Clinical trial NCT06396871: Deep Phenotyping of Peripheral Blood Cells and Circulating Factors in Metabolic Diseases
Official title: Deep Phenotyping of Peripheral Blood Cells and Circulating Factors in Metabolic Diseases
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: NAFLD
Diabetes Mellitus
Obesity
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
First posted: 2024-05-02
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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).

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


Eligibility criteria: 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

Primary outcomes:
measure: Qualitative differences in platelets
timeFrame: 1 day
measure: Quantitative differences in platelets
timeFrame: 1 day
Secondary outcomes:
measure: Quantitative differences in leukocytes
timeFrame: 1 day
measure: Quantitative differences in neutrophils
timeFrame: 1 day
measure: Quantitative differences in lymphocytes
timeFrame: 1 day
measure: Quantitative differences in monocytes
timeFrame: 1 day
measure: Qualitative differences in neutrophils in NETosis
timeFrame: 1 day
measure: Qualitative differences in neutrophils in phagocytosis
timeFrame: 1 day
measure: Qualitative differences in monocytes
timeFrame: 1 day
measure: Quantitative differences in Interleukin-6
timeFrame: 1 day
measure: Quantitative differences in Interleukin-8
timeFrame: 1 day
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: University Study Center for Metabolic Diseases
state: Saxony
Study officials:
References: