NASH - Nonalcoholic SteatohepatitisDMR_NASH_001NCT03536650
Effect of DMR in the Treatment of NASH
A study testing DMR in people with NASH - Nonalcoholic Steatohepatitis, run by Erasme University Hospital at 1 site in Belgium.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) is a frequent disease affecting up to 25% of the USA population, 2-44% in Europe and up to 42,6-69,5% in patients with type 2 diabetes. It is a disease that could progress from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic cirrhosis and hepatocarcinoma. Read more about this study
- Who is it for?
- Ages 28 to 75 years
- Conditions the study is for
- NASH - Nonalcoholic Steatohepatitis
- What is being tested?
- DMR
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteBelgium
- Study dates
- 8 Nov 2017to 31 Dec 2020
- 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 28 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult subjects (male and female), age 28 to 75 years.
- NASH histological diagnosis according to the currently accepted definition of both EASL and AASLD, requiring the combined presence of steatosis (any degree> 5%) + lobular inflammation of any degree + liver cell ballooning of any amount, on a liver biopsy performed ≤ 6 months before screening in the study and confirmed by central reading during the periode and (apendix 1)
- SAF (steatosis, activity, fibrosis) activity score of 3 or 4 (>2)
- SAF steatosis score ≥ 1
- SAF fibrosis score < 4
- No other causes of chronic liver disease and compensated liver disease.
Show all 10Show fewer
- If applicable, have a type 2 diabetes with HbA1c <10.0 %
- BMI (body mass index) ≥ 24 and ≤ 40 kg/m2.
- Willing to sign an informed consent form.
- Willing to comply with study requirements
Who cannot join
- Evidence of another cause of liver disease.
- History of sustained alcohol ingestion defined as: daily alcohol consumption > 30 g/day for males and > 20 g/day for females.
- Previous gastrointestinal surgery such as subjects who have had Billroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions.
- Known autoimmune disease, including celiac disease, or symptoms of systemic lupus eythematosus, sleroderma or other auto-immune connective tissue disorder.
- For type 2 diabetes subjects, no current use of insulin or GLP-1 analogues.
- Type 1 diabetes.
Show all 28Show fewer
- Probable insulin production failure defined as fasting C peptide serum < 1 ng/ml.
- History of acute or chronic pancreatitis.
- Active malignancy.
- Persistent anemia defined as Hb < 10 g/dl.
- Use of anticoagulation therapy which cannot be discontinued for 7 days before and 14 days after the procedure.
- Use of P2Y12 inhibitors (clopidrogel, prasugrel, ticagrelor) which cannot be discontinued for 14 days before and14 days after the procedure.
- History of coagulopathy or upper gastro-intestinal bleeding conditions likely to bleed.
- Taking corticosteroids or drugs which possibly affect gastrointestinal motility or liver.
- Unable to discontinue NSAIDs (non-steroidal anti- inflammatory drugs) during the treatment up to 4 weeks after procedure.
- Use of weight loss medications.
- Presence of liver cirrhosis (defined by histology)
- Platelet count < 120 x 109/L.
- Clinical evidence of hepatic decompensation or severe liver impairment as defined by the presence of any of the following abnormalities:
- Serum albumin < 32 g/L.
- INR> 1.3.
- Direct bilirubin> 1.3 mg/L.
- ALT or AST > 5x ULN.
- Alkaline Phosphatase > 3x ULN.
- History of esophageal varices, ascites or hepatic encephalopathy.
- Splenomegaly.
- Human immunodeficiency virus.
- Contraindications to MRI as defined below.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Duodenal Mucosal Resurfacing (DMR) for the Treatment of Non Alcoholic Steatohepatitis (NASH), a Proof of Concept Study
Non-alcoholic fatty liver disease (NAFLD) is a frequent disease affecting up to 25% of the USA population, 2-44% in Europe and up to 42,6-69,5% in patients with type 2 diabetes. It is a disease that could progress from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic cirrhosis and hepatocarcinoma. NASH is part of continuum of metabolic syndrome and constitutes a serious public health concern manifesting by premature cardiovascular disease, end stage diabetes complication and will likely become the first cause of end stage liver disease. Insuline resistance is the hallmark of NASH. Some recent studies both in animals and humans have demonstrated abnormal hypertrophy of the duodenal mucosa, changes in enteroendocrine cell density and number, endocrine hyperplasia, and alterations in gut hormone signaling highlighting the role of the upper intestine gut in glucose homeostasis and thus insulin sensitizing. Given these physiological and pathophysiological features, abrasion of duodenal mucosa was assessed both in animals and humans. The investigators reported an improvement in both glucose homeostasis and transaminases levels suggesting possibly an improvement of NASH. Until now, lifestyle medication is the only recognized efficient treatment for fatty liver disease. Unfortunately, only a minority of patients achieve a significant weight loss and lifestyle modifications. The investigators aim to study the duodenal mucosal resurfacing procedure in patients with NASH biopsy proven in a proof of concept study allowing to assess this technique as a potential treatment to NASH.
Read the detailed description
Introduction
Non-alcoholic fatty liver disease (NAFLD) is a frequent disease affecting up to 25% of the USA population, 2-44% in Europe and up to 42,6-69,5% in patients with type 2 diabetes. It is a disease that could progress from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic cirrhosis and hepatocarcinoma. NASH is part of continuum of a metabolic syndrome and constitutes a serious public health concern, manifesting by premature cardiovascular disease, end stage diabetes complication and will likely become the first cause of end stage liver disease.
Insulin resistance is the hallmark of NASH. Some recent studies both in animals and humans have demonstrated abnormal hypertrophy of the duodenal mucosa, changes in enteroendocrine cell density and number, endocrine hyperplasia, and alterations in gut hormone signaling highlighting the role of the upper intestine gut in glucose homeostasis and thus insulin sensitizing.
Given these physiological and pathophysiological features, abrasion of duodenal mucosa was assessed both in animals and humans. The investigators reported an improvement in both glucose homeostasis and transaminases levels suggesting possibly an improvement of NASH.
Until now, lifestyle medication is the only recognized efficient treatment for fatty liver disease. Unfortunately, only a minority of patients achieve a significant weight loss and lifestyle modifications.
The investigators aim to study the duodenal mucosal resurfacing procedure in patients with NASH biopsy proven in a proof of concept study allowing to assess this technique as a potential treatment to NASH.
Design of study The study is designed as a single arm, proof of concept, non-randomized, open label trial to be conducted at one investigational site. All patients with biopsy proven NASH will undergo an upper endoscopy to perform a duodenal mucosal resurfacing procedure. Evolution of liver steatosis (assessed by MRI), insulin resistance (assessed by oral glucose tolerance test), liver damage (evaluated by blood tests), liver elastography (assessed by fibroscan, fibrotest), biometric parameters will be performed pre- and post-procedure.
Primary outcome :
- Feasability and safety of duodenal mucosal resurfacing, using Revita ™ duodenal mucosal resurfacing after submucosal injection, in patients with NASH.
Secondary outcomes:
- Evolution of steatosis assessed by MRI 6 months after the procedure.
- Evolution of liver fibrosis (assessed by Fibroscan, Fibrotest, Fibrosis four score (FIB-4) and NAFLD fibrosis score) at 6 and 12 months after the procedure.
- Evolution of liver tests at 6 and 12 months after the procedure.
- Evolution of insulin resistance at 1,3,6 and 12 months after the procedure.
- Conditions
- NASH - Nonalcoholic Steatohepatitis
- Being tested
- DMR
- Keywords
- Metabolic diseases
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DMRDevice
Also called Revita
Procedure: DMR Procedure The Fractyl DMR procedure using the Revita System utilizes an over the wire endoscopic approach to ablate the duodenum. The procedure may be completed in an endoscopic suite or in an operating room depending on the facilities and support at each investigative site. All subjects are monitored and anesthetized by conscious sedation per each facility's standard protocol. A full DMR procedure is defined as 5 complete ablations or 9 axial centimeters of circumferentially ablated tissue in the duodenum. Subjects who do not receive any ablations during the DMR procedure will be followed for safety through the 4 week visit and then discontinued from the study.
Other Names:
DMR Revita
| Study group | Role | What they receive |
|---|---|---|
| DMR procedure | Experimental | Not described Receives: Device: DMR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of duodenal mucosal resurfacing characterized by the incidence of all Adverse Device Effects (ADEs), and subsequent adverse events [ Time Frame: 12 months ] in patients with NASH.
Safety will be characterized by the incidence of all Adverse Device Effects (ADEs), non-serious and serious, possibly related to or related to the procedure and/or device that are experienced by study participants.
Safety evaluations will also be performed to ensure no subsequent adverse events have occurred and to ensure any adverse events during the trial that are considered on-going are stable or have resolved. Safety will be assessed at 1 and 6 months following the intervention.
Measured: 12 months
Secondary outcomes (12)
Change in Magnetic Resonance Fat Fraction (MRFF) from baseline in the following 6 months in DMR subjects.
Magnetic Resonance Fat fraction
Measured: baseline and 6 months post-procedure
Change in NAS score from baseline in the following 12 months in DMR subjects.
Centrally scored histological improvement in NAFLD from baseline to the end of 12 months post-procedure, where improvement is defined as:
- No worsening in fibrosis; and
- A decrease in NAFLD Activity Score (NAS) of at least 2 points
Measured: baseline and 12 months post-procedure
Change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) from baseline in the following at 6 months in DMR subjects
Absolute change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) is a fibrosis marker. A score <1.45 has a negative predictive value of over 90% for advanced liver fibrosis. A score of >3.25 has a positive predictive value of 65% for advanced fibrosis with a specificity of 97%.
Measured: baseline and 6 months post-procedure
Change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) from baseline in the following at 12 months in DMR subjects
Absolute change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) is a fibrosis marker. A score <1.45 has a negative predictive value of over 90% for advanced liver fibrosis. A score of >3.25 has a positive predictive value of 65% for advanced fibrosis with a specificity of 97%.
Measured: baseline and 12 months post-procedure
Change in Transient Elastography using Firboscan from baseline in the following at 6 months in DMR subjects
Transient Elastography
Measured: baseline and 6 months post-procedure
Change in Transient Elastography using Firboscan from baseline in the following at 12 months in DMR subjects
Transient Elastography
Measured: baseline and 12 months post-procedure
Change in Magnetic Resonance Fat Fraction (MRFF) from baseline in the following 12 months in DMR subjects.
Magnetic Resonance Fat fraction
Measured: baseline and 12 months post procedure
Change in transaminases levels from baseline in the following 6 months in DMR subjects
Transaminases levels
Measured: baseline and 6 months post-procedure
Change in transaminases levels from baseline in the following 12 months in DMR subjects
Transaminases levels
Measured: baseline and 12 months post-procedure
Change in Insulin resistance measured by oral glucose tolerance test (OGTT) from baseline in the following 6 months in DMR subjects
Insulin resistance as abnormal HOMA IR
Measured: baseline and 6 months post-procedure
Change in Insulin resistance measured by oral glucose tolerance test (OGTT) from baseline in the following 12 months in DMR subjects
Insulin resistance as abnormal HOMA IR
Measured: baseline and 12 months post procedure
Change in stage of fibrosis from baseline in the following 12 months in DMR subjects
Liver histology
Measured: baseline and 12 months post-procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study start8 Nov 2017
- Primary completion15 Jul 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for NASH - Nonalcoholic SteatohepatitisStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasme University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fractyl Health Inc.
- Responsible party
- Sponsor
- Investigators
- Jacques Deviere, PhD, MD, Principal investigator, Erasme University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03536650
- Sponsor's protocol ID
- P2017/302
- Acronym
- DMR_NASH_001
- Status last verified
- Feb 2021
- First submitted
- 13 Apr 2018
- Last updated
- 25 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Li Y, Jadhav K, Zhang Y. Bile acid receptors in non-alcoholic fatty liver disease. Biochem Pharmacol. 2013 Dec 1;86(11):1517-24. doi: 10.1016/j.bcp.2013.08.015. Epub 2013 Aug 26.
PubMed 23988487Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013 Mar;58(3):593-608. doi: 10.1016/j.jhep.2012.12.005.
PubMed 23419824Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. 2010 Nov;52(5):1836-46. doi: 10.1002/hep.24001.
PubMed 21038418Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ; American Gastroenterological Association; American Association for the Study of Liver Diseases; American College of Gastroenterologyh. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012 Jun;142(7):1592-609. doi: 10.1053/j.gastro.2012.04.001. Epub 2012 May 15. No abstract available.
PubMed 22656328Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.
PubMed 21623852Boza C, Riquelme A, Ibanez L, Duarte I, Norero E, Viviani P, Soza A, Fernandez JI, Raddatz A, Guzman S, Arrese M. Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass. Obes Surg. 2005 Sep;15(8):1148-53. doi: 10.1381/0960892055002347.
PubMed 16197788Higuera-de la Tijera F, Servin-Caamano AI. Pathophysiological mechanisms involved in non-alcoholic steatohepatitis and novel potential therapeutic targets. World J Hepatol. 2015 Jun 8;7(10):1297-301. doi: 10.4254/wjh.v7.i10.1297.
PubMed 26052375Schneck AS, Anty R, Patouraux S, Bonnafous S, Rousseau D, Lebeaupin C, Bailly-Maitre B, Sans A, Tran A, Gugenheim J, Iannelli A, Gual P. Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis. Front Physiol. 2016 Aug 19;7:344. doi: 10.3389/fphys.2016.00344. eCollection 2016.
PubMed 27594839Hannah WN Jr, Harrison SA. Effect of Weight Loss, Diet, Exercise, and Bariatric Surgery on Nonalcoholic Fatty Liver Disease. Clin Liver Dis. 2016 May;20(2):339-50. doi: 10.1016/j.cld.2015.10.008. Epub 2016 Feb 17.
PubMed 27063273Klebanoff MJ, Corey KE, Chhatwal J, Kaplan LM, Chung RT, Hur C. Bariatric surgery for nonalcoholic steatohepatitis: A clinical and cost-effectiveness analysis. Hepatology. 2017 Apr;65(4):1156-1164. doi: 10.1002/hep.28958. Epub 2017 Feb 21.
PubMed 27880977Lassailly 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 25917783Ferrannini E, Mingrone G. Impact of different bariatric surgical procedures on insulin action and beta-cell function in type 2 diabetes. Diabetes Care. 2009 Mar;32(3):514-20. doi: 10.2337/dc08-1762. No abstract available.
PubMed 19246589Klein S, Fabbrini E, Patterson BW, Polonsky KS, Schiavon CA, Correa JL, Salles JE, Wajchenberg BL, Cohen R. Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes. Obesity (Silver Spring). 2012 Jun;20(6):1266-72. doi: 10.1038/oby.2011.377. Epub 2012 Jan 19.
PubMed 22262157Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004 Jan;239(1):1-11. doi: 10.1097/01.sla.0000102989.54824.fc.
PubMed 14685093Rubino F, Forgione A, Cummings DE, Vix M, Gnuli D, Mingrone G, Castagneto M, Marescaux J. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006 Nov;244(5):741-9. doi: 10.1097/01.sla.0000224726.61448.1b.
PubMed 17060767
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Duodenal Mucosal Resurfacing (DMR) for the Treatment of Non Alcoholic Steatohepatitis (NASH), a Proof of Concept Study
- ClinicalTrials.gov ID
- NCT03536650
- Acronym / sponsor ID
- DMR_NASH_001 / P2017/302
- Conditions
- NASH - Nonalcoholic Steatohepatitis
- Keywords
- Metabolic diseases
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Erasme University HospitalUniversity, hospital or other
- Collaborators
- Fractyl Health Inc.
- Study start
- 8 Nov 2017 (actual)
- Primary completion
- 15 Jul 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 25 May 2018 (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 a frequent disease affecting up to 25% of the USA population, 2-44% in Europe and up to 42,6-69,5% in patients with type 2 diabetes. It is a disease that could progress from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic cirrhosis and hepatocarcinoma. NASH is part of continuum of metabolic syndrome and constitutes a serious public health concern manifesting by premature cardiovascular disease, end stage diabetes complication and will likely become the first cause of end stage liver disease. Insuline resistance is the hallmark of NASH. Some recent studies both in animals and humans have demonstrated abnormal hypertrophy of the duodenal mucosa, changes in enteroendocrine cell density and number, endocrine hyperplasia, and alterations in gut hormone signaling highlighting the role of the upper intestine gut in glucose homeostasis and thus insulin sensitizing. Given these physiological and pathophysiological features, abrasion of duodenal mucosa was assessed both in animals and humans. The investigators reported an improvement in both glucose homeostasis and transaminases levels suggesting possibly an improvement of NASH. Until now, lifestyle medication is the only recognized efficient treatment for fatty liver disease. Unfortunately, only a minority of patients achieve a significant weight loss and lifestyle modifications. The investigators aim to study the duodenal mucosal resurfacing procedure in patients with NASH biopsy proven in a proof of concept study allowing to assess this technique as a potential treatment to NASH.
Detailed description
Introduction
Non-alcoholic fatty liver disease (NAFLD) is a frequent disease affecting up to 25% of the USA population, 2-44% in Europe and up to 42,6-69,5% in patients with type 2 diabetes. It is a disease that could progress from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic cirrhosis and hepatocarcinoma. NASH is part of continuum of a metabolic syndrome and constitutes a serious public health concern, manifesting by premature cardiovascular disease, end stage diabetes complication and will likely become the first cause of end stage liver disease.
Insulin resistance is the hallmark of NASH. Some recent studies both in animals and humans have demonstrated abnormal hypertrophy of the duodenal mucosa, changes in enteroendocrine cell density and number, endocrine hyperplasia, and alterations in gut hormone signaling highlighting the role of the upper intestine gut in glucose homeostasis and thus insulin sensitizing.
Given these physiological and pathophysiological features, abrasion of duodenal mucosa was assessed both in animals and humans. The investigators reported an improvement in both glucose homeostasis and transaminases levels suggesting possibly an improvement of NASH.
Until now, lifestyle medication is the only recognized efficient treatment for fatty liver disease. Unfortunately, only a minority of patients achieve a significant weight loss and lifestyle modifications.
The investigators aim to study the duodenal mucosal resurfacing procedure in patients with NASH biopsy proven in a proof of concept study allowing to assess this technique as a potential treatment to NASH.
Design of study The study is designed as a single arm, proof of concept, non-randomized, open label trial to be conducted at one investigational site. All patients with biopsy proven NASH will undergo an upper endoscopy to perform a duodenal mucosal resurfacing procedure. Evolution of liver steatosis (assessed by MRI), insulin resistance (assessed by oral glucose tolerance test), liver damage (evaluated by blood tests), liver elastography (assessed by fibroscan, fibrotest), biometric parameters will be performed pre- and post-procedure.
Primary outcome :
- Feasability and safety of duodenal mucosal resurfacing, using Revita ™ duodenal mucosal resurfacing after submucosal injection, in patients with NASH.
Secondary outcomes:
- Evolution of steatosis assessed by MRI 6 months after the procedure.
- Evolution of liver fibrosis (assessed by Fibroscan, Fibrotest, Fibrosis four score (FIB-4) and NAFLD fibrosis score) at 6 and 12 months after the procedure.
- Evolution of liver tests at 6 and 12 months after the procedure.
- Evolution of insulin resistance at 1,3,6 and 12 months after the procedure.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DMR procedure | Experimental | Device: DMR |
Who may qualify
- Ages
- 28 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adult subjects (male and female), age 28 to 75 years.
- NASH histological diagnosis according to the currently accepted definition of both EASL and AASLD, requiring the combined presence of steatosis (any degree> 5%) + lobular inflammation of any degree + liver cell ballooning of any amount, on a liver biopsy performed ≤ 6 months before screening in the study and confirmed by central reading during the periode and (apendix 1)
- No other causes of chronic liver disease and compensated liver disease.
- If applicable, have a type 2 diabetes with HbA1c <10.0 %
- BMI (body mass index) ≥ 24 and ≤ 40 kg/m2.
Key exclusion criteria (28 listed)
- Evidence of another cause of liver disease.
- History of sustained alcohol ingestion defined as: daily alcohol consumption > 30 g/day for males and > 20 g/day for females.
- Previous gastrointestinal surgery such as subjects who have had Billroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions.
- Known autoimmune disease, including celiac disease, or symptoms of systemic lupus eythematosus, sleroderma or other auto-immune connective tissue disorder.
- For type 2 diabetes subjects, no current use of insulin or 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 |
|---|---|---|
| DMRAlso: RevitaProcedure: DMR Procedure The Fractyl DMR procedure using the Revita System utilizes an over the wire endoscopic approach to ablate the duodenum. The procedure may be completed in an endoscopic suite or in an operating room depending on the facilities and support at each investigative site. All subjects are monitored and anesthetized by conscious sedation per each facility's standard protocol. A full DMR procedure is defined as 5 complete ablations or 9 axial centimeters of circumferentially ablated tissue in the duodenum. Subjects who do not receive any ablations during the DMR procedure will be followed for safety through the 4 week visit and then discontinued from the study. Other Names: DMR Revita | Device | DMR procedure |
Primary outcome
Safety of duodenal mucosal resurfacing characterized by the incidence of all Adverse Device Effects (ADEs), and subsequent adverse events [ Time Frame: 12 months ] in patients with NASH.
Time frame: 12 months
Safety will be characterized by the incidence of all Adverse Device Effects (ADEs), non-serious and serious, possibly related to or related to the procedure and/or device that are experienced by study participants. Safety evaluations will also be performed to ensure no subsequent adverse events have occurred and to ensure any adverse events during the trial that are considered on-going are stable or have resolved. Safety will be assessed at 1 and 6 months following the intervention.
12 secondary outcomes
Change in Magnetic Resonance Fat Fraction (MRFF) from baseline in the following 6 months in DMR subjects.
Time frame: baseline and 6 months post-procedure
Change in NAS score from baseline in the following 12 months in DMR subjects.
Time frame: baseline and 12 months post-procedure
Change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) from baseline in the following at 6 months in DMR subjects
Time frame: baseline and 6 months post-procedure
Change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) from baseline in the following at 12 months in DMR subjects
Time frame: baseline and 12 months post-procedure
Change in Transient Elastography using Firboscan from baseline in the following at 6 months in DMR subjects
Time frame: baseline and 6 months post-procedure
Change in Transient Elastography using Firboscan from baseline in the following at 12 months in DMR subjects
Time frame: baseline and 12 months post-procedure
Change in Magnetic Resonance Fat Fraction (MRFF) from baseline in the following 12 months in DMR subjects.
Time frame: baseline and 12 months post procedure
Change in transaminases levels from baseline in the following 6 months in DMR subjects
Time frame: baseline and 6 months post-procedure
Change in transaminases levels from baseline in the following 12 months in DMR subjects
Time frame: baseline and 12 months post-procedure
Change in Insulin resistance measured by oral glucose tolerance test (OGTT) from baseline in the following 6 months in DMR subjects
Time frame: baseline and 6 months post-procedure
Change in Insulin resistance measured by oral glucose tolerance test (OGTT) from baseline in the following 12 months in DMR subjects
Time frame: baseline and 12 months post procedure
Change in stage of fibrosis from baseline in the following 12 months in DMR subjects
Time frame: baseline and 12 months post-procedure
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 25 Feb 2021.
- Background: PubMed 23988487Li Y, Jadhav K, Zhang Y. Bile acid receptors in non-alcoholic fatty liver disease. Biochem Pharmacol. 2013 Dec 1;86(11):1517-24. doi: 10.1016/j.bcp.2013.08.015. Epub 2013 Aug 26.
- Background: PubMed 23419824Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013 Mar;58(3):593-608. doi: 10.1016/j.jhep.2012.12.005.
- Background: PubMed 21038418Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. 2010 Nov;52(5):1836-46. doi: 10.1002/hep.24001.
- Background: PubMed 22656328Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ; American Gastroenterological Association; American Association for the Study of Liver Diseases; American College of Gastroenterologyh. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012 Jun;142(7):1592-609. doi: 10.1053/j.gastro.2012.04.001. Epub 2012 May 15. No abstract available.
- Background: PubMed 21623852Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.
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- Background: PubMed 27594839Schneck AS, Anty R, Patouraux S, Bonnafous S, Rousseau D, Lebeaupin C, Bailly-Maitre B, Sans A, Tran A, Gugenheim J, Iannelli A, Gual P. Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis. Front Physiol. 2016 Aug 19;7:344. doi: 10.3389/fphys.2016.00344. eCollection 2016.
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- 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.
Jacques Deviere, PhD, MD principal investigator
Erasme University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DMR in people with NASH - Nonalcoholic Steatohepatitis, run by Erasme University Hospital at 1 site in Belgium.
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 10 inclusion and 28 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 25 Feb 2021. 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 Belgium. 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?
Safety of duodenal mucosal resurfacing characterized by the incidence of all Adverse Device Effects (ADEs), and subsequent adverse events [ Time Frame: 12 months ] in patients with NASH. (time frame: 12 months). 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 NCT03536650, which also lists 19 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 25 Feb 2021.