Functional Mitochondrial Analysis PBMCs
- Conditions
- Mitochondrial Function
- Registration Number
- NCT06498791
- Lead Sponsor
- VASCage GmbH
- Brief Summary
The primary goal of this prospective, exploratory, longitudinal, single-centre, cohort study is to assess the stability of the mitochondrial flux in PBMCs over long-term cryopreservation.
Secondary goals of this study are:
* to identify changes in the mitochondrial respiratory flux in different metabolic states of cryopreserved PBMCs during long-term cryopreservation.
* to assess variability between mitochondrial respiration from PBMCs isolated from same volunteers at different times, seasons or from different arms.
- Detailed Description
The analysis of mitochondrial function can also be referred to as a bioenergetic snapshot. Mitochondria are dynamic metabolic organelles that adapt to various physiological demands, reflecting an individual's lifestyle and exposure to environmental factors, medications, and toxins. Numerous studies have shown that mitochondrial respiration declines with age and correlates with many age-related diseases. This raises the question of how mitochondria influence cells in a clinical context.
For this purpose, 20 participants are recruited and comprehensively characterized in terms of their demographic information and clinical profiles. Additionally, physical examinations are conducted, and participants are surveyed about their lifestyles through questionnaires. Over a 12-month period, blood samples are collected at intervals of three months, resulting in a total of five study visits. For the analysis of mitochondrial oxygen consumption, peripheral blood mononuclear cells (PBMCs) are preferably used, as they provide a minimally invasive and easily accessible insight into mitochondrial function and overall metabolic status and are isolated from the collected blood samples.
To enable the application of mitochondrial diagnostics in research for early disease detection and therapeutic development, additional information is needed regarding the stability of mitochondrial respiration in cryopreserved PBMCs using high-resolution respirometry (HRR) with O2k technology. The goal of this study is to assess how the duration of cryopreservation affects mitochondrial bioenergetics compared to freshly isolated PBMCs.
The study also considers a variety of parameters that could potentially influence the stability of mitochondrial respiration. These factors include non-fasting blood collection, discrepancies between the right and left arm, and seasonal effects. To what extent the intraindividual variability in these parameters affects the mitochondrial respiration is yet to be fully understood.
Furthermore, the longitudinal study design allows the tracking of mitochondrial activity and stability over time, providing a better understanding of the central processes of cellular respiration.
Thus, the planned study promises to yield significant insights into mitochondrial respiration and cellular bioenergetics in a clinical context.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 20
- Aged between 18-85
- Willingness and ability to consent
- Regular (e.g. daily, weekly or similar) intake of medication or nutritional supplements except oral and spiral contraceptives
- Autoimmune diseases or immune alterations
- Diseases in the context of haematopoiesis, haemophilia, hematophobia
- Diagnosed mild or major neurocognitive disorder
- Depressive episodes in the last two years
- Chronic infectious diseases
- Neurostimulators or drug pump
- Involved in competitive sports (over the past two years)
- Pregnancy
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Stability of mitochondrial respiratory flux (O2 flux) in cryopreserved PBMCs 1 week and every 8 weeks after cryopreservation Mitochondrial respiratory flux is assessed by High Resolution Respirometry analysis
Stability of O2 concentration in cryopreserved PBMCs 1 week and every 8 weeks after cryopreservation Mitochondrial respiratory flux is assessed by High Resolution Respirometry analysis
Assessment of mitochondrial respiratory flux (O2 flux) in fresh PBMCs compared to cryopreserved PBMCs Baseline visit, 3, 6, 9, 12 months visit Mitochondrial respiratory flux is assessed by High Resolution Respirometry analysis
Assessment of O2 concentration in fresh PBMCs compared to cryopreserved PBMCs Baseline visit, 3, 6, 9, 12 months visit Mitochondrial respiratory flux is assessed by High Resolution Respirometry analysis
- Secondary Outcome Measures
Name Time Method Concentration of HbA1c Baseline, 6, 12 months visit HbA1c (%)
Concentration of triglyceride and cholesterol Baseline, 6, 12 months visit Triglyceride (mmol/L), cholesterol (all, mmol/L )
Assessment of Sedimentation rate Baseline, 12 months visit Sedimentation rate (mm/h)
Assessment of O2 flux in fresh and cryopreserved PBMCs in fasted vs non-fasted sampling conditions 6 months visit Assessement of mitochondrial bioenergetic snapshot in fresh and cryopreserved PBMCs at two different collection time points (fasted and non-fasted)
Assessment of blood count and differential blood count II Baseline visit, 3, 6, 9, 12 months visit Analysis of complete blood count (e.g. haemoglobin concentration (g/dL))
Concentration of Creatinine and Urea Baseline visit, 3, 6, 9, 12 months visit Creatinine (mg/dL), Urea (mg/dL)
Concentration of Thyroid-stimulating hormone Baseline, 12 months visit TSH (mU/mL)
Concentration of Creatine Kinase Baseline, 6, 12 months visit Creatine Kinase (U/L)
Concentration of Sodium, Potassium, Chloride and Calcium Baseline, 6, 12 months visit Sodium (mmol/L), potassium (mmol/L), chloride (mmol/L), calcium (mmol/L)
Concentration of Lipoprotein a Baseline visit Lipoprotein a (mg/dL)
Assessment of blood count and differential blood count I Baseline visit, 3, 6, 9, 12 months visit Analysis of complete blood count (e.g. erythrocyte concentration (mg/dL))
Concentration of GOT and GPT Baseline, 6, 12 months visit Glutamic-oxaloacetic transaminase (GOT, U/L), glutamic-pyruvic transaminase (GPT, U/L), gamma-glutamyl-transpeptidase (gamma-GT, U/L), lactate dehydrogenase (LDH, U/L)
Assessment of O2 flux in fresh and cryopreserved PBMCs at different seasonal collection time points Baseline visit, 3, 6, 9, 12 months visit Assessement of mitochondrial bioenergetic snapshot in fresh and cryopreserved PBMCs in different seasons
Assessment of O2 flux in fresh and cryopreserved PBMCs at different venipuncture sites 3 months visit Assessement of mitochondrial bioenergetic snapshot in fresh and cryopreserved PBMCs collected from left and right arm
Concentration of Glucose Baseline visit, 3, 6, 9, 12 months visit Glucose (mg/dL, mmol/L)
Concentration of LDL-cholesterol and HDL-cholesterol Baseline, 6, 12 months visit LDL-cholesterol (mg/dL), HDL-cholesterol (mg/dL)
Concentration of C-reactive protein Baseline visit, 3, 6, 9, 12 months visit CRP sensitive (mg/L)
Concentration of Interleukin-6 Baseline, 6, 12 months visit Interleukin-6 (pg/ml)
Concentration of Iric acid Baseline, 12 months visit Uric acid (mg/dL)
Concentration of Ferritin Baseline, 12 months visit Ferritin (ng/mL, μg/L)
Trial Locations
- Locations (1)
Medical University Innsbruck - Department of Neurology
🇦🇹Innsbruck, Tyrol, Austria