Mitochondrial Function
Conditions
Keywords
Mitochondrial respiration, PBMC
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.
Interventions
OTHERVenipuncture
Blood drawing
OTHERQuestionnaire
Completion of the questionnaire
Sponsors
Oroboros Instruments
VASCage GmbH
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged between 18-85 * Willingness and ability to consent
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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) |
| Concentration of triglyceride and cholesterol | Baseline, 6, 12 months visit | Triglyceride (mmol/L), cholesterol (all, mmol/L ) |
| Concentration of LDL-cholesterol and HDL-cholesterol | Baseline, 6, 12 months visit | LDL-cholesterol (mg/dL), HDL-cholesterol (mg/dL) |
| Concentration of Lipoprotein a | Baseline visit | Lipoprotein a (mg/dL) |
| Assessment of Sedimentation rate | Baseline, 12 months visit | Sedimentation rate (mm/h) |
| Concentration of Ferritin | Baseline, 12 months visit | Ferritin (ng/mL, μg/L) |
| 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 Thyroid-stimulating hormone | Baseline, 12 months visit | TSH (mU/mL) |
| Concentration of Iric acid | Baseline, 12 months visit | Uric acid (mg/dL) |
| 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 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 |
| 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)) |
| 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 Glucose | Baseline visit, 3, 6, 9, 12 months visit | Glucose (mg/dL, mmol/L) |
| Concentration of HbA1c | Baseline, 6, 12 months visit | HbA1c (%) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Menstrual cycle length (women only) | Baseline visit, 3, 6, 9, 12 months visit | Assessment of menstrual cycle with focus on the initiation of the last cycle (day) |
| Demographic data - Personal background and lifestyle II | Baseline visit, 3, 6, 9, 12 months visit | Assessment of demographic data with focus on personal background and lifestyle: smoking and smoking history, alcohol consumption and diet |
| Demographic data - Personal background and lifestyle III | Baseline visit, 3, 6, 9, 12 months visit | Assessment of demographic data with focus on personal background and lifestyle: amount and intensity of physical activity |
| Demographic data - Personal background and lifestyle IV | Baseline visit, 3, 6, 9, 12 months visit | Assessment of personal background and lifestyle: sleep quality |
| Medical History Assessment | Baseline visit, 3, 6, 9, 12 months visit | Assessment of medical history: * pre-existing illnesses * current illnesses or allergies * chronic illnesses * medication * previous surgical procedures within the last 2 years |
| Assessment of mental well-being using the Hospital Anxiety and Depression Scale - German Version (HADS-D) questionnaire | Baseline visit, 3, 6, 9, 12 months visit | The questionnaire uses an anxiety scale and a depression scale (0-21, each). The higher the value, the more anxious/depressed the patient. Cut-off for clinical significance: ≥8 |
| Demographic data III | Baseline visit | Assessment of demographic data such as: weight (kg) |
| Demographic data I | Baseline visit | Assessment of demographic data such as current age, sex at birth, location of birth |
| Demographic data II | Baseline visit | Assessment of demographic data such as: height (cm) |
| Menstrual cycle duration (women only) | Baseline visit, 3, 6, 9, 12 months visit | Assessment of menstrual cycle with focus on cycle duration (in days) |
| Demographic data - Personal background and lifestyle I | Baseline visit | Assessment of demographic data with focus on personal background and lifestyle: e.g. * ethnicity (anamnesis) * marital/relationship status (anamnesis) * number of children (anamnesis) * highest level of education (anamnesis) |
Countries
Austria
Outcome results
None listed