Cognitive Frailty and Oxygen-ozone Therapy

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Status: Completed

Conditions: Cognitive Frailty

Treatments: Other: Placebo Comparator: Placebo (Air); Other: Active Comparator: Oxygen (O2); Other: Experimental: Oxygen-Ozone (O2-O3)

Study type: Interventional

Funder types: Other

Identifiers

NCT06071611

RF-2016-02363298

Details and patient eligibility

About

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.

Full 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.

Enrollment: 75 patients

Sex: All

Ages: 60 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. subjects between the ages of 60 and 85, referring to the diagnosis of amnesic or non-amnesic cognitive disorder, reported by the subject himself or by family members;
2. MMSE score > 24/30;
3. exclusion of dementia, even in the presence of ascertained Alzheimer's disease detected by the most advanced diagnostic techniques;
4. function intact, or functional reduction not related to the cognitive problem;
5. pharmacological therapy for the treatment of stable cognitive or behavioral disorders for at least 3 months at the time of enrolment;
6. specific assessments/tools for frailty: "Italian frailty index (IFi)" and for "Frailty Instrument (FIt) based on the Survey of Health, Ageing and Retirement in Europe (SHARE-FIt)".

Exclusion criteria

1. subjects affected by disabling vision or hearing impairments;
2. subjects affected by known psychosis or psychiatric illness, alcohol or drug abuse;
3. subjects affected by uncontrolled hyperthyroidism or by Glucose-6-Phostate Dehydrogenase Deficiency (G6PD)-Favism (according to S.I.O.O.T Guidelines, http://www.ossiozono.it);
4. subjects who considered invasive the methodology for rectal insufflation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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75 participants in 3 patient groups, including a placebo group

Oxygen-Ozone (O2-O3)

Experimental group

Description:

A small catheter is inserted into the rectum and a total amount of 150cc of O2-O3 mixture at the concentration of 30ug of O3 per cc of O2 over a 5-10 min period is administered.

Treatment:

Other: Experimental: Oxygen-Ozone (O2-O3)

Oxygen (O2)

Active Comparator group

Description:

A small catheter is inserted into the rectum and a total amount of 150cc of O2 over a 5-10 min period is administered.

Treatment:

Other: Active Comparator: Oxygen (O2)

Placebo (Air)

Placebo Comparator group

Description:

A small catheter is inserted into the rectum and a total amount of 150cc of air over a 5-10 min period is administered.

Treatment:

Other: Placebo Comparator: Placebo (Air)