# Cognitive, Neuropsychological and Biological Effects of Oxygen–Ozone Therapy on Frailty: A Study Protocol for a 5-Week, Randomized, Placebo-Controlled Trial

## TL;DR

This study explores how oxygen-ozone therapy might improve cognitive and biological markers in older individuals with cognitive frailty.

## Contribution

The study introduces a novel randomized, placebo-controlled trial protocol to assess ozone therapy's effects on cognitive frailty.

## Key findings

- The study will evaluate changes in cognitive and neuropsychological scores over time.
- Transcriptomic, proteomic, and metabolomic biomarker changes will be analyzed to understand ozone therapy's biological effects.

## Abstract

Cognitive frailty (CF) is a heterogeneous syndrome that is becoming one of the most serious health problems as the world’s population age is increasing. Elucidating its biological mechanisms as well as prevention and treatments is becoming increasingly significant, particularly in view of the associated health costs. We presented the study protocol of a research project funded by the Italian Ministry of Health (grant number RF-2016-02363298) aiming to investigate the cognitive and neuropsychological effects of a 5-week treatment with therapy based on the regenerative properties of ozone (O3) in a cohort of subjects stratified according to CF scores. We also studied the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons were recruited and randomly assigned to receive the active treatment (150 cc of oxygen-O2-O3 mixture at the concentration of 30 µg of O3 per cc of O2), O2, or the placebo (air) for 5 weeks. The main endpoints were the change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), and 15 (T15) after treatment and the change in biomarker levels resulting from transcriptomics, proteomics, and metabolomic patterns at the same times. The positive results from this study could have important clinical implications.