Principal investigator left the institution and study was never funded

The ENLIGHTEN study that will evaluate the efficacy of a novel DTx lifestyle intervention in participants with non-cirrhotic MASH. People who have MASH, the progressive subtype of MASLD, have the highest risk for liver disease progression and poor outcomes, including cirrhosis and hepatocellular carcinoma, and greater overall mortality. Thus, these participants are expected to experience the greatest benefit from treatment.

This is a randomized, controlled trial comparing DTx lifestyle intervention in participants with non-cirrhotic MASH to standard clinical care. The study includes a screening period (up to 2 wks.) followed by randomization, 52-wk treatment period and 12-wk follow-up period (total duration up to 64 wks.).

Inclusion Criteria:

1. Age 18-75 years at the time of signing informed consent

2. MASH defined by any of the following within 12-months prior to SV (V1):

   1. Liver biopsy with definitive MASH with NAS >4 with >1 in each component (i.e., steatosis, lobular inflammation, ballooning) or;
   2. Imaging study (e.g., ultrasound) with hepatic steatosis and one of the following:

   i) FIB-4 >1.3 or; ii) ELF test >7.7 or; iii) VCTE measured liver stiffness >8kPa or FAST score >0.35 or; iv) MRE measured liver stiffness >2.55kPa or MAST score >0.165

3. Possession of a smartphone (iPhone6s or newer with iOS version 15.6 or above; Android device with Android version 6 or above)

4. If participants are on GLP1-RA or other regulatory agency approved anti-obesity medication (e.g., orlistat, buproprion/naltrexone, phentermine-topiramate, phentermine, loreaserin), the medication dose must be stable (no change in dose) for the 3 mos. before SV.

5. Stable body weight for 3 mos. before screening visit defined as <5% weight loss or weight gain

Exclusion Criteria:

1. Recent (within 3 mos. of SV) participation in lifestyle intervention program or use of supplements marked for weight loss or appetite.
2. Plans to undergo bariatric surgery or initiate anti-obesity medication.
3. History of cirrhosis and/or hepatic decompensation (e.g., ascites, encephalopathy, variceal bleeding)
4. Liver disease of other etiologies (e.g., viral hepatitis), including liver transplantation
5. History of excessive alcohol consumption defined by self-report (men >30g/d or women >20g/d), AUDIT-C >4 or PETH > 20ug/L
6. History of malignancy within last 5 yrs., excluding successful treatment of non-melanoma skin cancer
7. Participant in any clinical trial or use of drugs under investigation for treatment of MASH within 3 mos. of SV
8. History of type 1 diabetes or uncontrolled type 2 diabetes (A1c >9.5% or changes in diabetes medication doses within 3 mos. of SV)
9. Recent (within 3 mos. of SV) initiation or change in dose of medications used to treat MASH (e.g., vitamin E, pioglitazone)
10. Recent (within 3 mos. of SV) use of drugs associated with the development of steatotic liver disease (e.g., methotrexate, tamoxifen)
11. Known or suspected history of drug abuse within the last 2 years prior to SV at the discretion of study investigator
12. Vulnerable participants (e.g., protected adults under guardianship or committed to an institution by governmental or judicial order)
13. Participants who cannot communicate with the study investigators or use digital technology reliably
14. Severe medical comorbidities that may hinder study participation at the discretion of study investigator
15. Current pregnancy or plans to become pregnant during the study period

For this project, we anticipate data from 120 participants enrolled into the ENLIGHTEN study. There will be ten data collection points over the study duration. We will collect demographic, clinical, quality of life and outcomes information. Data will be converted to SAS and csv formats for analysis and sharing. To protect research participant personal identifying information (PII) and protected health information (PHI), all data will be de-identified prior to receipt by the repository and sharing in accordance with guidance provided for Limited Data Sets and Data Use Agreements section of NIH HIPAA Privacy Rule summary.

We agree to deposit all data into the repository as soon as possible but no later than within one year of the completion of the funded project period for the parent award or upon acceptance of the main outcome data for publication. The data shared will be archived and available on the platform for request by researchers for a minimum of 10 years after contribution. Data will be made accessible no later than the time of our associated publication or the end of the grant period (whichever comes first).

We will make the data available via the Vivli platform. Vivli is a non-profit clinical research data sharing platform that has been created to meet the needs of researchers who use and produce clinical research data worldwide. Using the Vivli platform, researchers can share or access anonymized data using a managed access process. To access anonymized individual patient-level data (IPD) arising from this project, users complete the Vivli data request form and sign the Vivli Data Use Agreement, which limits subsequent use to the terms of the approved proposal and requires that users maintain data security, and refrain from any attempts to re-identify research participants or engage in unauthorized uses of the data. Vivli will then make the data available via secure download. Researchers have a requirement to publish their findings as part of the Data Use Agreement and once the project is complete, must confirm that the original data and documents have been destroyed.