E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients in need of dental implant(s) in the upper and lower jaws with presence of bone defects with loss in vertical height and < than 4 mm in lateral width
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E.1.1.1 | Medical condition in easily understood language |
Lack of bone width (and sometimes hight), so that it is not possible to place dental implants. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Mouth and tooth diseases [C07] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Principal objective: To compare linear changes in bone width between the tested interventions aimed for vertical and lateral bone augmentation; test (combination of autologous culture expanded mesenchymal stem cells and biomaterials) and control groups (autologous bone block graft from ramus fixed with osteosynthesis screws) |
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E.2.2 | Secondary objectives of the trial |
(1) To evaluate efficacy of treatment and formation of new bone by: assessing the possibility to insert an implant 5 months after the grafting procedure (3D CBCT) Measuring clinical changes in alveolar bone width. evaluating the collected core biopsies using μCT, SRμCT and histology. evaluting outcomes after implant placement (2) To evaluate the safety of the interventions by: assessing adverse effects (AEs) and soft tissue healing at 2 and 4 weeks and 5 months assessing the morbidity associated with both procedures by measuring the usage of postoperative anti-inflammatory medication and degree of reported pain using a VAS scale assessing fate of the transplanted MSCs by liquid biopsy (blood samples and plasma/sera at screening and 2 weeks after bone augmentation surgery) (3) To assess patient’s satisfaction with surgical intervention and prosthetic outcome by patient reported outcomes (PROMs). Impact of treatment on the patient’s overall quality of life (QoL) will be assessed |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Written informed consent Patient should be able to understand and complete the informed consent Age 18 years or older Insufficient bone ridge width (≤ than 4 mm) and or height at the recipient site for titanium dental implant placement Patient should be eligible for bone marrow harvest and bone transplant Healthy oral mucosa, at least 2 mm keratinized mucosa Female candidates of child bearing potential (WOCBP) -as defined by CTFG 2- must be referred to their physician for a pregnancy test 1,2 before inclusion in the study. In case of a negative preganancy test their physician will be asked to prescribe one of the highly effective birth control methods recommended by CTFG 2 which includes: 1. Combined estrogen and progestogen containing contraceptives that are associated with inhibition of ovulation (oral, intravaginal or transdermal). 2. Progestogen-only hormonal contraceptives associated with inhibition of ovulation (oral, injectable or implantable). 3. Intrauterine devices. 4. Intrauterine hormone-releasing system. 5. Bilateral tubal occlusion. 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 (5 months after bone augmentation procedure considering that pregnancy is not considered as a contraindication for normal dental implant). 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). |
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E.4 | Principal exclusion criteria |
General contraindications for dental and/or surgical treatments · Contraindications for both bone marrow harvesting and bone grafts: o General: § Patients with severe bone marrow diseases such as leukemias, lymphomas, and myelodysplastic syndromes. § Patients with severe respiratory disease, chronic respiratory failure, medical history of generalized allergic manifestation. § Patients with a history of severe osteoporosis. § Patients suffering from any serious coagulation disorders that could require substitution therapy. § Patients receiving anticouagulant treatment should be adjusted in collaboration with the treating physician. § Patients with total hip prothesis o Local: § Patients with active infection at the harvest site § Patients with previous pathology or trauma at the harvest site · History of any malignant diseases · Concurrent or previous radiotherapy of head and neck region · History of contagious diseases (HIV, HTLV and/or syphilis seropositivity, hepatitis B or C infection) · 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). · Inflammatory and autoimmune disease of the oral cavity. · Concurrent or previous immunosuppressant, bisphosphonate or high dose corticosteroid therapy. · Patients with a history of drug addiction. · Patients with known hypersensitivity against paracetamol, codein or xylocaine. · Thin keratinized mucosa (< 1mm) · 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). · Pregnant or lactating women. · Participation in an investigational device, drug or biologics study within the last 24 weeks prior to the study start |
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E.5 End points |
E.5.1 | Primary end point(s) |
Principal assessment is linear change in bone width 2 mm below alveolar crest measured by means of CBCT images from baseline to 5 months after the regenerative surgery, immediately prior to implant placement.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
PROMS, implant stability, QoL, AE assessment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |