Plasticizer Exposure and Its Consequences on Health
NCT Number: NCT06512298
Acronym: PEACH
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Beta-thalassemia|Glioma|Healthy Controls|Transfusion-dependent Beta-Thalassemia|Intracranial Hemorrhages|Toxicity
Sponsor: Medical University of Vienna
Collaborators: University of Vienna
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 120
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-10-01
Completion Date: 2027-09-30
Locations: Medical University of Vienna, Vienna, 1090, Austria

Summary:
Plasticizers are chemicals commonly found in many everyday items, from food packaging to medical equipment. Although they are pervasive in our daily lives, researchers still don't have a clear picture of their long-term effects on human health. Evidence suggests that these substances might disrupt various biological functions such as the immune system, the balance of gut bacteria, hormone regulation, and brain processes. While some studies have linked plasticizer exposure to health issues, definitive data from human studies are still lacking.

The PEACH study aims to bridge these knowledge gaps by investigating how plasticizers affect human health. The study focuses on understanding how these chemicals are absorbed, distributed, and accumulated in the body across different groups of patients. The investigators are particularly interested in how plasticizers influence gut microbiota and the functionality of immune cells, as well as their effects on neurotransmitters involved in brain function.

A combination of patient data, systems biology, and laboratory models will be used to thoroughly assess the biological impacts of plasticizers. Advanced techniques such as mass spectrometry will aid in studying toxicokinetic properties, sequencing technologies will be used to examine immune effects, and radiouptake assays will be employed to explore interactions with neurotransmitter transport. This comprehensive methodology will provide new insights into the effects of both short-term and long-term exposure to plasticizers.

The PEACH study introduces innovative methods to the field, aiming to create a robust model for understanding how plasticizer compounds behave in the human body. It employs state-of-the-art techniques to assess the dynamics of these chemicals, marking a significant advancement in environmental health research.

Primary Outcome Measures: Accumulation of plasticizers in transfused patients, Plasticizer concentrations (mmol/L) will be measured from the plasma of thalassemia major patients two weeks after the last pRBC-transfusion and compared to plasma levels of healthy controls of beta-thalassemia intermedia/minor patient using MANCOVA. Age, sex and liver/kidney retention will be taken into account as covariates and Tukey HSD or Scheffe tests used for even and uneven group sizes, respectively., 3 years
Other Outcome Measures: Accumulation of plasticizers during storage in pRBC-bags, Biweekly measurements of blood-bag aliquots will be conducted, and concentrations of \> 30 plasticizer analyzed. 15 of these (main compounds) will be used and subjected to repeated measures ANOVA with within group comparisons. The Sidak correction will be used as a post-hoc test., 1 year|Plasticizer release into the CSF of ICU-patients, The accumulation/release of plasticizers within/into the CSF (mmol/L) will be monitored longitudinally in relation to time (h) using repeated-measures ANCOVA with Sidak correction. Age, sex, as well as liver and kidney function will be considered as covariates., 3 years|Studying the accumulation of plasticizers within the CSF using a cross-sectional design, Accumulation of plasticizers within CSF will be analyzed using MANCOVA, taking age, sex, liver/kidney function as covariates. Thereby, abundancy (mmol/L) of plasticizers within the CNS will be compared between groups., 3 years|Pharmacodynamic analyses (IC50), IC50 (mmol/L) values for neurotransmitter transport at SLC6 transporters will be derived upon co-incubation with plasticizers during the uptake of the transporters cognat substrate to describe the pharmacological profile of plasticizers and their interaction with neurotransmitter transport., 3 years|Pharmacodynamic analyses (Vmax), Vmax values for neurotransmitter transport at SLC6 transporters (pmol/min) will be derived upon co-incubation with plasticizers during the uptake of the transporters cognat substrate to describe the pharmacological profile of plasticizers and their interaction with neurotransmitter transport., 3 years