Clinical Outcomes From Enhanced SCREENing Strategies for Advanced NASH in Type 2 Diabetes (SCREEN NASH T2D)

Study Overview
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Brief Summary
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The study is stratified cluster randomized trial (Phase 1) and prospective cohort study and NASH registry (Phase 2). The study population will include adults with T2D and presumed advanced NASH.

Detailed Description
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The study is a multi-centered, stratified cluster randomized controlled, open-labeled two-phase study. Clusters will be independent LMC clinic sites with patients as participants. The use of the stratified cluster randomization design will help prevent the potential for cross-contamination of screening methods. Study participants who meet eligibility criteria undergo NASH screening. Everything, other than routineness of screening, is maintained the same in both the groups. The screening intervention received is determined by the site of the participant's provider. All participants enrolled will undergo biochemical screening. Regardless of randomization, any participants meeting biochemical cut-offs (FIB-4 index ≥1.3 or NFS >-1.455) will undergo FibroScans. Clinical data and a health-related quality of life assessment will also be collected.

Official Title
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A Cluster Randomized Trial to Determine Diagnostic and Clinical Outcomes From Enhanced SCREENing Strategies for Advanced NASH in Type 2 Diabetes (SCREEN NASH T2D)

Conditions
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Nonalcoholic Steatohepatitis, Type 2 Diabetes

Intervention / Treatment
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* Other: routine screening
* Other: physician-driven screening


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of T2D Age 18 - 80 years BMI >25 kg/m2 or waist circumference ≥102 cm in men and ≥88 cm in women Informed consent Exclusion Criteria: Known history of biopsy-proven NAFLD or NASH, hepatitis B, hepatitis C, HIV, liver cirrhosis, hemochromatosis, drug-induced hepatitis, alcohol-related or autoimmune hepatic disease, history of hepatic decompensation, solid organ transplant, or primary liver cancer, based on electronic medical record History of alcohol abuse (≥30 g/day or ≥3 drinks/day for males and ≥20 g/day or ≥2 drinks/day for females) Unstable patients with T2D (e.g. end stage renal disease on dialysis, late stage cancer, acute cardiovascular event or any hospitalization in the past 3 months). Note - Emergency room visit without hospitalization is not exclusionary Pregnancy/lactation Presence of implanted electronic medical device (i.e., pacemaker, as FibroScan cannot be performed) Language barriers (i.e. inability to read the consent form translated in any of the multiple languages)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: routine screening group<br>consists of 4 clusters randomized into Group 1 (includes different clinic sites from Group 2) | Other: routine screening<br>* routine screening for advanced NASH<br>|
| Active Comparator: physician-driven screening group<br>consists of 4 clusters randomized into Group 2 (includes different clinic sites from Group 1) | Other: physician-driven screening<br>* physician-driven screening for advanced NASH<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of presumed advanced NASH based on biochemical and FibroScan results | Percent of participants identified with presumed advanced NASH. Specific details for calculating the primary outcome of this study are blinded for health care providers, and therefore not disclosed in this description. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of study participants with presumed high grade fibrosis | Proportion of study participants with presumed any NASH (fibrosis-4 index >2.67 or NAFLD fibrosis score >0.675 AND FibroScan LSM ≥ 8.0 kPa) | 3 months | 
| Proportion of study participants with presumed any NASH | Proportion of study participants with presumed any NASH (fibrosis-4 index ≥1.3 or NAFLD fibrosis score >-1.455 AND FibroScan diagnosis of any stage fibrosis) | 3 months | 
| Proportion of study participants with presumed F2/F3 NASH | Proportion of study participants with presumed F2/F3 NASH (fibrosis-4 index ≥1.3 or NAFLD fibrosis score >-1.455 AND FibroScan diagnosis of F2/F3 fibrosis) | 3 months | 
| Proportion of study participants with a fibrosis-4 index (FIB-4) and/or NAFLD fibrosis score (NFS) above cut-off values | Proportion of study participants with a fibrosis-4 index (FIB-4) and/or NAFLD fibrosis score (NFS) above cut-off values (FIB-4 ≥1.3 or/and NFS >-1.455) | 1 day | 
| Proportion of study participants with a fibrosis and/or steatosis (stages) | Proportion of study participants with a fibrosis and/or steatosis (stages) based on FibroScan results | 1 day | 
| Alcohol consumption by study arm - drinks per day | Alcohol consumption measured as self-reported average drinks per day | 1 day | 
| Alcohol consumption by study arm - drinks per week | Alcohol consumption measured as self-reported average drinks per week | 1 day | 
| Alcohol consumption by study arm - Alcohol Use Disorders Identification Test (AUDIT) score | Alcohol consumption measured with the Alcohol Use Disorders Identification Test (AUDIT). AUDIT scores range from a minimum score of 0 to a maximum score of 40, with higher scores indicating a worse outcome. | 1 day | 
| Health-related quality of life by study arm | Health-related quality of life determined by the chronic liver disease questionnaire for non-alcoholic steatohepatitis (CLDQ-NASH) calculated as total CLDQ-NASH score. The CLDQ-NASH instrument includes 36 items grouped into six domains: abdominal symptoms; activity/energy; emotional health; fatigue; systemic symptoms; and worry. The average of the domain scores (min: 1, max: 7) yields the total CLDQ-NASH score. The minimum possible total score is 1 and the maximum possible total score is 7, with a higher total score indicating a better outcome. | 1 day |