Clinical Outcomes From Enhanced SCREENing Strategies for Advanced NASH in Type 2 Diabetes (SCREEN NASH T2D)
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
The study consists of two phases. For Phase 1, 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 undergo biochemical screening. In Phase 2, all participants, regardless of randomization, meeting biochemical cut-offs (FIB-4 index >2.67 or NFS >0.675) will undergo FibroScans at Phase 2 initiation and at the 36-month follow-up visit. Clinical data and a health-related quality of life assessment are collected at baseline and 36 months. A prospective NASH registry will be created from the participant data collected in Phase 2.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: routine screening group consists of 4 clusters randomized into Group 1 (includes different clinic sites from Group 2) |
Other: routine screening
routine screening for advanced NASH
|
| Active Comparator: physician-driven screening group consists of 4 clusters randomized into Group 2 (includes different clinic sites from Group 1) |
Other: physician-driven screening
physician-driven screening for advanced NASH
|
Outcome Measures
Primary Outcome Measures
- Prevalence of presumed advanced NASH based on biochemical and FibroScan results [3 months]
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.
Secondary Outcome Measures
- Proportion of study participants with presumed any NASH [3 months]
Proportion of study participants with presumed any NASH (fibrosis-4 index >2.67 or NAFLD fibrosis score >0.675 AND FibroScan diagnosis of any stage fibrosis)
- Proportion of study participants with a fibrosis-4 index (FIB-4) and/or NAFLD fibrosis score (NFS) above cut-off values [1 day]
Proportion of study participants with a fibrosis-4 index (FIB-4) and/or NAFLD fibrosis score (NFS) above cut-off values (FIB-4 >2.67 or/and NFS >0.675)
- Alcohol consumption by study arm - drinks per day [1 day]
Alcohol consumption measured as self-reported average drinks per day
- Alcohol consumption by study arm - drinks per week [1 day]
Alcohol consumption measured as self-reported average drinks per week
- Alcohol consumption by study arm - Alcohol Use Disorders Identification Test (AUDIT) score [1 day]
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.
- Change in health-related quality of life at 36 months among participants with stage F3-F4 compared to stage F0-F2 [36 months]
Change in health-related quality of life determined by the chronic liver disease questionnaire for non-alcoholic steatohepatitis (CLDQ-NASH) calculated as total CLDQ-NASH score at 36 months minus CLDQ-NASH score at baseline among participants with stage F3-F4 compared to stage F0-F2. 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. A greater change in CLDQ-NASH score at 36-months from baseline would indicate a greater improvement in health-related quality of life.
- Change in glycated hemoglobin (HbA1c) at 36 months among participants with stage F3-F4 [36 months]
Change in glycated hemoglobin (HbA1c) in percent at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
- Change in body mass index (BMI) at 36 months among participants with stage F3-F4 [36 months]
Change in body mass index (BMI) in kg/m2 at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2. Measured weight in kg and height in m will be combined to calculate BMI in kg/m2.
- Change in waist circumference measurement at 36 months among participants with stage F3-F4 [36 months]
Change in waist circumference in cm at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
- Change in systolic blood pressure at 36 months among participants with stage F3-F4 [36 months]
Change in systolic blood pressure in mmHg at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
- Change in diastolic blood pressure at 36 months among participants with stage F3-F4 [36 months]
Change in diastolic blood pressure in mmHg at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
- Change in number of diabetes medications at 36 months among participants with stage F3-F4 [36 months]
Change in total number of diabetes medications at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
- Change in fibrosis-4 index (FIB-4) at 36 months among participants with stage F3-F4 [36 months]
Change in fibrosis-4 index (FIB-4) at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2. FIB-4 calculation: (age[years]*AST[U/L])/(platelet[10^9]*SQRT(ALT[U/L]))
- Change in NAFLD fibrosis score (NFS) at 36 months among participants with stage F3-F4 [36 months]
Change in NAFLD fibrosis score (NFS) at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2. NFS calculation: -1.675 + (0.037* Age[years]) + (0.094*BMI[kg/m2] + (1.13* IFG/diabetes [yes=1, no=0]) + (0.99*AST/ALT) - (0.013*platelet[10^9] - (0.66*albumin[g/dL])
- Change in liver stiffness measure (LSM) at 36 months among participants with stage F3-F4 [36 months]
Change in liver stiffness measure (LSM) in kPa at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2. LSM is measured with FibroScan testing.
- Change in controlled attenuation parameter (CAP) score at 36 months among participants with stage F3-F4 [36 months]
Change in controlled attenuation parameter (CAP) at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2. CAP score is measured with FibroScan testing.
- Change in FibroScan-AST (FAST) score at 36 months among participants with stage F3-F4 [36 months]
Change in FibroScan-AST (FAST) score at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2. FAST score calculation: e^(-1.65+1.07*ln(liver stiffness measure[kPa]) + 2.66*10^-8*(controlled attenuation parameter[dB/m])^3 - 63.3*AST^-1)/1 + e^(-1.65+1.07*ln(liver stiffness measure[kPA]) + 2.66*10^-8*(controlled attenuation parameter[dB/m])^3 - 63.3*AST^-1)
- Comparison of any stage fibrosis [36 months]
Proportion of patients with FibroScan diagnosis of any stage fibrosis at 36-months compared to baseline
- Comparison of fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) above cut-offs [36 months]
Proportion of patients with a fibrosis-4 index (FIB-4) and/or NAFLD fibrosis score (NFS) above cut-off values indicating advanced fibrosis at 36-months compared to baseline
- Proportion of patients who undergo liver biopsy and have a diagnosis of any stage fibrosis at 36 months [36 months]
Proportion of patients who undergo liver biopsy and have a diagnosis of any stage fibrosis at 36 months
- Health-related quality of life at 36-months compared to baseline [36 months]
Health-related quality of life determined by the chronic liver disease questionnaire for non-alcoholic steatohepatitis (CLDQ-NASH) at 36-months compared to baseline. 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.
- Patient adherence to care path [36 months]
Patient adherence to care path based on proportion of appointments attended for patients referred to diabetes and NASH education and a hepatologist
- Alcohol consumption at 36 months - drinks per day [36 months]
Alcohol consumption measured as self-reported average drinks per day at 36 months
- Alcohol consumption at 36 months - drinks per week [36 months]
Alcohol consumption measured as self-reported average drinks per week at 36 months
- Alcohol consumption at 36 months - Alcohol Use Disorders Identification Test (AUDIT) score [36 months]
Alcohol consumption measured with the Alcohol Use Disorders Identification Test (AUDIT) at 36 months of follow-up. AUDIT scores range from a minimum score of 0 to a maximum score of 40, with higher scores indicating a worse outcome.
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | LMC Diabetes & Endocrinology Ltd. | Toronto | Ontario | Canada | M4G 3E8 |
Sponsors and Collaborators
- LMC Diabetes & Endocrinology Ltd.
Investigators
- Principal Investigator: Harpreet Bajaj, MD, LMC Diabetes & Endocrinology Ltd.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SCREEN NASH T2D