no.=18; 6 RYGB, 6 SG, 6 lifestyle intervention)
Time frame: Changes from 0 to 30 and 60 minutes after meal consumption.
Assessment of gut hormones in fasting and postprandial phase in response to a mixed meal test (MMT) in a subset of patients (total no.=18; 6 RYGB, 6 SG, 6 lifestyle intervention)
Time frame: Changes from -10 minutes to 0, 15, 30, 60, 90, 120 and 180 minutes after meal consumption.
Assessment of insulin sensitivity in fasting and postprandial phase in response to a mixed meal test (MMT) in a subset of patients (total no.=18; 6 RYGB, 6 SG, 6 lifestyle intervention)
Time frame: Changes from -10 minutes to 0, 15, 30, 60, 90, 120 and 180 minutes after meal consumption.
Assessment of bile acids in fasting and postprandial phase in response to a mixed meal test (MMT) in a subset of patients (total no.=18; 6 RYGB, 6 SG, 6 lifestyle intervention)
Time frame: Changes from 0 to 30 and 60 minutes after meal consumption.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2020.
- Background: PubMed 26057287Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015 Jun 9;313(22):2263-73. doi: 10.1001/jama.2015.5370.
- Background: PubMed 27222544Rubino F, Nathan DM, Eckel RH, Schauer PR, Alberti KG, Zimmet PZ, Del Prato S, Ji L, Sadikot SM, Herman WH, Amiel SA, Kaplan LM, Taroncher-Oldenburg G, Cummings DE; Delegates of the 2nd Diabetes Surgery Summit. Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations. Diabetes Care. 2016 Jun;39(6):861-77. doi: 10.2337/dc16-0236.
- Background: PubMed 25825858Jennings A, Hughes CA, Kumaravel B, Bachmann MO, Steel N, Capehorn M, Cheema K. Evaluation of a multidisciplinary Tier 3 weight management service for adults with morbid obesity, or obesity and comorbidities, based in primary care. Clin Obes. 2014 Oct;4(5):254-66. doi: 10.1111/cob.12066. Epub 2014 Jul 1.
- Background: PubMed 25914090Pembroke T, Gallimore A, Godkin A. Tracking the kinetics of intrahepatic immune responses by repeated fine needle aspiration of the liver. J Immunol Methods. 2015 Sep;424:131-5. doi: 10.1016/j.jim.2015.04.011. Epub 2015 Apr 22.
- Background: PubMed 28209220Pechlaner R, Tsimikas S, Yin X, Willeit P, Baig F, Santer P, Oberhollenzer F, Egger G, Witztum JL, Alexander VJ, Willeit J, Kiechl S, Mayr M. Very-Low-Density Lipoprotein-Associated Apolipoproteins Predict Cardiovascular Events and Are Lowered by Inhibition of APOC-III. J Am Coll Cardiol. 2017 Feb 21;69(7):789-800. doi: 10.1016/j.jacc.2016.11.065.
- Background: PubMed 24899464Halperin F, Ding SA, Simonson DC, Panosian J, Goebel-Fabbri A, Wewalka M, Hamdy O, Abrahamson M, Clancy K, Foster K, Lautz D, Vernon A, Goldfine AB. Roux-en-Y gastric bypass surgery or lifestyle with intensive medical management in patients with type 2 diabetes: feasibility and 1-year results of a randomized clinical trial. JAMA Surg. 2014 Jul;149(7):716-26. doi: 10.1001/jamasurg.2014.514.
- Background: PubMed 25917783Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, Raverdy V, Leteurtre E, Dharancy S, Louvet A, Romon M, Duhamel A, Pattou F, Mathurin P. Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients. Gastroenterology. 2015 Aug;149(2):379-88; quiz e15-6. doi: 10.1053/j.gastro.2015.04.014. Epub 2015 Apr 25.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metabolic/Bariatric surgery and Lifestyle and Diet in people with Non-alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steato-Hepatitis (NASH), run by King's College London 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 1 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 5 Mar 2020. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rubino Francesco, MD (020 7848 5217, francesco.rubino@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of liver inflammation and fibrosis (time frame: Change from baseline to 4-6 weeks (for the surgery group) and to 6 months (lifestyle intervention group)). The study lists 4 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 NCT04282005, which also lists 7 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 5 Mar 2020.