Cognitive Frailty and Oxygen-ozone Therapy
Condition: Cognitive Frailty
MeSH terms: Frailty
Study type: Interventional

Summary: 
      As the world's population age, frailty is moving to the forefront of health and medical
      research and may become one of the world's most serious health issues. Understanding frailty
      prevention and treatment becomes even more crucial in order to reduce national healthcare
      costs. Oxygen-Ozone (O2-O3) therapy is a no-invasive/no-pharmacological and low cost
      procedure based on the therapeutic effects of low O3 concentrations, already used in medicine
      as an alternative/adjuvant treatment for different diseases and in the elderly. This project
      is the first pilot double blind randomized controlled trial where a group of elderly frail
      subjects are stratified as untreated (air), treated with pure O2 and treated with a mixture
      of O2-O3. The biological corollary will be transcriptomics, proteomics and also cognitive
      impairment assessment at baseline and after treatment. An algorithm combining these data will
      identify biomarkers of the response to O2-O3 therapy.
    

Detailed description: 
      Background: Although frailty does not yet have an internationally recognized standard
      definition, the general premise is that it may be considered a geriatric syndrome reflecting
      multi-system dysfunction, in which individuals are able to dynamically transition between
      severity states. The World Health Organization and The International Association of
      Geriatrics and Gerontology are working on an internationally accepted frailty definition.
      Accumulating evidence supports the existence of a close relation between frailty and
      cognitive impairment in subjects with/without dementia. To date specific treatments for the
      cognitive frailty are not still available. Oxygen-Ozone (O2-O3) therapy is a
      no-invasive/no-pharmacological low cost procedure based on therapeutic effects of low O3
      concentrations and used in medicine as an alternative/adjuvant treatment for different
      diseases and for improving metabolic activities in elderly. Molecular evidence shows that low
      O3 concentrations dissolve in the biological fluids and induce a mild oxidative stress, which
      stimulates antioxidant defences thus preventing the inflammatory response and cell damage.
      Inflammatory processes, altered release of the main reactive O2 species and
      mitochondrial/cytoskeletal modifications have been hypothesized to influence significantly
      the frailty state as well as the neurodevelopmental network on cognitive impairment.

      Aims

        1. To characterize clinical and neuropsychological-cognitive impairment profiles in elderly
           frail subjects at baseline and after treatment.

        2. To identify in vivo peripheral biomarkers associated to O2-O3 therapy through
           transcriptomic and proteomic analyses at baseline and after treatment.

        3. To correlate clinical/cognitive improvement with transcriptomic and proteomic profiles
           to identify biomarkers associated to treatment response.
    

Intervention name(s): Experimental: Oxygen-Ozone (O2-O3); Active Comparator: Oxygen (O2); Placebo Comparator: Placebo (Air)
Intervention type(s): Other; Other; Other
Intervention description(s): Oxygen-Ozone (O2-O3) treatment by rectal insufflations for 5 weeks (3 sessions for week).; Oxygen (O2) treatment by rectal insufflations for 5 weeks (3 sessions for week).; Air treatment by rectal insufflations for 5 weeks (3 sessions for week).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment