Diabetes Prevention Program for the Treatment of Nonalcoholic Fatty Liver Disease

Pilot Study: Diabetes Prevention Program for the Treatment of Nonalcoholic Fatty Liver Disease

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.

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Fatty Liver Disease
• Intervention / Treatment: Behavioral: Diabetes Prevention Program

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10003
      • Mount Sinai Union Square

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Patients enrolled in 1 year program	Behavioral: Diabetes Prevention Program; The Diabetes Prevention Program is a 1 year validated program to prevent the development of type 2 diabetes. Participants with NAFLD will engage will work with a CDC certified DPP certified lifestyle coach and other participants in a group setting during the study focusing on lifestyle changes to achieve weight loss and improvement in NAFLD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants in the program at the end of the study	Retention defined as number of patients in the program at the end of the study	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Weight	Change in Weight at 12 months as compared to baseline	baseline and 12 months
Hepatic steatosis via Fibroscan	Changes in hepatic steatosis measured with fibroscan using the controlled attenuated parameter.	Baseline
Hepatic steatosis via Fibroscan	Changes in hepatic steatosis measured with fibroscan using the controlled attenuated parameter .	6 months
Hepatic steatosis via Fibroscan	Changes in hepatic steatosis measured with fibroscan using the controlled attenuated parameter.	12 months
Glycosylated A1C	Glycosylated A1C in assessing metabolic comorbidity	Baseline
Glycosylated A1C	Glycosylated A1C in assessing metabolic comorbidity	6 months
Glycosylated A1C	Glycosylated A1C in assessing metabolic comorbidity	12 months
Lipid levels	Lipid levels in assessing metabolic comorbidity	Baseline
Lipid levels	Lipid levels in assessing metabolic comorbidity	6 months
Lipid levels	Lipid levels in assessing metabolic comorbidity	12 months
Liver enzymes levels	Liver enzymes levels for ALT, AST, and ALP	Baseline
Liver enzymes levels	Liver enzymes levels for ALT, AST, and ALP	6 months
Liver enzymes levels	Liver enzymes levels for ALT, AST, and ALP	12 months
Bilirubin level	Liver enzyme level for Bilirubin	Baseline
Bilirubin level	Liver enzyme level for Bilirubin	6 months
Bilirubin level	Liver enzyme level for Bilirubin	12 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Amreen Dinani, Icahn School of Medicine, Division of Liver Diseases

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2018
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): October 31, 2019

Study Registration Dates

• First Submitted: July 28, 2021
• First Submitted That Met QC Criteria: July 28, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: July 28, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: GCO 18-1283

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: was not including inn protocol and consent form

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No