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

Primary Purpose

Nonalcoholic Steatohepatitis, Type 2 Diabetes

Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
routine screening
physician-driven screening
Sponsored by
LMC Diabetes & Endocrinology Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Nonalcoholic Steatohepatitis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • LMC Diabetes & Endocrinology Ltd.Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

routine screening group

physician-driven screening group

Arm Description

consists of 4 clusters randomized into Group 1 (includes different clinic sites from Group 2)

consists of 4 clusters randomized into Group 2 (includes different clinic sites from Group 1)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Proportion of study participants with presumed any NASH
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
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
Alcohol consumption measured as self-reported average drinks per day
Alcohol consumption by study arm - drinks per week
Alcohol consumption measured as self-reported average drinks per week
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.
Change in health-related quality of life at 36 months among participants with stage F3-F4 compared to stage F0-F2
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Alcohol consumption measured as self-reported average drinks per day at 36 months
Alcohol consumption at 36 months - drinks per week
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
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.

Full Information

First Posted
August 19, 2021
Last Updated
August 25, 2021
Sponsor
LMC Diabetes & Endocrinology Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05029583
Brief Title
Clinical Outcomes From Enhanced SCREENing Strategies for Advanced NASH in Type 2 Diabetes (SCREEN NASH T2D)
Official Title
A Cluster Randomized Trial to Determine Diagnostic and Clinical Outcomes From Enhanced SCREENing Strategies for Advanced NASH in Type 2 Diabetes (SCREEN NASH T2D)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 11, 2021 (Actual)
Primary Completion Date
March 1, 2023 (Anticipated)
Study Completion Date
June 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LMC Diabetes & Endocrinology Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Steatohepatitis, Type 2 Diabetes

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Care Provider
Masking Description
The care provider is masked to the primary outcome of the study, but not masked to the intervention.
Allocation
Randomized
Enrollment
5000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
routine screening group
Arm Type
Experimental
Arm Description
consists of 4 clusters randomized into Group 1 (includes different clinic sites from Group 2)
Arm Title
physician-driven screening group
Arm Type
Active Comparator
Arm Description
consists of 4 clusters randomized into Group 2 (includes different clinic sites from Group 1)
Intervention Type
Other
Intervention Name(s)
routine screening
Intervention Description
routine screening for advanced NASH
Intervention Type
Other
Intervention Name(s)
physician-driven screening
Intervention Description
physician-driven screening for advanced NASH
Primary Outcome Measure Information:
Title
Prevalence of presumed advanced NASH based on biochemical and FibroScan results
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Proportion of study participants with presumed any NASH
Description
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)
Time Frame
3 months
Title
Proportion of study participants with a fibrosis-4 index (FIB-4) and/or NAFLD fibrosis score (NFS) above cut-off values
Description
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)
Time Frame
1 day
Title
Alcohol consumption by study arm - drinks per day
Description
Alcohol consumption measured as self-reported average drinks per day
Time Frame
1 day
Title
Alcohol consumption by study arm - drinks per week
Description
Alcohol consumption measured as self-reported average drinks per week
Time Frame
1 day
Title
Alcohol consumption by study arm - Alcohol Use Disorders Identification Test (AUDIT) score
Description
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.
Time Frame
1 day
Title
Change in health-related quality of life at 36 months among participants with stage F3-F4 compared to stage F0-F2
Description
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.
Time Frame
36 months
Title
Change in glycated hemoglobin (HbA1c) at 36 months among participants with stage F3-F4
Description
Change in glycated hemoglobin (HbA1c) in percent at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
Time Frame
36 months
Title
Change in body mass index (BMI) at 36 months among participants with stage F3-F4
Description
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.
Time Frame
36 months
Title
Change in waist circumference measurement at 36 months among participants with stage F3-F4
Description
Change in waist circumference in cm at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
Time Frame
36 months
Title
Change in systolic blood pressure at 36 months among participants with stage F3-F4
Description
Change in systolic blood pressure in mmHg at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
Time Frame
36 months
Title
Change in diastolic blood pressure at 36 months among participants with stage F3-F4
Description
Change in diastolic blood pressure in mmHg at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
Time Frame
36 months
Title
Change in number of diabetes medications at 36 months among participants with stage F3-F4
Description
Change in total number of diabetes medications at 36 months from baseline among participants with stage F3-F4 compared to stage F0-F2.
Time Frame
36 months
Title
Change in fibrosis-4 index (FIB-4) at 36 months among participants with stage F3-F4
Description
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]))
Time Frame
36 months
Title
Change in NAFLD fibrosis score (NFS) at 36 months among participants with stage F3-F4
Description
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])
Time Frame
36 months
Title
Change in liver stiffness measure (LSM) at 36 months among participants with stage F3-F4
Description
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.
Time Frame
36 months
Title
Change in controlled attenuation parameter (CAP) score at 36 months among participants with stage F3-F4
Description
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.
Time Frame
36 months
Title
Change in FibroScan-AST (FAST) score at 36 months among participants with stage F3-F4
Description
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)
Time Frame
36 months
Title
Comparison of any stage fibrosis
Description
Proportion of patients with FibroScan diagnosis of any stage fibrosis at 36-months compared to baseline
Time Frame
36 months
Title
Comparison of fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) above cut-offs
Description
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
Time Frame
36 months
Title
Proportion of patients who undergo liver biopsy and have a diagnosis of any stage fibrosis at 36 months
Description
Proportion of patients who undergo liver biopsy and have a diagnosis of any stage fibrosis at 36 months
Time Frame
36 months
Title
Health-related quality of life at 36-months compared to baseline
Description
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.
Time Frame
36 months
Title
Patient adherence to care path
Description
Patient adherence to care path based on proportion of appointments attended for patients referred to diabetes and NASH education and a hepatologist
Time Frame
36 months
Title
Alcohol consumption at 36 months - drinks per day
Description
Alcohol consumption measured as self-reported average drinks per day at 36 months
Time Frame
36 months
Title
Alcohol consumption at 36 months - drinks per week
Description
Alcohol consumption measured as self-reported average drinks per week at 36 months
Time Frame
36 months
Title
Alcohol consumption at 36 months - Alcohol Use Disorders Identification Test (AUDIT) score
Description
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.
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa Chu, PhD
Phone
416-268-8787
Email
lisa.chu@LMC.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Karri Venn
Phone
647-274-4133
Email
karri.venn@lmcmanna.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harpreet Bajaj, MD
Organizational Affiliation
LMC Diabetes & Endocrinology Ltd.
Official's Role
Principal Investigator
Facility Information:
Facility Name
LMC Diabetes & Endocrinology Ltd.
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4G 3E8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Chu, PhD
Phone
416-268-8787
Email
lisa.chu@lmc.ca
First Name & Middle Initial & Last Name & Degree
Karri Venn
Phone
647-274-4133
Email
karri.venn@lmcmanna.com
First Name & Middle Initial & Last Name & Degree
Harpreet Bajaj, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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