Human Amniotic Membrane (hAM) for Stage II Maxillomandibular Osteonecrosis Management

Phase 2

Recruiting

• Conditions: Osteonecrosis Due to Drugs, Jaw
• Interventions: Biological: Human Amniotic Membrane; Other: Conventional/Standard treatment

• Registration Number: NCT05664815
• Lead Sponsor: Centre Hospitalier Universitaire de Besancon

Brief Summary

This study aims to demonstrate, during the first standard surgical management of patients with stage II MRONJ, the effect of the implantation of a cryopreserved hAM on the maxillomandibular bone, on the healing of the oral mucosa.

Detailed Description

Medication-Related Osteonecrosis of the Jaw (MRONJ) is a complication of taking anti-tumor (anti-angiogenic) and bone anti-resorptive treatments (biphosphonates, Denosumab) which impact bone healing and renewal capacities, which can lead to bone necrosis. It affects 1 to 10% of patients and is classified into 4 stages.

There is no reference document for their management, which requires antibiotics, local antiseptics and tissue debridement sometimes associated with sequestrectomy. The objective of treatment is very often to obtain healing of the oral mucosa to cover the exposed bone. Without treatment, stage II MRONJ can progress to stage III, with orostoma, pathological fractures and extra-fistula.

The human amniotic membrane (hAM) has poor (even no) immunogenicity and exerts an anti-inflammatory, anti-fibrotic, antimicrobial, antiviral and analgesic effect. It is a source of multipotent stem cells and growth factors that promote tissue regeneration.

A pioneering, non-comparative study reports the use of hAM in MRONJ with very encouraging results in terms of re-epithelialization, absence of pain and infection (Ragazzo 2018). Recently, the same team published a retrospective study where 49 patients (stage 1 to 3) were included, including 27 treated with hAM (Ragazzo 2021). They report a significant improvement in quality of life and pain in the treated group.

hAM would provide a new approach in the treatment of stage II MRONJ by acting on: the quality and speed of mucosal healing, pain, even infection and regeneration of the underlying bone.

This study aims to demonstrate, during the first standard surgical management of patients with stage II MRONJ, the effect of the implantation of a cryopreserved hAM on the maxillomandibular bone, on the healing of the oral mucosa three months after the operation.

In second objectives will be evaluated: pain, complications at the site of healing of the mucosa (erythema, abscess, purulent discharge, diffuse infection of soft tissues (cellulitis), orostoma, suborbital abscess, mandibular fracture), oral health -dental/quality of life and new bone formation at subsequent visits.

Study Timeline

• Study First Submitted: 2022-10-24
• Study First Submitted QC: 2022-12-21
• Study First Posted: 2022-12-27
• Study Start: 2023-09-22
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-11
• Last Update Posted: 2023-10-12
• Primary Completion: 2025-09
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Application of human amniotic membrane (hAM)	Human Amniotic Membrane	After conventional/standard treatment, hAM will be applied in a single layer against the bone defect before closure.
Conventional/standard treatment	Conventional/Standard treatment	Conventional/standard surgery.

Primary Outcome Measures

Name	Time	Method
Number of patients with re-apparition of bone exposure	Between Day 1 post-surgery and Month 3 post-surgery	Number of patients with re-apparition of bone exposure visually observed by the surgeon. Clinical examination: reopening of the scar / reappearance of exposed bone / taking a photograph of the treated area

Secondary Outcome Measures

Name	Time	Method
To assess pain with Visual Analogue Scale	Visit 6 ( 12 Month post-surgery)	Pain assessed by a Visual Analogue Scale (VAS). This EVA scale will be supplemented by a collection of information on the use of analgesics if necessary. Also patients who would have to take analgesics will fill out a "logbook" which will specify the class of the drug and the dosage.
Number of patient with re-opening of the scar / reappearance of the bone exposure added visually during the control visit	Visit 6 (12 months post-surgery)	Re-apparition of bone exposure visually observed by the surgeon. Clinical examination: reopening of the scar / reappearance of exposed bone / taking a photograph of the treated area
quality of life related to oral health	Visit 6 (Month 12 post-surgery)	Oral health impact profile OHIP 14 quality of life score
Proportion of subjects with a complication at the site of mucosal healing	Visit 6 (Month 12 post-surgery)	On examination of the area of interest, during each visit, search for the presence of: * Minor complications: pain and/or erythema and/or abscess and/or purulent discharge,; * Major complications: diffuse soft tissue infection (cellulitis), orostoma, suborbital abscess, mandibular fracture.
Proportion of subjects with new bone formation	Visit 5 (Month 6)	Presence of newly formed bone assessed by cone-beam imaging

Trial Locations

Locations (5)

CHU de Dijon; 🇫🇷 Dijon, France

CHU de Besancon; 🇫🇷 Besançon, France

CHU Bordeaux Pellegrin; 🇫🇷 Bordeaux, France

CHR Metz Thionville; 🇫🇷 Metz, France

CHU de Reims; 🇫🇷 Reims, France