A multicentre clinical trial: Alveolar bone augmentation using MSCs and biphasic calcium phosphate granules prior to dental implants (Behandling Maxillofacial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University of Bergen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

1 Jul 2018 → 6 Mar 2025

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517976-39-00

EudraCT number

2018-004046-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To assess the safety and efficacy of using autologous mesenchymal stem cells and biomaterials to regenerate bone in order to enable adequate implant placement.

Secondary objectives 3

1. To evaluate efficacy of treatment and formation of new bone
2. To evaluate the safety of the interventions
3. To assess patient’s satisfaction with surgical intervention and prosthetic outcome

Conditions and MedDRA coding

Alveolar bone augmentation in patient with bone defects in jaw with < than 4 mm in lateral width

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent.
2. Patient should be able to understand and complete the informed consent.
3. Age 18 years or older.
4. Insufficient bone ridge width (≤ than 4 mm) and or height at the recipient site for implant placement.
5. Healthy oral mucosa, at least 2 mm keratinized mucosa.
6. Female candidates of child bearing potential (WOCBP) -as defined by CTFG 2 (a woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile due surgery)- must be referred to their physician for a pregnancy test 1,2 before inclusion in the study. (See the study protocol for full list of acceptable contraceptives and requirements for pregnancy testing during the study)
7. The WOCBP candidates will only be included in the study if the pregnency tests are negative. These patients must continue using the contraceptives until the placement of dental implants (6 months after bone augmentation procedure considering that pregnancy is not considered as a contraindication for normal dental implant).
8. Female candidates that have entered menopause for less than 12 months must also be referred to confirm post-menopausal state by testing the level of follicle stimulating hormone (FSH).

Exclusion criteria 14

1. General contraindications for dental and/or surgical treatments
2. Patients with a history of drug addiction.
3. Patients with known hypersensitivity against antibiotics (both Amoxicillin and Clindamycin), all painkillers (paracetamol, ibuprofen and level II painkillers) or xylocaine. Mouthwashes as chlorhexidine and anti-inflamatory agents will be used carefully considering possible allergies and contraindications for using these products.
4. Thin keratinized mucosa (< 1mm)
5. Current smokers and those who have quitted smoking in the last 4 weeks (there is evidence that nicotine and cotinine levels disappear after 4 weeks of non-smoking).
6. Pregnant or lactating women.
7. Participation in an investigational device, drug or biologics study within the last 24 weeks prior to the study start
8. Contraindications for bone marrow harvesting (general):1) Patients with severe bone marrow diseases such as leukemias, lymphomas, and myelodysplastic syndromes. 2) Patients with severe respiratory disease, chronic respiratory failure, medical history of generalized allergic manifestation. 3) Patients with a history of severe osteoporosis. 4) Patients suffering from any serious coagulation disorders that could require substitution therapy. 5) Patients receiving anticouagulant treatment should be adjusted in collaboration with the treating physician.
9. History of any malignant diseases
10. Concurrent or previous radiotherapy of head and neck region
11. History of contagious diseases (HIV, HTLV and/or syphilis seropositivity, hepatitis B or C infection)
12. Uncontrolled diabetes mellitis, e.g. patients with diabetes not regulated with medications or diet. This will be verified based on patient`s history and concurrent HbA1c levels (HbA1c > 53 mmol/mol).
13. Inflammatory and autoimmune disease of the oral cavity.
14. Concurrent or previous immunosuppressant, bisphosphonate or high dose corticosteroid therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Principal assessment is linear change in bone width 2 mm below alveolar crest measured by means of CBCT images from baseline to 6 months after the regenerative surgery, immediately prior to implant placement.

Secondary endpoints 10

1. Ability to place implants in the reconstructed area 6 months after the grafting procedure
2. Linear changes in mm measured with a gauge 2 mm below the alveolar crest, between the first surgery before applying the regenerative intervention and 6 months later at the second surgery, immediately before placing the implants
3. Adverse effects (AEs) and soft tissue healing (uneventful healing, wound dehiscence, membrane, exposure, redness, signs of infection, swelling) at 2 and 4 weeks and 6 months.
4. Morbidity associated with procedures: o Number and type of postoperative anti-inflammatory medication o The degree of reported pain using a VAS scale.
5. Patient’s satisfaction: - Patient reported outcomes (PROMs) using a structured questionnaire with Likert scales. - Patient’s overall quality of life (QoL) will be assessed with the use of validated tools: Health-related Quality of Life (HRQoL) and Oral Health-Related Quality of Life (OHRQoL).
6. Fate of the transplanted MSCs by liquid biopsy technology (screening, and 2 weeks after the bone augmentation) surgery by collecting peripheral blood samples and plasma/sera)
7. Bone promoting activity of the intervention by evaluating the core biopsies harvested during re-entry procedure at the sites receiving dental implant by micro-computed tomography (μCT) and histology
8. The need of secondary bone augmentation around the dental implants placed in correct prosthetic driven position
9. Implant stability at time of implant installation, at abutment surgery, at loading, and 12 months after loading (using Osstell® radiofrequency implant stability quotients).
10. Evaluate local conditions, hygiene and absence of inflammation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University of Bergen

Sponsor organisation

University of Bergen

Address

Aarstadveien 19

City

Bergen

Postcode

5009

Country

Norway

Scientific contact point

Organisation

University of Bergen

Contact name

Kamal Mustafa

Public contact point

Organisation

University of Bergen

Contact name

Kamal Mustafa

Third parties 1

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications