The First/Second Stage of Open Clinical Examination: Application of Novel Bone Substitute (ALBO-OS) in Patients With Periodontal Disease or Have a Need for Alveolar Preservation
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Healing of periodontal pockets or alveolar sockets without any known adverse events
研究概览
简要总结
The recent Global Burden of Disease Study indicates that severe periodontitis is the 6th most prevalent disease worldwide, with an overall prevalence of 11.2% and around 743 million people affected, and the global burden of periodontal disease increased by 57.3% from 1990 to 2010. As periodontitis is the major cause of tooth loss in the adult population worldwide, these individuals are at risk of multiple tooth loss, edentulism, and masticatory dysfunction, thereby affecting their nutrition, quality of life, and self-esteem, as well as imposing huge socioeconomic impacts and healthcare costs. The global burden of periodontal diseases remains high, and trends in risk factors, improved tooth retention, and an aging population are likely to bear further increases. Associated morbidity, costs, and socio-economic impact will continue to rise.
In addition to the need to treat more severe forms of periodontitis by implanting bone substitutes inside periodontal pockets, there are extremely frequent requests to preserve the alveolus after tooth extraction.
Alveolar ridge preservation is a popular technique, currently accounting for about 29% of all procedures involving bone substitutes. Application of this technique is necessary if the subsequent installation of dental implants based on titanium alloys is planned. The prevalence of this technique in dental medicine is also indicated by the fact that the global cost of bone replacement materials for the preservation of the alveolar ridge is estimated at 190 million dollars per year, with an expected annual growth of approximately 11.4%.
The implantation of the ALBO-OS for the treatment of periodontal pockets with probing depth more than 5mm and alveolar ridge augmentation is considered an essential method for significant improvement of oral health for patients with advanced periodontitis. Following the main requirements for an ideal bone substitute for filling the periodontal pockets and alveolar sockets, such as its high porosity, satisfactory chemistry and surface topography characteristics, as well as desirable microstructure and mechanical properties, ALBO-OS shows numerous advantages compared with recently developed used bone grafts, particularly expressed in their excellent osteoconductive and osteoinductive properties, have been approved on a wide scale of animal assays.
Therefore, it will be applied in clinical trials for the healing of severe periodontitis disease when implantation of the bone substitute is required. Financial support of the study is provided by the sponsor's consortium, with ALBOS Ltd as the main sponsor. The recruitment site is the Home Health, Foča, Republic of Srpska, Bosnia and Herzegovina.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •in case of regenerative periodontal treatment:
- •Informed consent has been signed
- •Age 18 years and above
- •Stable dose of current regular medication (specify type if needed) for at least 4 weeks before trial entry
- •Acceptable laboratory analysis
- •No systemic diseases which could influence the outcome of the therapy, or interfere in any way with treatment outcomes, such as they are: an acute or chronic infection (e.g., osteomyelitis) at the site of implantation, uncontrolled metabolic diseases such as diabetes, osteomalacia, disorders of the thyroid gland, or heavy disturbances in the liver or kidney
- •Good compliance with individual plaque control following initial periodontal therapy
- •Teeth to be involved should be vital (intact or with fillings but without the presence of caries lesion) with score 0 mobility
- •The selected 2- or 3-wall intrabony defect depth, which ranges from 3-5 mm, as detected in diagnostic Panoramic Radiograph and clinical examination
- •Selected pocket depth (PD) ≥ 5 mm and clinical attachment level (CAL) ≥ 3 mm at the site of the endosseous defect
- •Angle radiographic bone defect ≤55 and ≥15
- •The availability of program monitoring and maintenance of oral hygiene
- •No history of periodontal therapy in the previous 6 months
- •No history of antibiotics' intake or other medications affecting the periodontium in the previous 3 months
- •Minimum number of teeth is 16 (50% of all teeth/mouth) to achieve a desirable treatment effect
- •To preserve the dimensions of the bone of the alveolar ridge, in the indication of alveolus preservation, immediately after previous tooth extraction, in the case of planned installation of implants based on titanium alloys, it is necessary to preserve the alveolus for at least two months before implant installation
排除标准
- •in case of regenerative periodontal treatment:
- •Pregnancy and lactation 6 months before the study and during the study
- •Significant renal or hepatic impairment
- •Scheduled elective surgery or other procedures requiring general anesthesia or local (oral) surgery during the trial
- •Subject with a life expectancy of less than 6 months
- •Periodontal treatment for the previous year
- •Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
- •Participation in another research trial involving an investigational product of a similar type in the past 12 weeks
- •Eligibility criteria if ARP was indicated:
- •Inclusion criteria: age ≥18 years; good general health; non-smokers or light smokers (up to 10 cigarettes per day); no active periodontal disease; presence of single or multiple hopeless teeth; tooth/teeth to be extracted having at least one neighboring tooth and at least two socket walls with 3 mm of alveolar bone height; more than two residual teeth after extraction to be used as references during image superimposition.
- •Exclusion criteria: pregnancy or lactation; presence of systemic conditions and medications that alter bone metabolism (i.e. uncontrolled diabetes mellitus, renal or hepatic impairment, immunodeficiency, severe autoimmune diseases, malignancy, radiotherapy or chemotherapy in the past 5 years, intake of corticosteroids, bisphosphonates or other anti-resorptive drugs); active periodontal disease; heavy smoking (more than 10 cigarettes per day).
结局指标
主要结局
Healing of periodontal pockets or alveolar sockets without any known adverse events
时间窗: up to 12 months
* vital signs, and laboratory tests were monitored * in case of an adverse event occurrence, the symptoms, onset date, resolution date, and the degree of severity will be recorded. The three levels of adverse events intensity are defined: mild, moderate, and severe.
Formation and osseointegration of the new bone tissue inside periodontal pockets with an initial periodontal probing depth of more than 5 mm, caused by the implantation of the new bone substitute, explained by PPD
时间窗: 6 months
Changes of the depth of periodontal pockets: Changes of the initial periodontal probing depth (PPD) ≥ 5 mm, caused by formation of the new bone tissue inside periodontal pockets, determined by CBCT, comparing their dimensions before implantation and 6 months after implantation of bone substitute, in mm.
Formation and osseointegration of the new bone tissue inside periodontal pockets with initial periodontal probing depth more than 5 mm, caused by the implantation of the new bone substitute, explained by CAL
时间窗: 6 months
Changes of the depth of periodontal pockets: Changes from baseline clinical attachment level (CAL) measured by CBCT as a distance from the cementoenamel junction (CEJ) to the bottom of the periodontal pocket (PD) before implantation and 6 months after implantation of bone substitute, in mm.
Healing bone tissue inside periodontal pockets with an initial periodontal probing depth of more than 5 mm (or alveolar socket following alveolar ridge preservation), caused by the implantation of the new bone substitute, explained by GI
时间窗: baseline, 4 and 6 months after the surgical procedure
Gingival index (GI) is a numerical index for determining the level of gingival inflammation. LoeSilness was used as a numerical index to determine the level of gingival inflammation following the Gingival Index criteria: 0: Normal gingiva 1. Mild inflammation (slight color change and edema, but no bleeding on probing) 2. Moderate inflammation (redness, edema, glazing, and bleeding on probing) 3. Severe inflammation (marked redness and edema, ulceration, and tendency to spontaneous bleeding.
Healing bone tissue inside periodontal pockets with an initial probing depth of more than 5 mm (or alveolar socket following alveolar ridge preservation), caused by the implantation of the new bone substitute, explained by PI
时间窗: baseline, 4 and 6 months after the surgical procedure
Plaque index (PI) is a numerical index for determining the level of oral hygiene. SilnessLoe prices are given as follows: 0 - No plaque 1. \- Plaque adhering to the gingival margin and adjacent area of the tooth. The plaque can be seen in situ only after application of a disclosing solution or by using the probe on the tooth surface. 2. \- Moderate accumulation of soft deposit within the gingival pockets, or the tooth and the gingival margin, which can be seen with the naked eye. 3. \- Abundance of soft matter within the gingival pockets (PI index was calculated by using formula: PI=Ʃ Scores for plaque/4 surfaces x number of teeth).
Healing bone tissue inside periodontal pockets with an initial probing depth of more than 5 mm, explained by MMI
时间窗: 6 months
The Miller mobility index (MMI) is a numerical index for determining the mobility of the tooth. It assesses the horizontal and vertical movement of a tooth within its socket to determine periodontal health. Grade 0: Physiological mobility, undetectable/normal (up to 0.2) Grade 1: Slight mobility (horizontal movement between (0.2-1mm) Grade 2: Moderate mobility (horizontal movement \> 1mm) Grade 3: Severe mobility (horizontal movement \>1 mm and vertical displacement (depressible)).
Alveolar ridge height in mm (by means of CBCT)
时间窗: baseline and 4 months following surgical procedure
A horizontal reference line is defined tangential to the most apical point of the extraction socket, whereas a vertical reference line was marked perpendicular to it, passing through the central axis of the socket, respectively. Regarding alveolar ridge height two vertical dimensions will be evaluated along the vertical reference line. The vestibular (VH) and oral (OH) heights of alveolar ridge (in mm) are defined as the distances from the horizontal reference line to the most coronal points of the buccal and oral aspects of the bone cortical level (BCL), respectively.
Alveolar ridge width in mm (by means of CBCT)
时间窗: Baseline and 4 months following surgical procedure
For measurements of alveolar ridge width (in mm) three horizontal parameters are positioned perpendicular to the vertical reference line at three standardized levels apical to the crestal bone level: HW-1: 1 mm apical to the crest; HW-3: 3 mm apical to the crest; HW-5: 5 mm apical to the crest
Histological analysis
时间窗: 4 months following ARP
Bone samples harvested at the time of implant placement following alveolar ridge preservation will be evaluated and histologically described in detail. The hard tissue specimens will fixed in 4% buffered buffered formaldehyde, following by decalcification in formic acid idehydration with increasing concentrations of ethanol. The next step will be embedding the tissue in a supportive medium-paraffin wax. Serial longitudinal sections measuring 0.004 mm in thickness will be prepared by means of microtome. Finally, the sections will be stained in Hematoxylin and Eosin to make cell components visible and mounted for microscopic examination. The histological examination will be carried out using light microscopy (Leitz Labor Lux S fluorescent microscope, Ernst Leitz Wetzlar GMBH, Wetzlar, Germany). The morphometric evaluation was performed at 400× magnification using a digital camera system (Leica DFC295, Wetzlar, Germany).
次要结局
- Buccal bone plate thickness (in mm), by means of CBCT(baseline and 4 months following surgical procedure)
- The percentage of radiographic linear socket fill (%), by means of CBCT(4 months following ARP)
- Bleeding on probing (by means of periodontal probe)(baseline and 4 months following surgical procedure)