Effect of DMR in the Treatment of NASH

NCT03536650 | Completed

• 1 other identifier: P2017/302
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

NASH - Nonalcoholic Steatohepatitis

Keywords

Metabolic diseases

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (12)

• Change in Magnetic Resonance Fat Fraction (MRFF) from baseline in the following 6 months in DMR subjects.

  baseline and 6 months post-procedure

• Change in NAS score from baseline in the following 12 months in DMR subjects.

  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

  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

  baseline and 12 months post-procedure

• Change in Transient Elastography using Firboscan from baseline in the following at 6 months in DMR subjects

  baseline and 6 months post-procedure

Study Arms (1)

DMR procedure

EXPERIMENTAL

Device: DMR

Interventions

DMR DEVICE

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

Also known as: Revita

DMR procedure

Eligibility Criteria

• Age: 28 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Erasme University Hospital: lead
• Fractyl Health Inc.: collaborator

Study Sites (1)

Erasme Hospital

Brussels, 1070, Belgium

Location

Related Publications (19)

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• Chalasani 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.

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• Vernon 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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• Rajagopalan H, Cherrington AD, Thompson CC, Kaplan LM, Rubino F, Mingrone G, Becerra P, Rodriguez P, Vignolo P, Caplan J, Rodriguez L, Galvao Neto MP. Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes: 6-Month Interim Analysis From the First-in-Human Proof-of-Concept Study. Diabetes Care. 2016 Dec;39(12):2254-2261. doi: 10.2337/dc16-0383. Epub 2016 Aug 12.

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MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Metabolic Diseases

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jacques Deviere, PhD, MD

  Erasme University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: May 25, 2018
• Study Start: November 8, 2017
• Primary Completion: July 15, 2020
• Study Completion: December 31, 2020
• Last Updated: February 25, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)