Clinical trial NCT06498791: Functional Mitochondrial Analysis PBMCs
Official title: Functional Mitochondrial Analysis of Peripheral Blood Mononuclear Cells (PBMCs) - a Pilot Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Mitochondrial Function
Keywords: Mitochondrial respiration
PBMC
Lead sponsor: VASCage GmbH
Sponsor class: OTHER
Collaborators: name: Oroboros Instruments
First posted: 2024-07-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The source population for this study comprises adults (older than 18 years of age) with an equal distribution of male and female.

Overall, 20 individuals will be included in the study (10 male, 10 female).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Stability of mitochondrial respiratory flux (O2 flux) in cryopreserved PBMCs
timeFrame: 1 week and every 8 weeks after cryopreservation
measure: Stability of O2 concentration in cryopreserved PBMCs
timeFrame: 1 week and every 8 weeks after cryopreservation
measure: Assessment of mitochondrial respiratory flux (O2 flux) in fresh PBMCs compared to cryopreserved PBMCs
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Assessment of O2 concentration in fresh PBMCs compared to cryopreserved PBMCs
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
Secondary outcomes:
measure: Assessment of O2 flux in fresh and cryopreserved PBMCs in fasted vs non-fasted sampling conditions
timeFrame: 6 months visit
measure: Assessment of O2 flux in fresh and cryopreserved PBMCs at different seasonal collection time points
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Assessment of O2 flux in fresh and cryopreserved PBMCs at different venipuncture sites
timeFrame: 3 months visit
measure: Assessment of blood count and differential blood count I
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Assessment of blood count and differential blood count II
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Concentration of Creatinine and Urea
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Concentration of Creatine Kinase
timeFrame: Baseline, 6, 12 months visit
measure: Concentration of Glucose
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Concentration of HbA1c
timeFrame: Baseline, 6, 12 months visit
measure: Concentration of Sodium, Potassium, Chloride and Calcium
timeFrame: Baseline, 6, 12 months visit
measure: Concentration of GOT and GPT
timeFrame: Baseline, 6, 12 months visit
measure: Concentration of triglyceride and cholesterol
timeFrame: Baseline, 6, 12 months visit
measure: Concentration of LDL-cholesterol and HDL-cholesterol
timeFrame: Baseline, 6, 12 months visit
measure: Concentration of Lipoprotein a
timeFrame: Baseline visit
measure: Assessment of Sedimentation rate
timeFrame: Baseline, 12 months visit
measure: Concentration of C-reactive protein
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Concentration of Interleukin-6
timeFrame: Baseline, 6, 12 months visit
measure: Concentration of Thyroid-stimulating hormone
timeFrame: Baseline, 12 months visit
measure: Concentration of Iric acid
timeFrame: Baseline, 12 months visit
measure: Concentration of Ferritin
timeFrame: Baseline, 12 months visit
Other outcomes:
measure: Demographic data I
timeFrame: Baseline visit
measure: Demographic data II
timeFrame: Baseline visit
measure: Demographic data III
timeFrame: Baseline visit
measure: Demographic data - Personal background and lifestyle I
timeFrame: Baseline visit
measure: Menstrual cycle duration (women only)
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Menstrual cycle length (women only)
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Demographic data - Personal background and lifestyle II
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Demographic data - Personal background and lifestyle III
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Demographic data - Personal background and lifestyle IV
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Medical History Assessment
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
measure: Assessment of mental well-being using the Hospital Anxiety and Depression Scale - German Version (HADS-D) questionnaire
timeFrame: Baseline visit, 3, 6, 9, 12 months visit
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck - Department of Neurology
state: Tyrol
Study officials:
affiliation: Medical University of Innsbruck
name: Michael Knoflach, AssozProf Dr
role: PRINCIPAL_INVESTIGATOR
References: