Clinical trial NCT04595474: Prevalence of NAFLD and Advanced Fibrosis in Patients With Type 1 Diabetes
Official title: Assessing the Prevalence of Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in Patients With Type 1 Diabetes Using Vibration-Controlled Transient Elastography and Noninvasive Scores
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Nonalcoholic Fatty Liver
Nonalcoholic Steatohepatitis
Fibrosis, Liver
Type 1 Diabetes
Cirrhosis, Liver
Keywords: Nonalcoholic fatty liver disease (NAFLD)
Nonalcoholic steatohepatitis (NASH)
Type 1 Diabetes
Screening
Advanced fibrosis
Lead sponsor: Joslin Diabetes Center
Sponsor class: OTHER
First posted: 2020-10-20
Enrollment: 533
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will include subjects with type 1 diabetes receiving care at Joslin Diabetes Center. Addiotnal subjects from the broader Boston area may be recruited for the study.

Brief summary: The aim of this study is to assess the prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 1 diabetes receiving care at Joslin clinic using noninvasive imaging and serum-based methods with the goal of identifying high-risk patients with advanced fibrosis who should be prioritized for specialty referral

Detailed description: This is a prospective cohort, single-center, single-arm study screening adult subjects with type 1 diabetes from the Joslin Diabetes Center outpatient clinic mainly through physician referrals for NAFLD and advanced fibrosis. Subjects will undergo a one-time screening which will last for about 30 minutes.

The following procedures will be conducted during the study visit:

1. Blood draw for metabolic measurements (HbA1c, lipid panel, ALT, AST, serum albumin, complete blood count-CBC)
2. FibroScan Measurements (LSM and CAP)
3. Anthropometric measurements (weight, height, BMI calculation, waist, and hip circumference)
4. Systolic and diastolic blood pressure

Blood Draw:

Samples of blood taken during the trial for laboratory testing will include the following metabolic measurements: AST, ALT, Platelets, percentage A1C, and lipid parameters (TC, LDL, HDL, TG).

Fibroscan: Vibration controlled transient elastography (VCTE) or FibroScan® (EchoSens, Paris, France) is a simple aid to diagnose adult patients with chronic liver diseases. FibroScan provides a fast and reliable alternative to hepatic needle biopsy. In this 5-7 minute test, the investigator induces a mild amplitude shear wave into liver tissue from a small mechanical vibrator at the end of the FibroScan probe. VCTE evaluates a representative volume of the liver that is 100-fold greater than needle biopsy and the liver stiffness measurement (LSM) is expressed in kilopascals (kPa) with values \>9.8 kPa being consistent with the presence of advanced fibrosis/cirrhosis. Typically, 10 successful VCTE measurements with a median interquartile range/median ration of less than 30% are needed to have a reliable LSM.

FIB-4 Index: This is a noninvasive surrogate biomarker of advanced fibrosis that is calculated using the following formula:

FIB-4 = Age (years)×AST (U/L)/\[PLT(109/L)×√ALT(U/L)\] (Sterling, Lissen et al. 2006) FIB-4\>2.67 is consistent with the presence of advanced fibrosis with 80% PPV.

NAFLD Fibrosis Score (NFS): This is a noninvasive surrogate biomarker of advanced fibrosis that is calculated using the following formula:

NFS= -1.675 + 0.037 - age (years) + 0.094 - BMI (kg/m2) + 1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet count (×109/l) - 0.66 × albumin (g/dl).

NFS\>0.676 is consistent with the presence of advanced fibrosis

Anthropometric measurements: These include weight, height, BMI calculation, waist, and hip measurements. Measurements will be done using standardized anthropometric techniques.

Follow up may be required for High-risk patients with advanced fibrosis. If patient consents, referring or treating physicians will be notified and provided with fibroscan results for possible referral to hepatologists for further evaluation and intervention.

Eligibility criteria: Inclusion Criteria:

1. Subject is male or female
2. Subject age between 18-75 years old
3. Subject with an established diagnosis of T1D for at least three months prior to screening

Exclusion Criteria:

1. Subject is pregnant or lactating
2. Subject has an active malignancy

4.Subject with secondary causes of fatty liver including history of any of the following:

* Hepatitis B or C virus infection
* Wilson's disease
* Lipodystrophy
* Abetalipoproteinemia
* Current or previous use of any of the following medication: amiodarone, tamoxifen, methotrexate,corticosteroids (e.g. Prednisone), or Valproate
* Male subject consuming \>30 g of alcohol per day or female subject consuming \>20 g of alcohol perday

Primary outcomes:
measure: Proportion of subjects with NAFLD
timeFrame: Baseline (one time point evaluation)
measure: Proportion of subjects with advanced fibrosis
timeFrame: Baseline (one time point evaluation)
Secondary outcomes:
measure: Proportion of subjects with advanced fibrosis per NAFLD fibrosis score-NFS
timeFrame: Baseline (one time point evaluation)
measure: Proportion of subjects with advanced fibrosis per Fibrosis-4 (FIB-4) index
timeFrame: Baseline (one time point evaluation)
measure: HbA1c
timeFrame: Baseline (one time point evaluation)
measure: Anthropometrics
timeFrame: Baseline (one time point evaluation)
measure: Lipid profile
timeFrame: Baseline (one time point evaluation)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
Study officials:
affiliation: Joslin Diabetes Center
name: Osama Hamdy, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: