Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04820036 |
| Other study ID # |
2020P003540 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 6, 2021 |
| Est. completion date |
July 2024 |
Study information
| Verified date |
November 2023 |
| Source |
Brigham and Women's Hospital |
| Contact |
Michele B Ryan, MS |
| Phone |
617-525-8266 |
| Email |
mryan[@]bwh.harvard.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide.
Affecting approximately one-third of the United States (U.S.) population, the prevalence of
NAFLD increases to 90% in patients with obesity. In 25% of patients, NAFLD progresses to a
more severe form-non-alcoholic steatohepatitis (NASH)-which further increases the risks of
cirrhosis and hepatocellular carcinoma. In 2017, the lifetime costs of caring for NASH
patients in the U.S. were estimated at $222.6 billion, with the cost of caring for the
advanced NASH (fibrosis stage ≥ 3) being $95.4 billion. It is projected that the number of
NASH cases will increase by 63% from 2015 to 2030. Given the weight loss efficacy of
Endoscopic Bariatric and Metabolic Therapies (EBMTs), it has been suggested that EBMTs may
serve as a novel treatment category for NASH. Previously, the PI and Co-Is studied the effect
of Intragastric balloons (IGB)-the oldest EBMT device-on NASH. EUS liver biopsy performed at
the time of IGB removal revealed resolution of all NASH histologic features including
fibrosis. A follow-up study by a different group showed similar findings. Furthermore,
studies have showed the benefits of S-ESG and Aspiration Therapy (AT) on non-histologic
features of NASH. Given the greater weight loss experienced after P-ESG compared to IGB (20%
vs 10% TWL) and the more reproducible technique and shorter learning curve of the current
P-ESG compared to S-ESG, we aim to assess the effect of P-ESG on NASH.
Description:
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide.
Affecting approximately one-third of the United States (U.S.) population, the prevalence of
NAFLD increases to 90% in patients with obesity. In 25% of patients, NAFLD progresses to a
more severe form-non-alcoholic steatohepatitis (NASH)-which further increases the risks of
cirrhosis and hepatocellular carcinoma. In 2017, the lifetime costs of caring for NASH
patients in the U.S. were estimated at $222.6 billion, with the cost of caring for the
advanced NASH (fibrosis stage ≥ 3) being $95.4 billion. It is projected that the number of
NASH cases will increase by 63% from 2015 to 2030.
Liver biopsy (LB) remains the gold standard for diagnosing NASH. Although the presence of
fibrosis is not required for diagnosis, fibrosis stage is the strongest predictor of
liver-related outcomes, with stages 3 and 4 being associated with a mortality relative risk
of 6.7 and 11.1, respectively, compared to no fibrosis. Traditionally, LB has been performed
via a percutaneous or transjugular approach. With advancements in endoscopic ultrasound (EUS)
technologies, EUS-guided LB (EUS-LB) has emerged as an alternative means, with a 90%-100%
diagnostic yield and 0-0.9% adverse event (AE) rate.
In patients with advanced fibrosis, the main determinant of decompensation and mortality is
the presence of portal hypertension (PH), defined as hepatic venous portal gradient (HVPG) >
5 mmHg. In 2017, Dr. Guadalupe Garcia-Tsao (Co-I) further subcategorized compensated
cirrhosis into those with no PH (HVPG ≤ 5 mmHg), mild PH (HVPG > 5 but < 10 mmHg) and
clinically significant PH (HVPG ≥ 10 mmHg) given the differences in their pathophysiological
mechanisms, prognosis and potentially therapeutic approach.
Traditionally, HVPG is obtained by subtracting the free hepatic venous pressure (FHVP) from
the wedged hepatic venous pressure (WHVP), which is used as a surrogate of portal venous
pressure (PVP). In 2016, Dr. Marvin Ryou (Co-I) reported the safety and technical feasibility
of measuring true PVP and HVP and thus directly assess portal pressure gradient (PPG) in pigs
using a digital pressure wire delivered through an EUS-based needle. Since then, the
technology has progressed with the current device consisting of an EUS-based needle connected
to a digital compact manometer. Studies in humans now report 92%-100% technical success
without AEs (compared to 7-9% AE rate for traditional LB).
The mainstay of treatment for NASH remains weight loss achieved via lifestyle modification
(LM). Previous studies show a correlation between weight loss and improvement in histologic
features of NASH with approximately 10% total weight loss (TWL) required for fibrosis
regression. Nevertheless, the average weight loss associated with LM is 3.8%, with less than
10% of patients able to achieve the 10% TWL threshold, leaving the majority of NASH patients
undertreated.
Endoscopic bariatric and metabolic therapy (EBMT) is an emerging field for the treatment of
obesity. To date, four EBMT devices/procedures are approved by the Food and Drug
Administration (FDA) and available: intragastric balloon (IGB), endoscopic sleeve
gastroplasty via suturing (S-ESG), endoscopic sleeve gastroplasty via plication (P-ESG), also
known as POSE, and aspiration therapy (AT).
P-ESG involves the use of an endoscopic plication device to reduce gastric volume. While
P-ESG has been available in the U.S. for almost a decade, in 2017, Dr. Christopher Thompson
(Co-I) invented a new plication pattern. Specifically, instead of placing plications
primarily in the fundus, a novel P-ESG procedure, also known as distal POSE, involves placing
plications in the gastric body, sparing the fundus. In addition to assisting with the first
new P-ESG case in 2017, the PI, along with Dr. Thompson, has continued to refine the
techniques to optimize efficiency, efficacy and generalizability. With the current technique,
P-ESG appears reproducible and associated with a shorter learning curve compared to S-ESG.
Furthermore, our study estimated a mean of 15% TWL, with all patients achieving ≥ 10% TWL
without AEs at 6 months and a mean of 20% TWL at 12 months (see Preliminary Data).
Given the weight loss efficacy of EBMTs, it has been suggested that EBMTs may serve as a
novel treatment category for NASH. Previously, the PI and Co-Is studied the effect of IGB-the
oldest EBMT device-on NASH. EUS-LB performed at the time of IGB removal revealed resolution
of all NASH histologic features including fibrosis. A follow-up study by a different group
showed similar findings. Furthermore, studies have showed the benefits of S-ESG and AT on
non-histologic features of NASH. Given the greater weight loss experienced after P-ESG
compared to IGB (20% vs 10% TWL) and the more reproducible technique and shorter learning
curve of the current P-ESG compared to S-ESG, we aim to assess the effect of P-ESG on NASH.
