Infiltration of Medical Ozone for the Treatment of Medication-Related Osteonecrosis of the Jaws (MRONJ)

NCT05036837 | Suspended Phase 1 FDA Drug

• 1 other identifier: OZOPROMAF_SEQ1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

MEDICATION RELATED OSTEONECROSIS OF THE JAW

Keywords

MRONJ; Osteonecrosis; Jaw; Antiresorptive; Antiangiogenic drugs; Adverse event

Outcome Measures

Primary Outcomes (13)

• 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

  3 months

• MUCOSAL HEALING (1-T2)

  no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection

  3 months (T2)

• MUCOSAL HEALING (2-T2)

  no symptoms Outcome measure: pain evaluation by NAS

  3 months (T2)

• BONE HEALING (T2)

  Outcome measure: no radiological signs compatible with MRONJ by OPT (orthopantomograph)

  3 months (T2)

• MUCOSAL HEALING (1-T3)

  no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection

  6 months (T3)

• MUCOSAL HEALING (2-T3)

  no symptoms Outcome measure:pain evaluation by NAS

  6 months (T3)

• BONE HEALING (T3)

  Outcome measure: no radiological signs compatible with MRONJ by CT (computed tomography)

  6 months (T3)

• MUCOSAL HEALING (1-T4)

  no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection

  12 months (T4)

• MUCOSAL HEALING (2-T4)

  no symptoms Outcome measure:pain evaluation by NAS

  12 months (T4)

• BONE HEALING (T4)

  Outcome measure: no radiological signs compatible with MRONJ by CT (computed tomography)

  12 months (T4)

• MUCOSAL HEALING (1-T5)

  no clinical signs Outcome measure: no clinical signs compatible with MRONJ by visual inspection

  18-24 months (T5)

• MUCOSAL HEALING (2-T5)

  no symptoms Outcome measure: pain evaluation by NAS

  18-24 months (T5)

• BONE HEALING (T5)

  Outcome measure: no radiological signs compatible with MRONJ by CT (computed tomography)

  18-24 months (T5)

Study Arms (1)

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.

Drug: OZOPROMAF_SEQ1

Interventions

OZOPROMAF_SEQ1 DRUG

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.

OZOPROMAF_SEQ1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Head and neck radiotherapy
• Long term sistemic antimicrobial therapy

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (1)

Azienda Ospedaliera Universitaria Policlinico "P. Giaccone" Palermo - University of Palermo

Palermo, Italy - Sicily, 90127, Italy

Location

Related Links

• Related Info

MeSH Terms

Conditions

Osteonecrosis

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Olga Di Fede, Professor

  University of Palermo - Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: September 8, 2021
• Study Start: February 1, 2018
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2022
• Last Updated: September 8, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

IT (1)