Deep Phenotyping of Peripheral Blood Cells and Circulating Factors in Metabolic Diseases

NCT06396871 | Recruiting

• 1 other identifier: BO-EK-508112022
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this cross-sectional observational study is to to perform a thorough characterization of the quantitative and qualitative differences in peripheral blood cells, and circulating factors (proteins, metabolites, lipids, extracellular vesicles) in different stages of several metabolic diseases (diabetes, obesity, non-alcoholic fatty liver disease) that share common pathophysiological mechanisms and in comparison with adult healthy controls. The main question\[s\] it aims to answer are:

• Which are the quantitative (number and concentration) and qualtitative (characteristics, functional assays) differences in platelets in patients with metabolic diseases vs subjects without metabolic diseases
• Which are the quantitative (number and concentration) and qualtitative (characteristics, functional assays) differences in leucocytes or circulating molecules in patients with metabolic diseases vs subjects without metabolic diseases

Conditions

NAFLD; Diabetes Mellitus; Obesity

Outcome Measures

Primary Outcomes (2)

• Qualitative differences in platelets

  % of Platelet aggregation

  1 day

• Quantitative differences in platelets

  Platelet count in GPt/L

  1 day

Secondary Outcomes (9)

• Quantitative differences in leukocytes

  1 day

• Quantitative differences in neutrophils

  1 day

• Quantitative differences in lymphocytes

  1 day

• Quantitative differences in monocytes

  1 day

• Qualitative differences in neutrophils in NETosis

  1 day

Study Arms (7)

High risk - Liver Fibrosis

1. FIB-4 score ≥ 1.3 AND 2. Fibroscan measurement ≥ 8kPa

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Liver Ultrasound; Diagnostic Test: Fibroscan of the Liver; Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Low risk - Liver Fibrosis

Fibroscan measurements \< 8kPa

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Liver Ultrasound; Diagnostic Test: Fibroscan of the Liver; Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Steatotic Liver Disease

Diagnosis of steatosis in ultrasound AND CAP \> 275 dB/m

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Liver Ultrasound; Diagnostic Test: Fibroscan of the Liver; Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

No Steatotic Liver Disease

No steatosis in liver ultrasound AND CAP ≤ 275 dB/m

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Liver Ultrasound; Diagnostic Test: Fibroscan of the Liver; Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Diabetes

1. HbA1c ≥ 6.5% OR/AND 2. Fasting Glucose \> 126 mg/dl OR/AND 3. Glucose at 120 min of OGTT \> 200 mg/dl AND/OR history of Diabetes, treated with at least one antidiabetic medication

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Liver Ultrasound; Diagnostic Test: Fibroscan of the Liver; Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Prediabetes

1. HbA1c \>5.7 AND \<6.5% OR/AND 2. Fasting Glucose 100-125 mg/dl OR/AND 3. Glucose at 120 min of OGTT between 140-200 mg/dl

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Liver Ultrasound; Diagnostic Test: Fibroscan of the Liver; Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Normal glucose tolerance

1. HbA1c \< 5.7% AND 2. Fasting glucose \< 100 mg/dl AND 3. Glucose at 120 min of OGTT \<140 mg/dl and no history of Diabetes

Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Liver Ultrasound; Diagnostic Test: Fibroscan of the Liver; Diagnostic Test: Magentic Resonance Imaging (MRI) of the liver

Interventions

Oral glucose tolerance test DIAGNOSTIC_TEST

75g of a standardized glucose solution followed by blood draw at 0, 30, 60, 90, 120 min

Diabetes; High risk - Liver Fibrosis; Low risk - Liver Fibrosis; No Steatotic Liver Disease; Normal glucose tolerance; Prediabetes; Steatotic Liver Disease

Liver Ultrasound DIAGNOSTIC_TEST

A crude assessment of liver status in order to identify the presence of steatosis or not will take place with ultrasound.

Diabetes; High risk - Liver Fibrosis; Low risk - Liver Fibrosis; No Steatotic Liver Disease; Normal glucose tolerance; Prediabetes; Steatotic Liver Disease

Fibroscan of the Liver DIAGNOSTIC_TEST

FibroScan non-invasively measures the stiffness of the liver by capturing and calculating the speed of a shear wave as it travels through the liver (vibration controlled transient elastography).

Diabetes; High risk - Liver Fibrosis; Low risk - Liver Fibrosis; No Steatotic Liver Disease; Normal glucose tolerance; Prediabetes; Steatotic Liver Disease

Magentic Resonance Imaging (MRI) of the liver DIAGNOSTIC_TEST

The exact calculation of liver fat with proton density fat fraction will take place with MRI.

Diabetes; High risk - Liver Fibrosis; Low risk - Liver Fibrosis; No Steatotic Liver Disease; Normal glucose tolerance; Prediabetes; Steatotic Liver Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population will include subjects belonging to one of the 7 investigation groups. The same subject might belong simultaneously to more than one group (i.e. to fibrosis or no fibrosis group, to steatotic liver disease or no steatotic liver disease group and to normal glucose tolerance, prediabetes or diabetes).

You may qualify if:

• \. Age \> 18 years old
• High risk group for significant liver fibrosis
• \. FIB-4 score ≥ 1.3 AND 2. Fibroscan measurement ≥ 8kPa
• Steatotic Liver Disease group
• \. Diagnosis of steatosis in ultrasound AND CAP \> 275 dB/m
• Prediabetes
• HbA1c \>5.7 AND \<6.5% OR/AND
• Fasting Glucose 100-125 mg/dl OR/AND
• Glucose at 120 min of OGTT between 140-200 mg/dl
• Diabetes 1. HbA1c ≥ 6.5% OR/AND 2. Fasting Glucose \> 126 mg/dl OR/AND 3. Glucose at 120 min of OGTT \> 200 mg/dl
• If a subject does not fulfil the additional criteria for participating in a case group, then he/she will be included in the respective control group which will be:
• A#) Low risk for significant liver fibrosis 1. Fibroscan measurements \< 8kPa B#) No steatosis group
• \. No steatosis in liver ultrasound AND CAP ≤ 275 dB/m C#) Normal glucose tolerance test group
• HbA1c \< 5.7% AND
• Fasting glucose \< 100 mg/dl AND

You may not qualify if:

• Diabetes mellitus Typ 1
• BMI \< 18.5 kg/m2
• Transfusion of blood or major bleeding in the last six months
• Anaemia with haemoglobin \< 9,0 g/dl
• Chronic alcohol or drug abuse
• Presence of any acute or chronic liver disease apart from non-alcoholic fatty liver disease (i.e. viral, autoimmune or alcoholic hepatitis, haemochromatosis, Morbus Wilson etc.)
• Systemic infections (CRP \> 1 mg/dl)
• Medications that affect blood glucose levels (e.g. antidiabetics \[except from the subjects forming the diabetes group\], steroids) in the last six months
• Medications that affect coagulation (e.g. anticoagulants and antiplatelet agents) in the last six months
• Medications that affect immune function (e.g. immunosuppressive drugs) in the last six months
• Pregnancy or breastfeeding
• Severe psychic disorders
• Inability to follow the study protocol
• Pacemaker
• Artificial heart valve

Sponsors & Collaborators

• Technische Universität Dresden: lead

Study Sites (1)

University Study Center for Metabolic Diseases

Dresden, Saxony, 01307, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, Serum, Peripheral Blood Mononuclear Cells, Neutrophils, DNA

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus; Obesity

Interventions

Glucose Tolerance Test; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Tomography; Diagnostic Imaging

Central Study Contacts

Nikolaos Perakakis, MD

CONTACT

+4935145813651; Nikolaos.Perakakis@ukdd.de

Ingo Weigmann, MD

CONTACT

+4935145811723; Ingo.Weigmann@ukdd.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2023
• First Posted: May 2, 2024
• Study Start: October 16, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 2, 2024

Record last verified: 2024-04

Locations

DE (1)