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

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

Study Overview

• Status: Recruiting
• Conditions: Obesity; Diabetes Mellitus; NAFLD
• Intervention / Treatment: 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

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Nikolaos Perakakis, MD; Phone Number: +4935145813651; Email: Nikolaos.Perakakis@ukdd.de
• Study Contact Backup: Name: Ingo Weigmann, MD; Phone Number: +4935145811723; Email: Ingo.Weigmann@ukdd.de

Study Locations

• Germany
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Recruiting
      • University Study Center for Metabolic Diseases
      • Contact: Nikolaos Perakakis, MD; Phone Number: +49 351 458 13651; Email: Nikolaos.Perakakis@ukdd.de
      • Contact: Ingo Weigmann, MD; Phone Number: +49 351 458 11723; Email: Ingo.Weigmann@ukdd.de
      • Principal Investigator: Nikolaos Perakakis, MD
      • Sub-Investigator: Ingo Weigmann, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• 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).

Description

Inclusion Criteria:

1. Age > 18 years old

Additional inclusion criteria for case groups:

1. High risk group for significant liver fibrosis

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

2. Steatotic Liver Disease group

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

3. 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

4. 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

   1. No steatosis in liver ultrasound AND CAP ≤ 275 dB/m C#) Normal glucose tolerance test group

   1. HbA1c < 5.7% AND
   2. Fasting glucose < 100 mg/dl AND
   3. Glucose at 120 min of OGTT <140 mg/dl

   Exclusion Criteria:

   1. Diabetes mellitus Typ 1
   2. BMI < 18.5 kg/m2
   3. Transfusion of blood or major bleeding in the last six months
   4. Anaemia with haemoglobin < 9,0 g/dl
   5. Chronic alcohol or drug abuse
   6. 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.)
   7. Systemic infections (CRP > 1 mg/dl)
   8. Medications that affect blood glucose levels (e.g. antidiabetics [except from the subjects forming the diabetes group], steroids) in the last six months
   9. Medications that affect coagulation (e.g. anticoagulants and antiplatelet agents) in the last six months
   10. Medications that affect immune function (e.g. immunosuppressive drugs) in the last six months
   11. Pregnancy or breastfeeding
   12. Severe psychic disorders
   13. Inability to follow the study protocol
   14. Have any medical condition unsuitable for inclusion in the study, in the opinion of the investigator

   Additional exclusion criteria for MRI:

   1. Pacemaker
   2. Artificial heart valve
   3. Metal prosthesis
   4. Implanted magnetic metal parts
   5. Spirals
   6. Fixed metal dental braces
   7. Acupuncture needle
   8. Insulin pumps
   9. By MRI > 3 Tesla: Tattoos, permanent eyeliner
   10. Claustrophobia or any other condition, such as psychiatric disorder, that in the opinion of the investigator may prevent the participant from following and completing the protocol
   11. Subject dimensions not allowing the performance of MRI

Study Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
High risk - Liver Fibrosis; FIB-4 score ≥ 1.3 AND; Fibroscan measurement ≥ 8kPa	Diagnostic test: Oral glucose tolerance test; 75g of a standardized glucose solution followed by blood draw at 0, 30, 60, 90, 120 min; Diagnostic test: Liver Ultrasound; A crude assessment of liver status in order to identify the presence of steatosis or not will take place with ultrasound.; Diagnostic test: Fibroscan of the Liver; 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).; Diagnostic test: Magentic Resonance Imaging (MRI) of the liver; The exact calculation of liver fat with proton density fat fraction will take place with MRI.
Low risk - Liver Fibrosis; Fibroscan measurements < 8kPa	Diagnostic test: Oral glucose tolerance test; 75g of a standardized glucose solution followed by blood draw at 0, 30, 60, 90, 120 min; Diagnostic test: Liver Ultrasound; A crude assessment of liver status in order to identify the presence of steatosis or not will take place with ultrasound.; Diagnostic test: Fibroscan of the Liver; 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).; Diagnostic test: Magentic Resonance Imaging (MRI) of the liver; The exact calculation of liver fat with proton density fat fraction will take place with MRI.
Steatotic Liver Disease; Diagnosis of steatosis in ultrasound AND CAP > 275 dB/m	Diagnostic test: Oral glucose tolerance test; 75g of a standardized glucose solution followed by blood draw at 0, 30, 60, 90, 120 min; Diagnostic test: Liver Ultrasound; A crude assessment of liver status in order to identify the presence of steatosis or not will take place with ultrasound.; Diagnostic test: Fibroscan of the Liver; 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).; Diagnostic test: Magentic Resonance Imaging (MRI) of the liver; The exact calculation of liver fat with proton density fat fraction will take place with MRI.
No Steatotic Liver Disease; No steatosis in liver ultrasound AND CAP ≤ 275 dB/m	Diagnostic test: Oral glucose tolerance test; 75g of a standardized glucose solution followed by blood draw at 0, 30, 60, 90, 120 min; Diagnostic test: Liver Ultrasound; A crude assessment of liver status in order to identify the presence of steatosis or not will take place with ultrasound.; Diagnostic test: Fibroscan of the Liver; 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).; Diagnostic test: Magentic Resonance Imaging (MRI) of the liver; The exact calculation of liver fat with proton density fat fraction will take place with MRI.
Diabetes; HbA1c ≥ 6.5% OR/AND; Fasting Glucose > 126 mg/dl OR/AND; 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; 75g of a standardized glucose solution followed by blood draw at 0, 30, 60, 90, 120 min; Diagnostic test: Liver Ultrasound; A crude assessment of liver status in order to identify the presence of steatosis or not will take place with ultrasound.; Diagnostic test: Fibroscan of the Liver; 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).; Diagnostic test: Magentic Resonance Imaging (MRI) of the liver; The exact calculation of liver fat with proton density fat fraction will take place with MRI.
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	Diagnostic test: Oral glucose tolerance test; 75g of a standardized glucose solution followed by blood draw at 0, 30, 60, 90, 120 min; Diagnostic test: Liver Ultrasound; A crude assessment of liver status in order to identify the presence of steatosis or not will take place with ultrasound.; Diagnostic test: Fibroscan of the Liver; 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).; Diagnostic test: Magentic Resonance Imaging (MRI) of the liver; The exact calculation of liver fat with proton density fat fraction will take place with MRI.
Normal glucose tolerance; HbA1c < 5.7% AND; Fasting glucose < 100 mg/dl AND; Glucose at 120 min of OGTT <140 mg/dl and no history of Diabetes	Diagnostic test: Oral glucose tolerance test; 75g of a standardized glucose solution followed by blood draw at 0, 30, 60, 90, 120 min; Diagnostic test: Liver Ultrasound; A crude assessment of liver status in order to identify the presence of steatosis or not will take place with ultrasound.; Diagnostic test: Fibroscan of the Liver; 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).; Diagnostic test: Magentic Resonance Imaging (MRI) of the liver; The exact calculation of liver fat with proton density fat fraction will take place with MRI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Qualitative differences in platelets	% of Platelet aggregation	1 day
Quantitative differences in platelets	Platelet count in GPt/L	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative differences in leukocytes	Leucocyte count in GPt/L	1 day
Quantitative differences in neutrophils	Neutrophil count in GPt/L	1 day
Quantitative differences in lymphocytes	Lymphocyte count in GPt/L	1 day
Quantitative differences in monocytes	Monocyte count in GPt/L	1 day
Qualitative differences in neutrophils in NETosis	% of neutrophils performing NETosis (FACS analysis)	1 day
Qualitative differences in neutrophils in phagocytosis	% of neutrophils performing phagocytosis (FACS analysis)	1 day
Qualitative differences in monocytes	% of monocytes performing phagocytosis (FACS analysis)	1 day
Quantitative differences in Interleukin-6	Interleukin-6 in pg/ml	1 day
Quantitative differences in Interleukin-8	Interleukin-8 in pg/ml	1 day

Collaborators and Investigators

• Sponsor: Technische Universität Dresden

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Actual): May 2, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematinics; Liver Extracts
• Other Study ID Numbers: BO-EK-508112022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD and biospecimens in pseudonymized form might be shared with other researchers upon written request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No