MEDICATION RELATED OSTEONECROSIS OF THE JAWPhase 1/2OZOPROMAFNCT05036837
Infiltration of Medical Ozone for the Treatment of Medication-Related Osteonecrosis of the Jaws (MRONJ)
A Phase 1/2 study testing OZOPROMAF_SEQ1 in people with MEDICATION RELATED OSTEONECROSIS OF THE JAW, run by University of Palermo at 1 site in Italy.
Trial summary
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is also a potentially painful and debilitating condition. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- MEDICATION RELATED OSTEONECROSIS OF THE JAW
- What is being tested?
- OZOPROMAF_SEQ1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 1 Feb 2018to 1 Mar 2022
- Phase
- Phase 1/2
- 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 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Clinical and radiological diagnosis of MRONJ
- Patients with MRONJ non-eligibilible to the standard treatment (medical or surgical alone) for unstable systemic conditions or for unaccepted consent due.
Who cannot join
- Head and neck radiotherapy
- Long term sistemic antimicrobial therapy
Trial locations and contacts
1 site in 1 country.
Italy1 site
Azienda Ospedaliera Universitaria Policlinico "P. Giaccone" Palermo - University of Palermo
Palermo, Italy - Sicily, 90127
About this study
Official title: OZOPROMAF: Validation Study of the Use of Ozonotherapy in Mronj Management- Protocol of Ozone by Infiltrations in Patients With Osteonecrosis of the Jaws Drug Related
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is also a potentially painful and debilitating condition. Today, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established.
Among non-invasive procedures to treat MRONJ, the use of medical ozone (O3) arises for its properties and has been deployed and evaluated. O3 has generally proven to play a role in the treatment of chronic, nonhealing, or ischemic wounds, due to its antimicrobial and anti-oxidant properties and to bio-stimulation; it has been extensively used for different medical approaches and purposes. In oral cavity, local applications are carried out by ozonized water (i.e. spray or compress) or gel.
Read more
The aim of this open trial is to assess the efficacy and the safety of O3 by a new method of application, i.e. infiltrations of oral mucosa, in patients with a diagnosis of MRONJ, which are non-eligible for the standard of care, regardless staging.
All cases included in our study are MRONJ and staged according to the classification of the Italian Societies of Oral Medicine and Maxillofacial Surgery (the SICMF/SIPMO staging system); in addition, they arereported to AIFA, the Italian Medicines Agency, for registration of the adverse event drug related.Patients included in our study are selected due to their non-eligibility to the standard treatment (conservative/medical for long term or surgical alone) for unstable systemic conditions or unaccepted consent due to extensive proposed approach due to the advanced disease.
During the first examination (T0), medical, pharmacological, and dental history of patients are recorded. Data collected are: (1) age; (2) gender; (3) indications for use, type, cumulative dose and duration of MRONJ-related drugs; (4); history of chemotherapy; (5) other medications; (6) other diseases; (7) smoking.
For every patient, Cone Beam CT dental scan or maxillofacial CT scan has performed for staging at T0 and 12 (T4) months after; orthopantomograph has performed during protocol (T3). The main CT features evaluated and associated to MRONJ presence and healing are as follows: a) bone sclerosis, b) depth of lesion; c) formation of sequestrum.
When more than one MRONJ lesion are present, the protocol is applied one by one.
Read the detailed description
OZOPROMAF protocol consists of: local superficial anesthesia by application of EMLA® cream, intra-tissue injection of a 15 ml OxigenOzone (O2O3) mixture by 26Gx 1⁄2 - 0.45x13mm needle into the mucosal margin surrounding the bone exposure or around the situs already evidenced by CT scan.
Moreover, pain intensity is assessed at each visit by means of a questionnaire for pain and/or other symptoms evaluation before and after the protocol, based on numerical rating scale (NRS).
OZOPROMAF is applied on 7-15 days, depending on the patient compliance, until the resolution, identified as formation of sequestrum and clinical healing (T1).
The day after the procedure, every patient iss supported by phone evaluating pain and/or adverse events with a questionnaire In case of unavailability of the patient for the weekly treatment, it is mandatory the phone call for the questionnaire, in order to evaluate symptoms by simple questions and NAS scale.
After resolution (T1), follow-up visits are scheduled to confirm the healing of MRONJ at 1 (T2), 3, 6 (T3), 12 (T4), 18- 24 months (T5). Radiographic evaluations of bone healing are scheduled at T3 and T4.
Positive outcomes for the OZOPROMAF protocol are evaluated at T1 as no clinical signs of acute phlogosis and no symptoms compatible with MRONJ; at T5 as clinical healing and no radiological signs of MRONJ.
- Being tested
- OZOPROMAF_SEQ1
- Keywords
- MRONJ, Osteonecrosis, Jaw, Antiresorptive, Antiangiogenic drugs, Adverse event
- Medical subject headings
- Osteonecrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OZOPROMAF_SEQ1Drug
OZOPROMAF protocol consists of: local superficial anesthesia by EMLA® cream, intra-tissue injection of a 15 ml OxigenOzone (mixture by 26Gx 1⁄2 - 0.45x13mm needle into the mucosal margin surrounding the bone exposure or around the situs already evidenced by CT scan. It is applied on 7-15 days, depending on the patient compliance, until the formation of sequestrum and clinical healing (T1).
Pain intensity is assessed by means of a questionnaire for pain and/or other symptoms evaluation before and after the protocol, based on numerical rating scale (NRS).
After resolution (T1), follow-up visits are scheduled to confirm the healing of MRONJ at 1 (T2), 3, 6 (T3), 12 (T4), 18- 24 months (T5).
Radiographic evaluations of bone healing are scheduled at T3 and T4.
Positive outcomes for the OZOPROMAF protocol are evaluated at T1 as no clinical signs of acute phlogosis and no symptoms compatible with MRONJ; at T5 as clinical healing and no radiological signs of MRONJ.
| Study group | Role | What they receive |
|---|---|---|
| OZOPROMAF_SEQ1 | Experimental | OZOPROMAF consists of: local superficial anesthesia by application of EMLA® cream, intra-tissue injection of a 15 ml OxigenOzone (O2O3) mixture by 26Gx 1⁄2 - 0.45x13mm needle into mucosal margin surrounding bone exposure or around situs evidenced by CT scans.
Pain intensity and/or other symptoms are assessed at each visit and the day after by a questionnaire (numerical rating scale).
OZOPROMAF is applied on 7-15 days, depending on patient compliance, until the resolution (i.e. formation of sequestrum and clinical healing -T1).
Follow-up visits are scheduled to confirm healing at 1 (T2), 3, 6 (T3), 12 (T4), 18- 24 months (T5). Radiographic evaluations of bone healing are scheduled at T3/ T4/T5.
Positive outcomes
at T1/T2 clinical healing (no signs of acute phlogosis and no symptoms compatible with MRONJ);
at T3/ T4/T5 clinical healing and no radiological signs of MRONJ. Receives: Drug: OZOPROMAF_SEQ1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
MUCOSAL HEALING
no clinical signs and no symptoms compatible with MRONJ outcome measure:
- formation of sequestrum by visualization of bone sequestrum
- no infectius signs by visual inspection
- no pain by NAS
Measured: 3 months
MUCOSAL HEALING (1-T2)
no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection
Measured: 3 months (T2)
MUCOSAL HEALING (2-T2)
no symptoms Outcome measure: pain evaluation by NAS
Measured: 3 months (T2)
BONE HEALING (T2)
Outcome measure: no radiological signs compatible with MRONJ by OPT (orthopantomograph)
Measured: 3 months (T2)
MUCOSAL HEALING (1-T3)
no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection
Measured: 6 months (T3)
MUCOSAL HEALING (2-T3)
no symptoms Outcome measure:pain evaluation by NAS
Measured: 6 months (T3)
BONE HEALING (T3)
Outcome measure: no radiological signs compatible with MRONJ by CT (computed tomography)
Measured: 6 months (T3)
MUCOSAL HEALING (1-T4)
no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection
Measured: 12 months (T4)
MUCOSAL HEALING (2-T4)
no symptoms Outcome measure:pain evaluation by NAS
Measured: 12 months (T4)
BONE HEALING (T4)
Outcome measure:
no radiological signs compatible with MRONJ by CT (computed tomography)
Measured: 12 months (T4)
MUCOSAL HEALING (1-T5)
no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection
Measured: 18-24 months (T5)
MUCOSAL HEALING (2-T5)
no symptoms Outcome measure: pain evaluation by NAS
Measured: 18-24 months (T5)
BONE HEALING (T5)
Outcome measure:
no radiological signs compatible with MRONJ by CT (computed tomography)
Measured: 18-24 months (T5)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2021
- Study start1 Feb 2018
- Primary completion1 Mar 2020
- Study completion1 Mar 2022 (estimated)
Why it stopped: DUE TO PANDEMIC CONDITIONS
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MEDICATION RELATED OSTEONECROSIS OF THE JAWStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Palermo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Olga Di Fede, University of Palermo
- Investigators
- Olga Di Fede, Professor, Principal investigator, University of Palermo - Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05036837
- Sponsor's protocol ID
- OZOPROMAF_SEQ1
- Acronym
- OZOPROMAF
- Status last verified
- Sep 2021
- First submitted
- 16 Jun 2021
- Last updated
- 8 Sep 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Patients included in our study are selected due to their non-eligibility to the standard treatment (conservative/medical for long term or surgical alone) for unstable systemic conditions or unaccepted consent due to extensive proposed approach due to the advanced disease.
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OZOPROMAF: Validation Study of the Use of Ozonotherapy in Mronj Management- Protocol of Ozone by Infiltrations in Patients With Osteonecrosis of the Jaws Drug Related
- ClinicalTrials.gov ID
- NCT05036837
- Acronym / sponsor ID
- OZOPROMAF / OZOPROMAF_SEQ1
- Keywords
- MRONJ, Osteonecrosis, Jaw, Antiresorptive, Antiangiogenic drugs, Adverse event
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: DUE TO PANDEMIC CONDITIONS
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of PalermoUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 1 Mar 2020 (actual)
- Study completion
- 1 Mar 2022 (estimated)
- First posted
- 8 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is also a potentially painful and debilitating condition. Today, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established.
Among non-invasive procedures to treat MRONJ, the use of medical ozone (O3) arises for its properties and has been deployed and evaluated. O3 has generally proven to play a role in the treatment of chronic, nonhealing, or ischemic wounds, due to its antimicrobial and anti-oxidant properties and to bio-stimulation; it has been extensively used for different medical approaches and purposes. In oral cavity, local applications are carried out by ozonized water (i.e. spray or compress) or gel.
The aim of this open trial is to assess the efficacy and the safety of O3 by a new method of application, i.e. infiltrations of oral mucosa, in patients with a diagnosis of MRONJ, which are non-eligible for the standard of care, regardless staging.
All cases included in our study are MRONJ and staged according to the classification of the Italian Societies of Oral Medicine and Maxillofacial Surgery (the SICMF/SIPMO staging system); in addition, they arereported to AIFA, the Italian Medicines Agency, for registration of the adverse event drug related.Patients included in our study are selected due to their non-eligibility to the standard treatment (conservative/medical for long term or surgical alone) for unstable systemic conditions or unaccepted consent due to extensive proposed approach due to the advanced disease.
During the first examination (T0), medical, pharmacological, and dental history of patients are recorded. Data collected are: (1) age; (2) gender; (3) indications for use, type, cumulative dose and duration of MRONJ-related drugs; (4); history of chemotherapy; (5) other medications; (6) other diseases; (7) smoking.
For every patient, Cone Beam CT dental scan or maxillofacial CT scan has performed for staging at T0 and 12 (T4) months after; orthopantomograph has performed during protocol (T3). The main CT features evaluated and associated to MRONJ presence and healing are as follows: a) bone sclerosis, b) depth of lesion; c) formation of sequestrum.
When more than one MRONJ lesion are present, the protocol is applied one by one.
Detailed description
OZOPROMAF protocol consists of: local superficial anesthesia by application of EMLA® cream, intra-tissue injection of a 15 ml OxigenOzone (O2O3) mixture by 26Gx 1⁄2 - 0.45x13mm needle into the mucosal margin surrounding the bone exposure or around the situs already evidenced by CT scan.
Moreover, pain intensity is assessed at each visit by means of a questionnaire for pain and/or other symptoms evaluation before and after the protocol, based on numerical rating scale (NRS).
OZOPROMAF is applied on 7-15 days, depending on the patient compliance, until the resolution, identified as formation of sequestrum and clinical healing (T1).
The day after the procedure, every patient iss supported by phone evaluating pain and/or adverse events with a questionnaire In case of unavailability of the patient for the weekly treatment, it is mandatory the phone call for the questionnaire, in order to evaluate symptoms by simple questions and NAS scale.
After resolution (T1), follow-up visits are scheduled to confirm the healing of MRONJ at 1 (T2), 3, 6 (T3), 12 (T4), 18- 24 months (T5). Radiographic evaluations of bone healing are scheduled at T3 and T4.
Positive outcomes for the OZOPROMAF protocol are evaluated at T1 as no clinical signs of acute phlogosis and no symptoms compatible with MRONJ; at T5 as clinical healing and no radiological signs of MRONJ.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OZOPROMAF_SEQ1 | Experimental | Drug: OZOPROMAF_SEQ1OZOPROMAF consists of: local superficial anesthesia by application of EMLA® cream, intra-tissue injection of a 15 ml OxigenOzone (O2O3) mixture by 26Gx 1⁄2 - 0.45x13mm needle into mucosal margin surrounding bone exposure or around situs evidenced by CT scans. Pain intensity and/or other symptoms are assessed at each visit and the day after by a questionnaire (numerical rating scale). OZOPROMAF is applied on 7-15 days, depending on patient compliance, until the resolution (i.e. formation of sequestrum and clinical healing -T1). Follow-up visits are scheduled to confirm healing at 1 (T2), 3, 6 (T3), 12 (T4), 18- 24 months (T5). Radiographic evaluations of bone healing are scheduled at T3/ T4/T5. Positive outcomes at T1/T2 clinical healing (no signs of acute phlogosis and no symptoms compatible with MRONJ); at T3/ T4/T5 clinical healing and no radiological signs of MRONJ. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Clinical and radiological diagnosis of MRONJ
- Patients with MRONJ non-eligibilible to the standard treatment (medical or surgical alone) for unstable systemic conditions or for unaccepted consent due.
Key exclusion criteria (2 listed)
- Head and neck radiotherapy
- Long term sistemic antimicrobial therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OZOPROMAF_SEQ1OZOPROMAF protocol consists of: local superficial anesthesia by EMLA® cream, intra-tissue injection of a 15 ml OxigenOzone (mixture by 26Gx 1⁄2 - 0.45x13mm needle into the mucosal margin surrounding the bone exposure or around the situs already evidenced by CT scan. It is applied on 7-15 days, depending on the patient compliance, until the formation of sequestrum and clinical healing (T1). Pain intensity is assessed by means of a questionnaire for pain and/or other symptoms evaluation before and after the protocol, based on numerical rating scale (NRS). After resolution (T1), follow-up visits are scheduled to confirm the healing of MRONJ at 1 (T2), 3, 6 (T3), 12 (T4), 18- 24 months (T5). Radiographic evaluations of bone healing are scheduled at T3 and T4. Positive outcomes for the OZOPROMAF protocol are evaluated at T1 as no clinical signs of acute phlogosis and no symptoms compatible with MRONJ; at T5 as clinical healing and no radiological signs of MRONJ. | Drug | OZOPROMAF_SEQ1 |
Primary outcome
MUCOSAL HEALING
Time frame: 3 months
no clinical signs and no symptoms compatible with MRONJ outcome measure: * formation of sequestrum by visualization of bone sequestrum * no infectius signs by visual inspection * no pain by NAS
MUCOSAL HEALING (1-T2)
Time frame: 3 months (T2)
no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection
MUCOSAL HEALING (2-T2)
Time frame: 3 months (T2)
no symptoms Outcome measure: pain evaluation by NAS
BONE HEALING (T2)
Time frame: 3 months (T2)
Outcome measure: no radiological signs compatible with MRONJ by OPT (orthopantomograph)
MUCOSAL HEALING (1-T3)
Time frame: 6 months (T3)
no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection
MUCOSAL HEALING (2-T3)
Time frame: 6 months (T3)
no symptoms Outcome measure:pain evaluation by NAS
BONE HEALING (T3)
Time frame: 6 months (T3)
Outcome measure: no radiological signs compatible with MRONJ by CT (computed tomography)
MUCOSAL HEALING (1-T4)
Time frame: 12 months (T4)
no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection
MUCOSAL HEALING (2-T4)
Time frame: 12 months (T4)
no symptoms Outcome measure:pain evaluation by NAS
BONE HEALING (T4)
Time frame: 12 months (T4)
Outcome measure: no radiological signs compatible with MRONJ by CT (computed tomography)
MUCOSAL HEALING (1-T5)
Time frame: 18-24 months (T5)
no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection
MUCOSAL HEALING (2-T5)
Time frame: 18-24 months (T5)
no symptoms Outcome measure: pain evaluation by NAS
BONE HEALING (T5)
Time frame: 18-24 months (T5)
Outcome measure: no radiological signs compatible with MRONJ by CT (computed tomography)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2021.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patients included in our study are selected due to their non-eligibility to the standard treatment (conservative/medical for long term or surgical alone) for unstable systemic conditions or unaccepted consent due to extensive proposed approach due to the advanced disease.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olga Di Fede, Professor principal investigator
University of Palermo - Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing OZOPROMAF_SEQ1 in people with MEDICATION RELATED OSTEONECROSIS OF THE JAW, run by University of Palermo 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 2 inclusion and 2 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: paused, as of the sponsor's last update on 8 Sep 2021. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
MUCOSAL HEALING (time frame: 3 months). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Sep 2021.