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OZOCLO_MUCOSITIS: a New Protocol for Prevention of Oral Mucositis (OZOCLO_MUCOS)

Primary Purpose

Mucositis (MeSH Unique ID: D052016), Stomatitis (MeSH Unique ID: D013280)

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
1. alpha acid lipoic - tables
2. ozonated oil - mouthwash
3. chlorhexidine 0,2% - mouthwash
4. sodium bicarbonate 5% solution - mouthwash
Sponsored by
University of Palermo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Mucositis (MeSH Unique ID: D052016)

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Aged 18-80 years
  • Planned to receive conventional chemotherapy such as:

    • CMF (cyclophosphamide (Endoxan), methotrexate, 5-FU))
    • Standard AC+T regimen (doxorubicin (Adriamycin)), cyclophosphamide (Endoxan), Taxane [paclitaxel (Taxol) or docetaxel (Taxotere)) or any combination of two or more components (e.g., ACT, TAC, TA, AT, AC)
    • ABVD (doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine)
    • FOLFIRI (irinotecan, 5-FU, leucovorin)
    • Any other 5-FU-based regimen
  • Planned to receive at conventional new generation targeted agents (tyrosine-kinase inhibitors or monoclonal antibodies) such as cetuximab, axitinib, bevacizumab, sunitinib, and sorafenib, temsirolimus, everolimus, vemurafenib, dabrafenib.
  • Be willing and able to complete all study-related activities
  • Properly obtained written informed consent

Exclusion Criteria:

  • Receiving any oxaliplatin-containing chemotherapy regimen, such as FOLFOX
  • Concurrent radiotherapy
  • Unable or unwilling to complete study assessments
  • Concurrent participation in another interventional clinical study or use of another investigational agent within 30 days before randomization
  • Any other clinical or psychiatric condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the protocol
  • Chronic use of opioid analgesics

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Placebo Comparator

    Active Comparator

    Active Comparator

    Arm Label

    Group I, OZOCLO

    Group II, OBC

    Group III, CHX

    Group IV, AAL-OZ

    Arm Description

    • Group I, OZOCLO alpha acid lipoic - 600 mg/die per os from 7 days before the beginning of chemotherapy and continue for other 4 days ozonated oil - mouthwash (1 minute- three times/die after oral hygiene, possibly) from the beginning of chemotherapy and for 2 weeks chlorhexidine 0,2% - mouthwash (1 minute- three times/die after oral hygiene, possibly) from five days after the beginning of chemotherapy and for subsequent 2 weeks

    • Group II, OBC Sodium bicarbonate 5% solution - mouthwash (1 minute- three times/die after oral hygiene, possibly) from the beginning of chemotherapy and for 3 weeks

    • Group III, CHX Chlorhexidine 0,2% - mouthwash (1 minute- three times/die after oral hygiene, possibly) from five days after the beginning of chemotherapy and for subsequent 2 weeks

    • Group IV, AAL-OZ alpha acid lipoic - 600 mg/die per os from 7 days before the beginning of chemotherapy and continue for other 4 days ozonated oil - mouthwash (1 minute- three times/die after oral hygiene, possibly) from the beginning of chemotherapy and for 2 weeks

    Outcomes

    Primary Outcome Measures

    Change of OM incidence
    In order to demonstrate whether the new protocol OZOCLO determines change of the incidence of OM compared to sodium bicarbonate solution (OBC) or chlorhexidine (CHX) mouthwash alone or the binomial AAL-OZ combination, in patients treated with chemotherapy regimens.

    Secondary Outcome Measures

    Delay onset of OM
    In order to determine whether the new protocol OZOCLO determines a delay of onset for OM, considering that it currently begins at 7th day, compared to sodium bicarbonate solution (OBC) or chlorhexidine (CHX) mouthwash alone or a binomial administration of systemic alpha-lipoic acid and topical ozonated oil.

    Full Information

    First Posted
    December 14, 2021
    Last Updated
    January 26, 2022
    Sponsor
    University of Palermo
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05211622
    Brief Title
    OZOCLO_MUCOSITIS: a New Protocol for Prevention of Oral Mucositis
    Acronym
    OZOCLO_MUCOS
    Official Title
    OZOCLO: a Randomized Clinical Trial for Prevention of Oral Mucositis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 10, 2022 (Anticipated)
    Primary Completion Date
    December 31, 2022 (Anticipated)
    Study Completion Date
    January 10, 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Palermo

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Oral mucositis (OM) is a significant side effect of cytotoxic anti-cancer chemotherapy and HN radiotherapy. CT-associated OM (CT-OM). It is the ulcerative phase that is most painful and associated with poor health outcomes. The sequelae of CT-OM, which include pain, odyno/dys-phagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions, and discontinuations that not only negatively impact the quality of life but also tumor control and survivorship. To date, OM management is aimed to control symptoms through topical or systemic analgesics and topical application of barrier agents to cover injured mucosa as a salve or ointment. According to the recent MASCC/ISOO Clinical Practice Guidelines for the Management of Mucositis Secondary to Cancer Therapy, no guideline was possible regarding the use of saline or sodium bicarbonate rinses in the prevention or treatment of OM-CT in patients undergoing cancer therapy because of limited data. Ozone at low medical concentration, not included in MASCC guidelines, will be generally proven to induce a mild activation of protective anti-oxidant pathways, thus exerting therapeutic effects in many inflammatory diseases. Aim: to evaluate the effectiveness of a new protocol OZOCLO (alpha-lipoic acid, ozonated oil, and chlorhexidine [CHX] mouthwash) compared to sodium bicarbonate solution (Oral Basic Care- OBC) or chlorhexidine (CHX) mouthwash alone or to a binomial administration (AAL-OZ) of systemic alpha-lipoic acid and topical ozonated oil to reduce the incidence of OM (primary aim) and/or to postpone the beginning of oral mucositis (OM) and to reduce OM severity (secondary aims).
    Detailed Description
    Oral mucositis (OM) is a significant side effect of cytotoxic anti-cancer chemotherapy and HN radiotherapy. CT-associated OM (CT-OM) begins in the submucosa and becomes clinically on the surface about 4 days after infusion: typical primary manifestations are erythema, mucosal atrophy, and sensitivity. The process continues to deteriorate mucosae, and ulceration occurs a few days later, peaking at 2 weeks and persisting for 1-2 weeks after which it typically resolves spontaneously. It is the ulcerative phase that is most painful and associated with poor health outcomes. The sequelae of CT-OM, which include pain, odyno/dys-phagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions, and discontinuations that not only negatively impact the quality of life but also tumor control and survivorship. To date, OM management is aimed to control symptoms through topical or systemic analgesics and topical application of barrier agents to cover injured mucosa as a salve or ointment. Although the investigators reviewed a large body of evidence, there are still, clinical settings for which there is no recommended intervention. According to the recent MASCC/ISOO Clinical Practice Guidelines for the Management of Mucositis Secondary to Cancer Therapy, no guideline was possible regarding the use of saline or sodium bicarbonate rinses in the prevention or treatment of OM-CT in patients undergoing cancer therapy because of limited data. Despite the limited data available for both saline and sodium bicarbonate, the panel recognizes that these are inert, bland rinses that increase oral clearance, which may help maintain oral hygiene and improve patient comfort. Also, CHX is indicated because of concurrent oral infection and OM, it is acceptable to use it for the oral infection. Ozone at low medical concentration, not included in MASCC guidelines, will be generally proven to induce a mild activation of protective anti-oxidant pathways, thus exerting therapeutic effects in many inflammatory diseases. Aim: to evaluate the effectiveness of a new protocol OZOCLO (alpha-lipoic acid, ozonated oil, and chlorhexidine [CHX] mouthwash) compared to sodium bicarbonate solution (Oral Basic Care- OBC) or chlorhexidine (CHX) mouthwash alone or to a binomial administration (AAL-OZ) of systemic alpha-lipoic acid and topical ozonated oil to reduce the incidence of OM (primary aim) and/or to postpone the beginning of oral mucositis (OM) and to reduce OM severity (secondary aims).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Mucositis (MeSH Unique ID: D052016), Stomatitis (MeSH Unique ID: D013280)

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 4
    Interventional Study Model
    Factorial Assignment
    Model Description
    Patients will be randomly using a table of random numbers (allocation ratio 1:1:1:1). Arm I, OZOCLO alpha acid lipoic - 600 mg/die per os from 7 days before the beginning of chemotherapy and for other 4 die ozonated oil - mouthwash (1 minute- three times/die) for 2 weeks chlorhexidine 0,2% - mouthwash (1 minute- three times/die) from five days after the beginning and for other 2 weeks Arm II, OBC Sodium bicarbonate 5% solution - mouthwash (1 minute- three times/die) for 3 weeks Arm III, CHX Chlorhexidine 0,2% - mouthwash (1 minute- three times/die) from five days after the beginning and for other 2 weeks Arm IV, AAL-OZ alpha acid lipoic - 600 mg/die per os from 7 days before the beginning and continue for other 4 die ozonated oil - mouthwash (1 minute- three times/die) from the beginning and for 2 weeks Every interventional arm will be conducted by the patient at home according to indications and will monitored at 8th, 15th, and the 21st day
    Masking
    ParticipantInvestigator
    Masking Description
    Nobody else
    Allocation
    Randomized
    Enrollment
    80 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Group I, OZOCLO
    Arm Type
    Experimental
    Arm Description
    • Group I, OZOCLO alpha acid lipoic - 600 mg/die per os from 7 days before the beginning of chemotherapy and continue for other 4 days ozonated oil - mouthwash (1 minute- three times/die after oral hygiene, possibly) from the beginning of chemotherapy and for 2 weeks chlorhexidine 0,2% - mouthwash (1 minute- three times/die after oral hygiene, possibly) from five days after the beginning of chemotherapy and for subsequent 2 weeks
    Arm Title
    Group II, OBC
    Arm Type
    Placebo Comparator
    Arm Description
    • Group II, OBC Sodium bicarbonate 5% solution - mouthwash (1 minute- three times/die after oral hygiene, possibly) from the beginning of chemotherapy and for 3 weeks
    Arm Title
    Group III, CHX
    Arm Type
    Active Comparator
    Arm Description
    • Group III, CHX Chlorhexidine 0,2% - mouthwash (1 minute- three times/die after oral hygiene, possibly) from five days after the beginning of chemotherapy and for subsequent 2 weeks
    Arm Title
    Group IV, AAL-OZ
    Arm Type
    Active Comparator
    Arm Description
    • Group IV, AAL-OZ alpha acid lipoic - 600 mg/die per os from 7 days before the beginning of chemotherapy and continue for other 4 days ozonated oil - mouthwash (1 minute- three times/die after oral hygiene, possibly) from the beginning of chemotherapy and for 2 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    1. alpha acid lipoic - tables
    Other Intervention Name(s)
    alpha acid lipoic - tables
    Intervention Description
    600 mg/die per os from 7 days before the beginning of chemotherapy and continue for other 4 days
    Intervention Type
    Drug
    Intervention Name(s)
    2. ozonated oil - mouthwash
    Other Intervention Name(s)
    ozonated oil - mouthwash
    Intervention Description
    1 minute- three times/die after oral hygiene, possibly, from the beginning of chemotherapy and for 2 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    3. chlorhexidine 0,2% - mouthwash
    Other Intervention Name(s)
    chlorhexidine 0,2% - mouthwash
    Intervention Description
    1 minute- three times/die after oral hygiene, possibly, from five days after the beginning of chemotherapy and for subsequent 2 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    4. sodium bicarbonate 5% solution - mouthwash
    Other Intervention Name(s)
    sodium bicarbonate 5% solution - mouthwash
    Intervention Description
    1 minute- three times/die after oral hygiene, possibly, from the beginning of chemotherapy and for 3 weeks
    Primary Outcome Measure Information:
    Title
    Change of OM incidence
    Description
    In order to demonstrate whether the new protocol OZOCLO determines change of the incidence of OM compared to sodium bicarbonate solution (OBC) or chlorhexidine (CHX) mouthwash alone or the binomial AAL-OZ combination, in patients treated with chemotherapy regimens.
    Time Frame
    7th, 14th, and the 21st day after application of the interventions
    Secondary Outcome Measure Information:
    Title
    Delay onset of OM
    Description
    In order to determine whether the new protocol OZOCLO determines a delay of onset for OM, considering that it currently begins at 7th day, compared to sodium bicarbonate solution (OBC) or chlorhexidine (CHX) mouthwash alone or a binomial administration of systemic alpha-lipoic acid and topical ozonated oil.
    Time Frame
    7th, 14th, and the 21st day after application of the interventions
    Other Pre-specified Outcome Measures:
    Title
    OM severity assessment
    Description
    To reduce OM severity, assuming one-point score difference (assessed through the Oral Mucositis World Health Organization Toxicity Scale- from grade 0 - none to grade IV- Oral alimentation impossible) compared to chlorhexidine (CHX) mouthwash alone or a binomial administration of systemic alpha-lipoic acid and topical ozonated oil and two-point score difference compared to sodium bicarbonate solution at one year.
    Time Frame
    7th, 14th, and the 21st day after application of the interventions

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Aged 18-80 years Planned to receive conventional chemotherapy such as: CMF (cyclophosphamide (Endoxan), methotrexate, 5-FU)) Standard AC+T regimen (doxorubicin (Adriamycin)), cyclophosphamide (Endoxan), Taxane [paclitaxel (Taxol) or docetaxel (Taxotere)) or any combination of two or more components (e.g., ACT, TAC, TA, AT, AC) ABVD (doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine) FOLFIRI (irinotecan, 5-FU, leucovorin) Any other 5-FU-based regimen Planned to receive at conventional new generation targeted agents (tyrosine-kinase inhibitors or monoclonal antibodies) such as cetuximab, axitinib, bevacizumab, sunitinib, and sorafenib, temsirolimus, everolimus, vemurafenib, dabrafenib. Be willing and able to complete all study-related activities Properly obtained written informed consent Exclusion Criteria: Receiving any oxaliplatin-containing chemotherapy regimen, such as FOLFOX Concurrent radiotherapy Unable or unwilling to complete study assessments Concurrent participation in another interventional clinical study or use of another investigational agent within 30 days before randomization Any other clinical or psychiatric condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the protocol Chronic use of opioid analgesics
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Olga Di Fede, Professor
    Phone
    +39 3294030298
    Email
    olga.difede@unipa.it
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Olga Di Fede, Professor
    Organizational Affiliation
    University of Palermo, Di.Chir.On.S
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided
    Citations:
    PubMed Identifier
    32786044
    Citation
    Elad S, Cheng KKF, Lalla RV, Yarom N, Hong C, Logan RM, Bowen J, Gibson R, Saunders DP, Zadik Y, Ariyawardana A, Correa ME, Ranna V, Bossi P; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020 Oct 1;126(19):4423-4431. doi: 10.1002/cncr.33100. Epub 2020 Jul 28. Erratum In: Cancer. 2021 Oct 1;127(19):3700.
    Results Reference
    result
    PubMed Identifier
    28075506
    Citation
    Cardona A, Balouch A, Abdul MM, Sedghizadeh PP, Enciso R. Efficacy of chlorhexidine for the prevention and treatment of oral mucositis in cancer patients: a systematic review with meta-analyses. J Oral Pathol Med. 2017 Oct;46(9):680-688. doi: 10.1111/jop.12549. Epub 2017 Feb 8.
    Results Reference
    result
    PubMed Identifier
    2179802
    Citation
    Ferretti GA, Raybould TP, Brown AT, Macdonald JS, Greenwood M, Maruyama Y, Geil J, Lillich TT, Ash RC. Chlorhexidine prophylaxis for chemotherapy- and radiotherapy-induced stomatitis: a randomized double-blind trial. Oral Surg Oral Med Oral Pathol. 1990 Mar;69(3):331-8. doi: 10.1016/0030-4220(90)90295-4.
    Results Reference
    result

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    OZOCLO_MUCOSITIS: a New Protocol for Prevention of Oral Mucositis

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