Clinical trial NCT04988204: Diabetes Prevention Program for the Treatment of Nonalcoholic Fatty Liver Disease
Official title: Pilot Study: Diabetes Prevention Program for the Treatment of Nonalcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nonalcoholic Fatty Liver Disease
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2021-08-03
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Nonalcoholic fatty liver disease (NAFLD) is a rapidly growing epidemic worldwide and is an increasingly important etiology of chronic liver disease and hepatocellular carcinoma. NAFLD affects approximately 90 million people in the United States (US) amounting to an annual cost of $100 billion yearly. It is projected to become the leading cause of liver transplantation in the US by 2030 and is associated with significant morbidity and mortality. NAFLD is a spectrum of liver diseases, ranging from simple steatosis (nonalcoholic fatty liver, NAFL) to hepatic steatosis associated with inflammation (nonalcoholic steatohepatitis, NASH), which can be associated with liver scarring (hepatic fibrosis) and cirrhosis. There are limited therapeutic options that have been shown to effectively reduce or reverse the progression of disease.

Lifestyle modification is the backbone of therapy, but difficult to achieve. A modest amount of weight loss of approximately 3% can reduce liver steatosis and a 10% weight loss can reduce the NASH and improve liver fibrosis. The American Association of the Study of Liver Diseases (AASLD) guidelines state that "a combination of a hypocaloric diet (daily reduction by 500-1000 kcal) and moderate intensity exercise is the best likelihood of sustaining weight loss over time." There are several barriers to adopting a healthy lifestyle involving both patient and physician limitations. The aim of this study is to engage patients in a lifestyle intervention program that has already been shown to be successful in achieving weight loss goals and adopting healthier lifestyle patterns.

The CDC Diabetes Prevention Program, (DPP) was a large (n=3,234) multicenter study aimed to evaluate the effect of lifestyle intervention or treatment with metformin on the incidence of type 2 diabetes (T2DM). Lifestyle intervention reduced the incidence of T2DM by 58% (95% CI, 48-66%) and metformin reduced the incidence by 31% (95% CI, 17-43%) as compared to placebo. To prevent one case of diabetes over three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. The CDC DPP program has been adapted and tested in the multiple different community and state-wide programs including the YMCA, WorkWellNYC and NYS DPP. In these real-world models, the life style intervention program has been delivered in a group-based format by DPP lifestyle coaches. These programs have been successful like that of the randomized trial and improvements were sustainable at 6 and 12 month follow up after completion of the program. The program is now available and reimbursable through Medicare (Medicare Diabetes Prevention Program).

In this pilot study, the researchers will enroll 20 patients with NAFLD in an adapted DPP program and follow study participants for 1 year. The rationale for the proposed research is to apply the DPP to NAFLD because of the close relationship with Diabetes and determine the real-world outcome of the DPP program on weight loss in patients with NAFLD. If the researchers illustrate that weight loss can be achieved and is sustainable in patients with NAFLD enrolled in lifestyle intervention programs, the researchers can develop innovative approaches to deliver such a program nationwide in a cost-effective and sustainable manner.


Eligibility criteria: Inclusion Criteria:

* diagnosis of NAFLD, defined by the presence of hepatic steatosis with vibration controlled transient elastography (VCTE) controlled attenuation parameter (CAP) measurement over 240dB/m, or liver biopsy showing macrovesicular steatosis in ≥ 5% of hepatocytes.
* patients were 18 years and older,
* fluent in English (the program could only be conducted in English by the DPP-certified coach),
* able to meet program scheduling requirements, and able to participate in physical activity.

Exclusion Criteria:

* additional causes of liver disease such as viral hepatitis, biliary obstruction, hepatocellular carcinoma, Wilson's disease, Budd Chiari Syndrome, autoimmune hepatitis, alcoholic liver disease or alcohol use (\>20g/day women, \>30g/day men),
* aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values \>300 U/L,
* using steatogenic medications (amiodarone, methotrexate, tamoxifen, and corticosteroids),
* pregnant,
* a history of liver transplantation.

Primary outcomes:
measure: Number of participants in the program at the end of the study
timeFrame: 12 months
Secondary outcomes:
measure: Change in Weight
timeFrame: baseline and 12 months
measure: Hepatic steatosis via Fibroscan
timeFrame: Baseline
measure: Hepatic steatosis via Fibroscan
timeFrame: 6 months
measure: Hepatic steatosis via Fibroscan
timeFrame: 12 months
measure: Glycosylated A1C
timeFrame: Baseline
measure: Glycosylated A1C
timeFrame: 6 months
measure: Glycosylated A1C
timeFrame: 12 months
measure: Lipid levels
timeFrame: Baseline
measure: Lipid levels
timeFrame: 6 months
measure: Lipid levels
timeFrame: 12 months
measure: Liver enzymes levels
timeFrame: Baseline
measure: Liver enzymes levels
timeFrame: 6 months
measure: Liver enzymes levels
timeFrame: 12 months
measure: Bilirubin level
timeFrame: Baseline
measure: Bilirubin level
timeFrame: 6 months
measure: Bilirubin level
timeFrame: 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Union Square
state: New York
Study officials:
affiliation: Icahn School of Medicine, Division of Liver Diseases
name: Amreen Dinani
role: PRINCIPAL_INVESTIGATOR
References: