- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05664815
Human Amniotic Membrane (hAM) for Stage II Maxillomandibular Osteonecrosis Management (amniOST)
Benefit of Cryopreserved Human Amniotic Membrane (hAM) on Oral Mucosal Healing Among Patients With Stage II Maxillomandibular Osteonecrosis Induced by Antiresorptive and/or Anti-angiogenic Therapies: a Phase II Randomized Trial
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Florelle GINDRAUX, PhD
- Phone Number: 033381218998
- Email: fgindraux@chu-besancon.fr
Study Locations
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-
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Besançon, France, 25030
- Recruiting
- CHU de Besançon
-
Contact:
- astrid POZET
- Phone Number: +33381218988
- Email: apozet@chu-besancon.fr
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Principal Investigator:
- Aurélien LOUVRIER, MD-PhD
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Bordeaux, France
- Not yet recruiting
- CHU Bordeaux Pellegrin
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Contact:
- Mathilde FENELON, MD
- Email: mathilde.fenelon@chu-bordeaux.fr
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Dijon, France
- Not yet recruiting
- CHU de Dijon
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Contact:
- Narcisse ZWETYENGA, MD
- Email: narcisse.zwetyenga@chu-dijon.fr
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Metz, France
- Not yet recruiting
- CHR Metz Thionville
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Contact:
- Remi CURIEN, MD
- Email: r.curien@chr-metz-thionville.fr
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Reims, France
- Not yet recruiting
- CHU de Reims
-
Contact:
- Sébastien LAURENCE, MD
- Email: slaurence@chu-reims.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
INCLUSION CRITERIA
- Men and women over the age of 18
- Patient treated in the context of a tumor pathology during which he received treatment with bisphosphonates, Denosumab or anti-angiogenics, and/or, very often, switch of treatment or combination. Current treatment or mention of treatment in patient history
- MRONJ stage II certified clinically and radiologically. Also in the maxilla, stage II MRONJ without bucco-sinus communication after excision of the necrotic bone. Similarly, if a tooth with antral roots must be extracted and creates a bucco-sinus communication, if a MRONJ results, it will be stage II
- Patients with stage II MRONJ of childbearing age with current contraception or patients already postmenopausal
- Signature of the informed consent to participate indicating that the subject has understood the purpose and the procedures required by the study, that he agrees to participate in the study as well as to comply with the requirements and restrictions inherent in this study
- Affiliation to a French social security scheme or beneficiary of such a scheme
NON-INCLUSION CRITERIA
- Life expectancy of less than 6 months assessed by oncologists
- Existence of an evolving cervico-facial neoplasia or an evolving oral neoplastic process informed by oncologists
- History of oral and/or cervico-facial radiotherapy
- Allergy to one of these two antibiotics: amoxicillin-clavulanic acid or clindamycin-metronidazole combination
- Patient contraindicated for surgery due to his state of health, with general anesthesia or local anesthesia.
- MRONJ stage I and stage III
- Stage II MRONJ in patients with only osteoporosis
- Patients receiving treatments that may affect bone and/or mucous tissue as well as their metabolism: Patients on long-term corticosteroid therapy or immunosuppressants
- Patients with other diseases that may affect bone and/or mucous tissue as well as their metabolism: Bone diseases (such as brittle bone disease or Osteogenesis imperfecta, primary bone tumors in the maxilla or mandible (osteosarcoma, sarcoma, rhabdomyosarcoma ,…), any other malignant bone tumour; metabolic diseases with bone repercussions (Paget's disease, osteomalacia,…)
- Patients of childbearing age without contraception
- Legal incapacity or limited legal capacity
- Subject unlikely to cooperate in the study and/or low cooperation anticipated by the investigator
- Subject not affiliated to a social security scheme
- Patient under guardianship, curatorship or imprisonment
- Patient who notified his refusal to participate in the research
- Patient who participates in another clinical research
EXCLUSION CRITERIA
- During surgery: Discovery of an interrupting MRONJ with damage to the basilar edge (which corresponds to stage III).
- During surgery: Following a sequestrectomy discovery of spontaneous or ongoing healing.
- During the inclusion period: Patient to benefit from invasive "dental" surgeries directly related to bone exposure and in conjunction with taking risky molecules (factors favoring the occurrence of MRONJ): dental avulsions, curettage apical granulomas or cysts, endodontic treatments, or alveolar bone procedure (regularization of ridges).
- During the inclusion period: Patient with metastases all over the mandible.
- During the inclusion period: State of health of the patient which deteriorates due to his cancer during the inclusion period.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Application of human amniotic membrane (hAM)
After conventional/standard treatment, hAM will be applied in a single layer against the bone defect before closure.
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After conventional/standard treatment, hAM will be applied in a single layer against the bone defect with, if possible, a burial of a few millimeters under the mucous edges. With the idea of apprehending a possible dose effect, the hAM will be adapted to the size of the bone/mucous defect, mesenchymal side against the bone. For closure after hAM grafting : 2 options are possible: Edge-to-edge closure if sufficient mucosal laxity, Edge rapprochement by cross points. If necessary: possible incision of the periosteum to give laxity to the mucosa.
Other Names:
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Active Comparator: Conventional/standard treatment
Conventional/standard surgery.
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Surgical procedure: Endo-oral approach:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients with re-apparition of bone exposure
Time Frame: 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
|
Between Day 1 post-surgery and Month 3 post-surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patient with re-opening of the scar / reappearance of the bone exposure added visually during the control visit
Time Frame: Day 0 (the day of the surgery) or Day 1 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
|
Day 0 (the day of the surgery) or Day 1 post-surgery
|
Number of patient with re-opening of the scar / reappearance of the bone exposure added visually during the control visit
Time Frame: Visit 1 (7 to 10 days 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
|
Visit 1 (7 to 10 days post-surgery)
|
Number of patient with re-opening of the scar / reappearance of the bone exposure added visually during the control visit
Time Frame: Visit 2 (14 to 15 days 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
|
Visit 2 (14 to 15 days post-surgery)
|
Number of patient with re-opening of the scar / reappearance of the bone exposure added visually during the control visit
Time Frame: Visit 3 (One month 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
|
Visit 3 (One month post-surgery),
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Number of patient with re-opening of the scar / reappearance of the bone exposure added visually during the control visit
Time Frame: Visit 5 (6 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
|
Visit 5 (6 months post-surgery)
|
Number of patient with re-opening of the scar / reappearance of the bone exposure added visually during the control visit
Time Frame: 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
|
Visit 6 (12 months post-surgery)
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To assess pain with Visual Analogue Scale
Time Frame: Day 0 or Day 1 (if hospitalized patient)
|
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.
|
Day 0 or Day 1 (if hospitalized patient)
|
To assess pain with Visual Analogue Scale
Time Frame: Visit 1 (7 to 10 days 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.
|
Visit 1 (7 to 10 days post-surgery)
|
To assess pain with Visual Analogue Scale
Time Frame: Visit 2 (14 to 15 days 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.
|
Visit 2 (14 to 15 days post-surgery)
|
To assess pain with Visual Analogue Scale
Time Frame: Visit 3 ( 1 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.
|
Visit 3 ( 1 Month post-surgery)
|
To assess pain with Visual Analogue Scale
Time Frame: Visit 4 (3 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.
|
Visit 4 (3 Month post-surgery),
|
To assess pain with Visual Analogue Scale
Time Frame: Visit 5 (6 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.
|
Visit 5 (6 Month post-surgery)
|
To assess pain with Visual Analogue Scale
Time Frame: 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.
|
Visit 6 ( 12 Month post-surgery)
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Proportion of subjects with a complication at the site of mucosal healing
Time Frame: Day 0 or Day 1 post-surgery (if hospitalized patient)
|
On examination of the area of interest, during each visit, search for the presence of:
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Day 0 or Day 1 post-surgery (if hospitalized patient)
|
Proportion of subjects with a complication at the site of mucosal healing
Time Frame: visit 1 (7 to 10 days post-surgery)
|
On examination of the area of interest, during each visit, search for the presence of:
|
visit 1 (7 to 10 days post-surgery)
|
Proportion of subjects with a complication at the site of mucosal healing
Time Frame: Visit 2 (14 to 15 days post-surgery)
|
On examination of the area of interest, during each visit, search for the presence of:
|
Visit 2 (14 to 15 days post-surgery)
|
Proportion of subjects with a complication at the site of mucosal healing
Time Frame: Visit 3 (Month1 post-surgery)
|
On examination of the area of interest, during each visit, search for the presence of:
|
Visit 3 (Month1 post-surgery)
|
Proportion of subjects with a complication at the site of mucosal healing
Time Frame: Visit 4 ( 3 Month post-surgery)
|
On examination of the area of interest, during each visit, search for the presence of:
|
Visit 4 ( 3 Month post-surgery)
|
Proportion of subjects with a complication at the site of mucosal healing
Time Frame: Visit 5 (6 Month post-surgery)
|
On examination of the area of interest, during each visit, search for the presence of:
|
Visit 5 (6 Month post-surgery)
|
Proportion of subjects with a complication at the site of mucosal healing
Time Frame: Visit 6 (Month 12 post-surgery)
|
On examination of the area of interest, during each visit, search for the presence of:
|
Visit 6 (Month 12 post-surgery)
|
quality of life related to oral health
Time Frame: Day 0 or Day +1 post-surgery (if hospitalized patient)
|
Oral health impact profile OHIP 14 quality of life score
|
Day 0 or Day +1 post-surgery (if hospitalized patient)
|
quality of life related to oral health
Time Frame: Visit1 (7 to10 days post-surgery)
|
Oral health impact profile OHIP 14 quality of life score
|
Visit1 (7 to10 days post-surgery)
|
quality of life related to oral health
Time Frame: Visit 2 (14 to 15 days post-surgery)
|
Oral health impact profile OHIP 14 quality of life score
|
Visit 2 (14 to 15 days post-surgery)
|
quality of life related to oral health
Time Frame: V3 (Month 1 post-surgery),
|
Oral health impact profile OHIP 14 quality of life score
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V3 (Month 1 post-surgery),
|
quality of life related to oral health
Time Frame: Visit 4 ( Month 3 post-surgery)
|
Oral health impact profile OHIP 14 quality of life score
|
Visit 4 ( Month 3 post-surgery)
|
quality of life related to oral health
Time Frame: Visit 5 (Month 6 post-surgery)
|
Oral health impact profile OHIP 14 quality of life score
|
Visit 5 (Month 6 post-surgery)
|
quality of life related to oral health
Time Frame: Visit 6 (Month 12 post-surgery)
|
Oral health impact profile OHIP 14 quality of life score
|
Visit 6 (Month 12 post-surgery)
|
Proportion of subjects with new bone formation
Time Frame: Visit 4 (Month 3)
|
Presence of newly formed bone assessed by cone-beam imaging
|
Visit 4 (Month 3)
|
Proportion of subjects with new bone formation
Time Frame: Visit 5 (Month 6)
|
Presence of newly formed bone assessed by cone-beam imaging
|
Visit 5 (Month 6)
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Collaborators and Investigators
Investigators
- Principal Investigator: Aurélien LOUVRIER, MD, PhD, CHU de Besançon
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2021/584
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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