Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Metabolic Surgery for Steato-Hepatitis (MeSH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04282005
Recruitment Status : Recruiting
First Posted : February 24, 2020
Last Update Posted : March 5, 2020
Sponsor:
Information provided by (Responsible Party):
King's College London

Brief 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. 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)


Condition or disease Intervention/treatment Phase
Non-alcoholic Fatty Liver Disease (NAFLD) Non-Alcoholic Steato-Hepatitis (NASH) Procedure: Metabolic/Bariatric surgery Other: Lifestyle and Diet Not Applicable

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: Metabolic Surgery for the Treatment and Understanding of Non-Alcoholic Steato-Hepatitis (NASH): Weight-Dependent and Weight-Independent Effects
Actual Study Start Date : February 13, 2020
Estimated Primary Completion Date : March 30, 2021
Estimated Study Completion Date : January 1, 2022


Arm Intervention/treatment
Experimental: 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.
Procedure: Metabolic/Bariatric surgery
Patients will undergo surgery; 7 RYGB and 7 SG, as planned for their standard care.

Active Comparator: lifestyle and diet
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).
Other: Lifestyle and Diet
Patients will be provided with a lifestyle interventions including dietary counselling choosing between a Low-Calorie Diet or a Meal Replacement Diet.




Primary Outcome Measures :
  1. 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].

  2. 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].

  3. 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

  4. 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


Secondary Outcome Measures :
  1. 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. ]

    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.


  2. 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. ]
    Plasma levels gut hormones [i.e.GLP-1, PYY3-36, ghrelin, glucose, insulin, c-peptide levels] will be measured.

  3. 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. ]
    Oral glucose insulin sensitivity (OGIS) index will be used to calculate insulin sensitivity.

  4. 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. ]
    Measurement of bile acids in blood.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

• 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).

Exclusion Criteria:

  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04282005


Contacts
Layout table for location contacts
Contact: Rubino Francesco, MD 020 7848 5217 francesco.rubino@kcl.ac.uk

Locations
Layout table for location information
United Kingdom
King's College London Recruiting
London, United Kingdom
Contact: Francesco Rubino, Prof    020 7848 5217    francesco.rubino@kcl.ac.uk   
Sponsors and Collaborators
King's College London
Publications:

Layout table for additonal information
Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT04282005    
Other Study ID Numbers: 267076
First Posted: February 24, 2020    Key Record Dates
Last Update Posted: March 5, 2020
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by King's College London:
Metabolic Surgery
Bariatric Surgery
NASH
Diabetes
Obesity
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis A
Hepatitis
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections