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Cognitive FrailtyNCT06071611

Cognitive Frailty and Oxygen-ozone Therapy

A study testing Experimental: Oxygen-Ozone (O2-O3) and Active Comparator: Oxygen (O2) in people with Cognitive Frailty, run by IRCCS Centro San Giovanni di Dio Fatebenefratelli at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 60 to 85 years
Conditions the study is for
Cognitive Frailty
What is being tested?
Experimental: Oxygen-Ozone (O2-O3) and Active Comparator: Oxygen (O2)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
75 participants
Where
1 siteItaly
Study dates
2 Jul 2019to 17 Nov 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
  • MMSE score > 24/30;
  • exclusion of dementia, even in the presence of ascertained Alzheimer's disease detected by the most advanced diagnostic techniques;
  • function intact, or functional reduction not related to the cognitive problem;
  • pharmacological therapy for the treatment of stable cognitive or behavioral disorders for at least 3 months at the time of enrolment;
  • 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)".

Who cannot join

  • subjects affected by disabling vision or hearing impairments;
  • subjects affected by known psychosis or psychiatric illness, alcohol or drug abuse;
  • 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);
  • subjects who considered invasive the methodology for rectal insufflation.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli

    Brescia, 25125

Other trials in Italy

About this study

Official title: Cognitive Frailty and Oxygen-ozone Therapy: Integrated Approach to Identify Biological and Neuropsychological Markers

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.

Read the 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.
Being tested
Experimental: Oxygen-Ozone (O2-O3), Active Comparator: Oxygen (O2), Placebo Comparator: Placebo (Air)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Oxygen-Ozone (O2-O3) treatment by rectal insufflations for 5 weeks (3 sessions for week).

  • Active Comparator: Oxygen (O2)Other

    Oxygen (O2) treatment by rectal insufflations for 5 weeks (3 sessions for week).

  • Placebo Comparator: Placebo (Air)Other

    Air treatment by rectal insufflations for 5 weeks (3 sessions for week).

Study groups in NCT06071611
Study groupRoleWhat they receive
Oxygen-Ozone (O2-O3)ExperimentalA 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.
Receives: Other: Experimental: Oxygen-Ozone (O2-O3)
Oxygen (O2)Active comparatorA small catheter is inserted into the rectum and a total amount of 150cc of O2 over a 5-10 min period is administered.
Receives: Other: Active Comparator: Oxygen (O2)
Placebo (Air)Placebo comparatorA small catheter is inserted into the rectum and a total amount of 150cc of air over a 5-10 min period is administered.
Receives: Other: Placebo Comparator: Placebo (Air)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline and post-intervention in Italian frailty index (IFi)

    Italian frailty index (IFi) is an Italian version of the "frailty index" based on accumulation of age-related deficits. IFi has been expressed as a ratio of deficits present/deficits considered after a comprehensive geriatric assessment.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  2. Change from baseline and post-intervention in Frailty Instrument (FIt) based on the Survey of Health, Ageing and Retirement in Europe (SHARE-FIt)

    SHARE-FIt is based on 5-item (i.e. grip strength and four self-reported items: fatigue, loss of appetite and/or eating less than usual, difficulties climbing stairs and/or walking 100 metres, and low level of physical activity). For each gender, a discreet factor (DFactor) model was estimated based on the five SHARE frailty variables.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  3. Change from baseline and post-intervention in Everyday Memory Questionnaire (EMQ)

    Everyday Memory Questionnaire (EMQ) is a subjective measure of memory failure in everyday life, lower scores indicating better memory function.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  4. Change from baseline and post-intervention in Raven's Progressive Matrices (RPM)

    Raven's Progressive Matrices (RPM) is used to measure fluid intelligence, with higher scores indicating better function.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  5. Change from baseline and post-intervention in Free and Cued Selective Reminding Test (FCSRT)

    Free and Cued Selective Reminding Test (FCSRT) is a test used to assess episodic memory, with higher scores indicating better function.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  6. Change from baseline and post-intervention in Rey-Osterrieth Complex Figure A Test (ROCF-A)

    ROCF-A is used to explore visuo-constructional ability and visuo-spatial memory, with higher scores indicating better function.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  7. Change from baseline and post-intervention in Face-name association task (FNAT)

    FNAT is used to assess the patient's associative memory and is composed of encoding and retrieval phases, with higher scores indicating better function.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  8. Change from baseline and post-intervention in Picture naming task (PNT)

    The PNT is designed to explore lexical access, with higher scores indicating better function.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  9. Change from baseline and post-intervention in Trail Making Tests A (TMT-A)

    Trail Making Tests A (TMT-A) is used to assess visual attention and motor speed skills, with lower scores indicating better attention.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  10. Change from baseline and post-intervention in Trail Making Tests B (TMT-B)

    Trail Making Tests B (TMT-B) is used to assess executive functions, with lower scores indicating good performance in executive function.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

Secondary outcomes (13)

  1. Change from baseline and post-intervention in peripheral mRNAs levels in subjects stratified according to IFi or SHARE-FIt scores

    The mRNAs peripheral signatures compared before and after treatments. To identify the list of differentially expressed mRNAs we filter ANOVA results using both fold change |FC| ≥ 1.5 and p-value ≤0.05.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  2. Change from baseline and post-intervention in peripheral NGFb (beta-Nerve Growth Factor) levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of NGFb compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  3. Change from baseline and post-intervention in peripheral BDNF (Brain Derived Neurotrophic Factor) levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of BDNF compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  4. Change from baseline and post-intervention in peripheral VEGF (Vascular Endothelial Growth Factor) levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of VEGF compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  5. Change from baseline and post-intervention in peripheral IL, Interleukin-1b levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of IL-1b compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  6. Change from baseline and post-intervention in peripheral IL, Interleukin-4 levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of IL-4 compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  7. Change from baseline and post-intervention in peripheral IL, Interleukin-6 levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of IL-6 compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  8. Change from baseline and post-intervention in peripheral IL, Interleukin-8 levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of IL-8 compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  9. Change from baseline and post-intervention in peripheral IL, Interleukin-9 levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of IL-9 compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  10. Change from baseline and post-intervention in peripheral IL, Interleukin-10 levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of IL-10 compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  11. Change from baseline and post-intervention in peripheral IL, Interleukin-13 levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of IL-13 compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  12. Change from baseline and post-intervention in peripheral TNF-a (Tumor Necrosis Factor) levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of TNF-a compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

  13. Change from baseline and post-intervention in peripheral IFN-g (Interferon-gamma) levels in subjects stratified according to IFi or SHARE-FIt scores

    Peripheral concentrations (pg/ml) of IFN-g compared before and after treatments.

    Change = month 3rd after treatment - baseline score / Change = month 9th after treatment - baseline score / Change = month 15th after treatment - baseline score

    Measured: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2023
  2. Study start2 Jul 2019
  3. Primary completion2 Nov 2022
  4. Study completion17 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06071611
Sponsor's protocol ID
RF-2016-02363298
Status last verified
Dec 2023
First submitted
11 Sep 2023
Last updated
26 Dec 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Scassellati C, Ciani M, Galoforo AC, Zanardini R, Bonvicini C, Geroldi C. Molecular mechanisms in cognitive frailty: potential therapeutic targets for oxygen-ozone treatment. Mech Ageing Dev. 2020 Mar;186:111210. doi: 10.1016/j.mad.2020.111210. Epub 2020 Jan 23.

    PubMed 31982474

  • Scassellati C, Galoforo AC, Bonvicini C, Esposito C, Ricevuti G. Ozone: a natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders. Ageing Res Rev. 2020 Nov;63:101138. doi: 10.1016/j.arr.2020.101138. Epub 2020 Aug 15.

    PubMed 32810649

  • Scassellati C, Galoforo AC, Esposito C, Ciani M, Ricevuti G, Bonvicini C. Promising Intervention Approaches to Potentially Resolve Neuroinflammation And Steroid Hormones Alterations in Alzheimer's Disease and Its Neuropsychiatric Symptoms. Aging Dis. 2021 Aug 1;12(5):1337-1357. doi: 10.14336/AD.2021.0122. eCollection 2021 Aug.

    PubMed 34341712

  • Varesi A, Chirumbolo S, Campagnoli LIM, Pierella E, Piccini GB, Carrara A, Ricevuti G, Scassellati C, Bonvicini C, Pascale A. The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence. Antioxidants (Basel). 2022 Jun 22;11(7):1224. doi: 10.3390/antiox11071224.

    PubMed 35883714

  • Scassellati C, Costanzo M, Cisterna B, Nodari A, Galie M, Cattaneo A, Covi V, Tabaracci G, Bonvicini C, Malatesta M. Effects of mild ozonisation on gene expression and nuclear domains organization in vitro. Toxicol In Vitro. 2017 Oct;44:100-110. doi: 10.1016/j.tiv.2017.06.021. Epub 2017 Jun 23.

    PubMed 28652203

Questions about this trial

What is this clinical trial studying?

A study testing Experimental: Oxygen-Ozone (O2-O3) and Active Comparator: Oxygen (O2) in people with Cognitive Frailty, run by IRCCS Centro San Giovanni di Dio Fatebenefratelli at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline and post-intervention in Italian frailty index (IFi) (time frame: Baseline (pre-intervention), post-intervention (3, 9 and 15 months)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06071611, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2023.

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