Cognitive Frailty and Oxygen-ozone Therapy

NCT06071611 | Completed

• 1 other identifier: RF-2016-02363298
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cognitive Frailty

Outcome Measures

Primary Outcomes (10)

• 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

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

• 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

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

• 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

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

• 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

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

• 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

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

• 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

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

• 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

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

• 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

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

• 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

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

• 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

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

Secondary Outcomes (13)

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

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

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

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

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

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

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

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

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

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

Study Arms (3)

Oxygen-Ozone (O2-O3)

EXPERIMENTAL

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.

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

Oxygen (O2)

ACTIVE COMPARATOR

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

Other: Active Comparator: Oxygen (O2)

Placebo (Air)

PLACEBO COMPARATOR

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

Other: Placebo Comparator: Placebo (Air)

Interventions

Experimental: Oxygen-Ozone (O2-O3) OTHER

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

Oxygen-Ozone (O2-O3)

Active Comparator: Oxygen (O2) OTHER

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

Oxygen (O2)

Placebo Comparator: Placebo (Air) OTHER

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

Placebo (Air)

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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)".

You may not qualify if:

• 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.

Sponsors & Collaborators

• IRCCS Centro San Giovanni di Dio Fatebenefratelli: lead

Study Sites (1)

IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli

Brescia, 25125, Italy

Location

Related Publications (5)

• 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.

  PMID: 31982474 BACKGROUND

• 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.

  PMID: 32810649 BACKGROUND

• 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.

  PMID: 34341712 BACKGROUND

• 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.

  PMID: 35883714 BACKGROUND

• 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.

  PMID: 28652203 BACKGROUND

MeSH Terms

Interventions

Air

Intervention Hierarchy (Ancestors)

Atmosphere; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Meteorological Concepts; Environment and Public Health

Study Officials

• Cristina Geroldi, MD

  IRCCS Centro San Giovanni di Dio Fatebenefratelli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Principal Investigator (CoPI)

Study Record Dates

• First Submitted: September 11, 2023
• First Posted: October 6, 2023
• Study Start: July 2, 2019
• Primary Completion: November 2, 2022
• Study Completion: November 17, 2023
• Last Updated: December 26, 2023

Record last verified: 2023-12

Locations

IT (1)