Periodontal Bone LossEarly Phase 1NCT05360511
Erythropoietin Gel as an Adjunct to Xenograft in the Surgical Management of Intrabony Periodontal Defects
A Early Phase 1 study testing particulate xenograft + erythropoietin gel. and particulate xenograft in people with Periodontal Bone Loss, run by Ain Shams University at 1 site in Egypt.
Trial summary
The aim of the study is to evaluate the use of erythropoietin gel as an adjunct to xenograft in the surgical management of intrabony periodontal defects. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Periodontal Bone Loss
- What is being tested?
- particulate xenograft + erythropoietin gel. and particulate xenograft
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jul 2022to 1 Oct 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Both genders within age range of 20-50 years.
- Patients diagnosed with periodontitis (Stage III).
- Test site criteria: probing pocket depth ≥6mm and CAL ≥3mm. All these criteria will be determined after phase I conventional periodontal therapy.
- Patients with three-wall intrabony defect.
- Systemically free patients as evidenced by Burket's oral health history questionnaire .
- Ability to attend the treatment sessions and comply with its procedures, the recall visits and oral hygiene protocol.
Who cannot join
- Smokers.
- Pregnant or lactating females.
- Patients under any medication that affect periodontal healing.
- Vulnerable individuals
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Erythropoietin Gel as an Adjunct to Xenograft in the Surgical Management of Intrabony Periodontal Defects. A Randomized Controlled Clinical Study
The aim of the study is to evaluate the use of erythropoietin gel as an adjunct to xenograft in the surgical management of intrabony periodontal defects.
Read the detailed description
In the periodontal disease there is an interaction of the biofilm with the immune response of the host which results in an imbalance between bacterial virulence and the host defense causing changes in bone and connective tissue homeostasis .
Armitage's 1999 classified periodontitis to either chronic or aggressive . In 2017, the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) classified the periodontal disease using a new staging and grading system. Staging is determining the severity of the disease and the complexity of treatment of the disease, while grading gives additional data about the biological consideration of the disease, such as analyzing the history for the rate of progression and predicting the risk for further progression.
Periodontitis is classified to four stages ranging from Stage I: Initial periodontitis the clinical attachment level (CAL=1-2mm), Stage II: Moderate periodontitis (CAL= 3-4 mm), Stage III: Severe periodontitis and increased potential for tooth loss (<4), and (CAL ≥5mm), Stage IV: Severe periodontitis with increased risk for tooth loss (≥5) and (CAL≥5mm). Grading is determined by the risk factors like smoking, diabetes, and outcomes of scaling and root debridement. Grade A: Low rate of progression (no CAL loss over 5 years), Grade B: Moderate rate of progression (CAL loss<2mm over 5years), and Grade C: High rate of progression (CAL loss ≥2 mm over 5 years) .
The periodontal tissue break down happens because of both the direct effect of the microbial invasion and the indirect effect of the host immune response, this happens when the bacterial invasion results in bacterial products that cross the junctional epithelium which stimulates the host immune response resulting in tissue breakdown .
Pattern of bone destruction in periodontitis can be horizontal or vertical .Horizontal bone loss appears as an even bone destruction leading to a uniform decrease in the bone height in relation to the teeth. Vertical bone loss results in formation of a triangular area of missing bone, known as triangulation. Vertical bone loss could result in angular defects and intrabony pocket formation which become very challenging in treatment.
Treatment of periodontitis is targeting mainly the reduction of bacteria present in the subgingival biofilm. The non-surgical periodontal therapy is done by supragingival scaling and subgingival debridement of the roots using hand or power-driven scalers to eliminate all the deposits such as calculus, plaque and endotoxins
Mechanical instrumentation alone has some limitations especially in areas with deep pocket, areas with bony defects and also ineffective against some bacteria, such as Aggregatibacter actinomycetemcomitans(AA) .Therefore the use of chemotherapeutic agents as adjuncts to mechanical periodontal therapy has been strongly recommended .
Systemic and local antimicrobials are used as adjuncts to the non-surgical periodontal therapy, especially in patients with deep periodontal pockets and aggressive or refractory periodontitis .Also chemotherapeutic agents that target the host immune response result in better clinical effect when used as an adjunct to mechanical periodontal therapy .
According to the recent guidelines of the European Federation of Periodontology (EFP) when the pocket depth is 6mm or more after the non-surgical periodontal therapy with or without adjunctive chemotherapeutic agent, access flap surgery is recommended. Also they recommended treating the residual pockets associated with intrabony defect by periodontal regenerative surgery .
There is a positive correlation between the number of walls present and CAL gain, three-walled intrabony defects have 269% higher chance of >3mm CAL gain in comparison to one-walled defects .
Siciliano et al stated that there is a reduced CAL gain in the non-contained defects .
Different treatment approaches are used for periodontal regeneration such as barrier membranes, autografts, allografts, xenografts, biological agents (i.e. enamel matrix derivatives (EMD)), and growth factors .
The recent guidelines of the (EFP) recommended treatment of intrabony defects by periodontal regenerative surgery .
However, there is limited potential of bone grafts to enhance periodontal regeneration and basically they should be used to ensure space provision since the success of the periodontal regeneration surgery is limited by the available space under the mucoperiosteal flap .
In addition, there are some drawbacks with the use of membrane such as membrane exposure, wound infection and bacterial colonization. So, various biomaterials are tested to be used in combination with bone grafts .
Erythropoietin (EPO) is a hematopoietic hormone and has multiple biological effects. In 2014, Hamed et al showed the role of EPO in epithelial regeneration, healing process and its anti-inflammatory properties. In addition, it was concluded that the topical application of the EPO is a very safe route of administration with no systemic side effects. Also Wang et al in 2017 stated that the EPO upregulated the osteogenesis of the human periodontal mesenchymal stem cells by stimulating the expression of osteogenic genes
According to Zheng et al in 2019 the expression of Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and Osterix (which are transcription proteins that are responsible for osteoblastic differentiation) was verified in the periodontal ligament stem cells treated with EPO which confirms the relationship between EPO and osteogenic differentiation of periodontal ligament stem cells .
In a recent study by Aslroosta et al in 2021, he proved that the local delivery of EPO gel in non-surgical periodontal therapy can improve clinical inflammation and enhance the CAL gain .However, no clinical trials have been conducted to study the effect of EPO gel in the intrabony defects. Therefore the present study will be carried out to evaluate the clinical effect of using the EPO gel as an adjunct to xenograft in the surgical management of intrabony periodontal defects.
- Conditions
- Periodontal Bone Loss
- Being tested
- particulate xenograft + erythropoietin gel., particulate xenograft
- Medical subject headings
- Alveolar Bone Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
particulate xenograft + erythropoietin gel.Drug
Also called The mix of xenograft and EPO gel
- Surgical sites will be anaesthetized using local anaesthesia.
- Intrasulcular incision will be done in the periodontal pocket as close as possible to the tooth surface with the deepest point being the alveolar crest.
- The incisions will be extended to the mesial papilla of the tooth before the defect and the distal papilla of the tooth after the defect.
- Both buccal and lingual/palatal mucoperiosteal flaps will be raised using blunt dissection.
- Mechanical debridement of the infected tissue from the intrabony defect and root debridement will be done using Gracey curettes.
- In Group A (test group):
Particulate xenograft will be mixed with EPO gel and applied to fill the whole defect.
particulate xenograftCombination product
Also called The xenograft alone
- All surgeries will be performed by the same operator as follows:
- Surgical sites will be anaesthetized using local anaesthesia.
- Intrasulcular incision will be done in the periodontal pocket as close as possible to the tooth surface with the deepest point being the alveolar crest.
- The incisions will be extended to the mesial papilla of the tooth before the defect and the distal papilla of the tooth after the defect.
- Both buccal and lingual/palatal mucoperiosteal flaps will be raised using blunt dissection.
- Mechanical debridement of the infected tissue from the intrabony defect and root debridement will be done using Gracey curettes.
- In Group B (control group):
Particulate xenograft will be applied to fill the whole defect.
| Study group | Role | What they receive |
|---|---|---|
| Group A (Test group) | Experimental | Group A (Test group): Twelve patients will be subjected to open flap debridement and application of particulate xenograft + erythropoietin gel. Receives: Drug: particulate xenograft + erythropoietin gel. |
| Group B (Control group) | Active comparator | Group B (Control group): Twelve patients will be subjected to open flap debridement and application of particulate xenograft. Receives: Combination Product: particulate xenograft |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of Plaque index (PI):
it will be described by a number on a scale from 0 to 5 as follows: 0 = No plaque.1 = Separate flecks of plaque present at the cervical margin.2 = A thin, continuous band of plaque.3 = A band of plaque wider than 1 mm.4 = Plaque affecting at least 1/3, but not 2/3 of the side of the crown.5 = Plaque affecting 2/3 or more of the side of the crown.
Measured: at baseline (before the surgery by one week)
Evaluation of Plaque index (PI):
it will be described by a number on a scale from 0 to 5 as follows: 0 = No plaque.1 = Separate flecks of plaque present at the cervical margin.2 = A thin, continuous band of plaque.3 = A band of plaque wider than 1 mm.4 = Plaque affecting at least 1/3, but not 2/3 of the side of the crown.5 = Plaque affecting 2/3 or more of the side of the crown.
Measured: 6 months after the surgery.
Evaluation of the Sulcus bleeding index (SBI):
it will be described by a number on a scale from 0 to 5 as follows: 0: No inflammation; no bleeding on probing.
- = Bleeding on gentle probing; tissue appears normal.
- = Bleeding on probing and change in color due to inflammation.
- = Bleeding on probing, change in color and slight edema.
- = Bleeding on probing, color change, and obvious edema.
- = Bleeding on probing and spontaneous bleeding, also color change and obvious edema.
Measured: at baseline (before the surgery by one week)
Evaluation of the Sulcus bleeding index (SBI):
it will be described by a number on a scale from 0 to 5 as follows: 0: No inflammation; no bleeding on probing.
- = Bleeding on gentle probing; tissue appears normal.
- = Bleeding on probing and change in color due to inflammation.
- = Bleeding on probing, change in color and slight edema.
- = Bleeding on probing, color change, and obvious edema.
- = Bleeding on probing and spontaneous bleeding, also color change and obvious edema.
Measured: 6 months after the surgery.
Evaluation of the probing depth :
it will be measured from the gingival margin to the depth of the periodontal pocket using a periodontal probe in millimeters.
Measured: at baseline (before the surgery by one week)
Evaluation of the probing depth :
it will be measured from the gingival margin to the depth of the periodontal pocket using a periodontal probe in millimeters.
Measured: 6 months after the surgery.
Evaluation of the clinical attachment level :
it will be measured from the cemento-enamel junction to the depth the periodontal pocket by periodontal probe in millimeters.
Measured: at baseline (before the surgery by one week)
Evaluation of the clinical attachment level :
it will be measured from the cemento-enamel junction to the depth the periodontal pocket by periodontal probe in millimeters.
Measured: 6 months after the surgery.
Evaluation of healing.
it will be evaluated by the Early Healing Index (EHI) on a scale from 1 to 5 as follows:
- = complete flap closure - no fibrin line in the interproximal area.
- = complete flap closure - fine fibrin line in the interproximal area 3= complete flap closure - fibrin clot in the interproximal area.
4 = incomplete flap closure - partial necrosis of the interproximal tissue. 5 = incomplete flap closure - complete necrosis of the interproximaltissue.
Measured: one week after the surgery.
Evaluation of healing.
it will be evaluated by the Early Healing Index (EHI) on a scale from 1 to 5 as follows:
- = complete flap closure - no fibrin line in the interproximal area.
- = complete flap closure - fine fibrin line in the interproximal area 3= complete flap closure - fibrin clot in the interproximal area.
4 = incomplete flap closure - partial necrosis of the interproximal tissue. 5 = incomplete flap closure - complete necrosis of the interproximaltissue.
Measured: two weeks after the surgery.
Secondary outcomes (2)
Radiographic assessment .
On the cone beam computed tomography . Distance from cemento-enamel junction (CEJ) to the bottom of the defect and distance from CEJ to the alveolar bone crest were evaluated. To evaluate the bone fill, fusion was done between baseline image and 6 months post-surgery image. Superimposition was done using OnDemand 3D Dental semi-automatic wizard, by manual registration based on fixed anatomical landmarks followed by automatic registration. The bone fill was measured blindly directly by oral and maxillofacial radiologist.
Measured: at baseline (before the surgery by one week)
Radiographic assessment .
On the cone beam computed tomography . Distance from cemento-enamel junction (CEJ) to the bottom of the defect and distance from CEJ to the alveolar bone crest were evaluated. To evaluate the bone fill, fusion was done between baseline image and 6 months post-surgery image. Superimposition was done using OnDemand 3D Dental semi-automatic wizard, by manual registration based on fixed anatomical landmarks followed by automatic registration. The bone fill was measured blindly directly by oral and maxillofacial radiologist.
Measured: 6 months after the surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2022
- Study start1 Jul 2022
- Primary completion1 Sep 2023
- Study completion1 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Periodontal Bone LossStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roaa Mostafa Esmaiil, Ain Shams University
- Investigators
- Ahmed Amr, Professor, Study director, Ain Shams Universityyasmin El Sayed, lecturer, Study director, Ain Shams UniversityMahmoud Mousa, lecturer, Study director, MSA University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05360511
- Sponsor's protocol ID
- EPO In periodontitis
- Status last verified
- Jan 2024
- First submitted
- 4 Mar 2022
- Last updated
- 16 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bollen CM, Mongardini C, Papaioannou W, Van Steenberghe D, Quirynen M. The effect of a one-stage full-mouth disinfection on different intra-oral niches. Clinical and microbiological observations. J Clin Periodontol. 1998 Jan;25(1):56-66. doi: 10.1111/j.1600-051x.1998.tb02364.x.
PubMed 9477021Aslroosta H, Yaghobee S, Akbari S, Kanounisabet N. The effects of topical erythropoietin on non-surgical treatment of periodontitis: a preliminary study. BMC Oral Health. 2021 May 6;21(1):240. doi: 10.1186/s12903-021-01607-y.
PubMed 33957902Cervellini I, Sacre S, Ghezzi P, Mengozzi M. Erythropoietin does not affect TNF and IL-6 production directly. J Biol Regul Homeost Agents. 2013 Jan-Mar;27(1):189-96.
PubMed 23489698Csifo-Nagy BK, Solyom E, Bognar VL, Nevelits A, Dori F. Efficacy of a new-generation platelet-rich fibrin in the treatment of periodontal intrabony defects: a randomized clinical trial. BMC Oral Health. 2021 Nov 15;21(1):580. doi: 10.1186/s12903-021-01925-1.
PubMed 34781955De Bruyckere T, Eghbali A, Younes F, Cleymaet R, Jacquet W, De Bruyn H, Cosyn J. A 5-year prospective study on regenerative periodontal therapy of infrabony defects using minimally invasive surgery and a collagen-enriched bovine-derived xenograft. Clin Oral Investig. 2018 Apr;22(3):1235-1242. doi: 10.1007/s00784-017-2208-x. Epub 2017 Sep 30.
PubMed 28965250Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.
PubMed 17695343Gemmell E, Marshall RI, Seymour GJ. Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontol 2000. 1997 Jun;14:112-43. doi: 10.1111/j.1600-0757.1997.tb00194.x. No abstract available.
PubMed 9567968Hagi TT, Laugisch O, Ivanovic A, Sculean A. Regenerative periodontal therapy. Quintessence Int. 2014 Mar;45(3):185-92. doi: 10.3290/j.qi.a31203.
PubMed 24570985Hamed S, Bennett CL, Demiot C, Ullmann Y, Teot L, Desmouliere A. Erythropoietin, a novel repurposed drug: an innovative treatment for wound healing in patients with diabetes mellitus. Wound Repair Regen. 2014 Jan-Feb;22(1):23-33. doi: 10.1111/wrr.12135. Epub 2013 Dec 13.
PubMed 24471742Jayakumar A, Rajababu P, Rohini S, Butchibabu K, Naveen A, Reddy PK, Vidyasagar S, Satyanarayana D, Pavan Kumar S. Multi-centre, randomized clinical trial on the efficacy and safety of recombinant human platelet-derived growth factor with beta-tricalcium phosphate in human intra-osseous periodontal defects. J Clin Periodontol. 2011 Feb;38(2):163-72. doi: 10.1111/j.1600-051X.2010.01639.x. Epub 2010 Dec 6.
PubMed 21133980Kantarci A, Van Dyke TE. Lipoxin signaling in neutrophils and their role in periodontal disease. Prostaglandins Leukot Essent Fatty Acids. 2005 Sep-Oct;73(3-4):289-99. doi: 10.1016/j.plefa.2005.05.019.
PubMed 15979867Kou Y, Inaba H, Kato T, Tagashira M, Honma D, Kanda T, Ohtake Y, Amano A. Inflammatory responses of gingival epithelial cells stimulated with Porphyromonas gingivalis vesicles are inhibited by hop-associated polyphenols. J Periodontol. 2008 Jan;79(1):174-80. doi: 10.1902/jop.2008.070364.
PubMed 18166108Matarasso M, Iorio-Siciliano V, Blasi A, Ramaglia L, Salvi GE, Sculean A. Enamel matrix derivative and bone grafts for periodontal regeneration of intrabony defects. A systematic review and meta-analysis. Clin Oral Investig. 2015 Sep;19(7):1581-93. doi: 10.1007/s00784-015-1491-7. Epub 2015 May 27.
PubMed 26008887Page RC, Kornman KS. The pathogenesis of human periodontitis: an introduction. Periodontol 2000. 1997 Jun;14:9-11. doi: 10.1111/j.1600-0757.1997.tb00189.x. No abstract available.
PubMed 9567963Papapanou PN, Tonetti MS. Diagnosis and epidemiology of periodontal osseous lesions. Periodontol 2000. 2000 Feb;22:8-21. doi: 10.1034/j.1600-0757.2000.2220102.x. No abstract available.
PubMed 11276518
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Erythropoietin Gel as an Adjunct to Xenograft in the Surgical Management of Intrabony Periodontal Defects. A Randomized Controlled Clinical Study
- ClinicalTrials.gov ID
- NCT05360511
- Acronym / sponsor ID
- EPO In periodontitis
- Conditions
- Periodontal Bone Loss
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 1 Sep 2023 (actual)
- Study completion
- 1 Oct 2023 (actual)
- First posted
- 4 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to evaluate the use of erythropoietin gel as an adjunct to xenograft in the surgical management of intrabony periodontal defects.
Detailed description
In the periodontal disease there is an interaction of the biofilm with the immune response of the host which results in an imbalance between bacterial virulence and the host defense causing changes in bone and connective tissue homeostasis .
Armitage's 1999 classified periodontitis to either chronic or aggressive . In 2017, the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) classified the periodontal disease using a new staging and grading system. Staging is determining the severity of the disease and the complexity of treatment of the disease, while grading gives additional data about the biological consideration of the disease, such as analyzing the history for the rate of progression and predicting the risk for further progression.
Periodontitis is classified to four stages ranging from Stage I: Initial periodontitis the clinical attachment level (CAL=1-2mm), Stage II: Moderate periodontitis (CAL= 3-4 mm), Stage III: Severe periodontitis and increased potential for tooth loss (<4), and (CAL ≥5mm), Stage IV: Severe periodontitis with increased risk for tooth loss (≥5) and (CAL≥5mm). Grading is determined by the risk factors like smoking, diabetes, and outcomes of scaling and root debridement. Grade A: Low rate of progression (no CAL loss over 5 years), Grade B: Moderate rate of progression (CAL loss<2mm over 5years), and Grade C: High rate of progression (CAL loss ≥2 mm over 5 years) .
The periodontal tissue break down happens because of both the direct effect of the microbial invasion and the indirect effect of the host immune response, this happens when the bacterial invasion results in bacterial products that cross the junctional epithelium which stimulates the host immune response resulting in tissue breakdown .
Pattern of bone destruction in periodontitis can be horizontal or vertical .Horizontal bone loss appears as an even bone destruction leading to a uniform decrease in the bone height in relation to the teeth. Vertical bone loss results in formation of a triangular area of missing bone, known as triangulation. Vertical bone loss could result in angular defects and intrabony pocket formation which become very challenging in treatment.
Treatment of periodontitis is targeting mainly the reduction of bacteria present in the subgingival biofilm. The non-surgical periodontal therapy is done by supragingival scaling and subgingival debridement of the roots using hand or power-driven scalers to eliminate all the deposits such as calculus, plaque and endotoxins
Mechanical instrumentation alone has some limitations especially in areas with deep pocket, areas with bony defects and also ineffective against some bacteria, such as Aggregatibacter actinomycetemcomitans(AA) .Therefore the use of chemotherapeutic agents as adjuncts to mechanical periodontal therapy has been strongly recommended .
Systemic and local antimicrobials are used as adjuncts to the non-surgical periodontal therapy, especially in patients with deep periodontal pockets and aggressive or refractory periodontitis .Also chemotherapeutic agents that target the host immune response result in better clinical effect when used as an adjunct to mechanical periodontal therapy .
According to the recent guidelines of the European Federation of Periodontology (EFP) when the pocket depth is 6mm or more after the non-surgical periodontal therapy with or without adjunctive chemotherapeutic agent, access flap surgery is recommended. Also they recommended treating the residual pockets associated with intrabony defect by periodontal regenerative surgery .
There is a positive correlation between the number of walls present and CAL gain, three-walled intrabony defects have 269% higher chance of >3mm CAL gain in comparison to one-walled defects .
Siciliano et al stated that there is a reduced CAL gain in the non-contained defects .
Different treatment approaches are used for periodontal regeneration such as barrier membranes, autografts, allografts, xenografts, biological agents (i.e. enamel matrix derivatives (EMD)), and growth factors .
The recent guidelines of the (EFP) recommended treatment of intrabony defects by periodontal regenerative surgery .
However, there is limited potential of bone grafts to enhance periodontal regeneration and basically they should be used to ensure space provision since the success of the periodontal regeneration surgery is limited by the available space under the mucoperiosteal flap .
In addition, there are some drawbacks with the use of membrane such as membrane exposure, wound infection and bacterial colonization. So, various biomaterials are tested to be used in combination with bone grafts .
Erythropoietin (EPO) is a hematopoietic hormone and has multiple biological effects. In 2014, Hamed et al showed the role of EPO in epithelial regeneration, healing process and its anti-inflammatory properties. In addition, it was concluded that the topical application of the EPO is a very safe route of administration with no systemic side effects. Also Wang et al in 2017 stated that the EPO upregulated the osteogenesis of the human periodontal mesenchymal stem cells by stimulating the expression of osteogenic genes
According to Zheng et al in 2019 the expression of Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and Osterix (which are transcription proteins that are responsible for osteoblastic differentiation) was verified in the periodontal ligament stem cells treated with EPO which confirms the relationship between EPO and osteogenic differentiation of periodontal ligament stem cells .
In a recent study by Aslroosta et al in 2021, he proved that the local delivery of EPO gel in non-surgical periodontal therapy can improve clinical inflammation and enhance the CAL gain .However, no clinical trials have been conducted to study the effect of EPO gel in the intrabony defects. Therefore the present study will be carried out to evaluate the clinical effect of using the EPO gel as an adjunct to xenograft in the surgical management of intrabony periodontal defects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A (Test group) | Experimental | Drug: particulate xenograft + erythropoietin gel.Group A (Test group): Twelve patients will be subjected to open flap debridement and application of particulate xenograft + erythropoietin gel. |
| Group B (Control group) | Active comparator | Combination Product: particulate xenograftGroup B (Control group): Twelve patients will be subjected to open flap debridement and application of particulate xenograft. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Both genders within age range of 20-50 years.
- Patients diagnosed with periodontitis (Stage III).
- Test site criteria: probing pocket depth ≥6mm and CAL ≥3mm. All these criteria will be determined after phase I conventional periodontal therapy.
- Patients with three-wall intrabony defect.
- Systemically free patients as evidenced by Burket's oral health history questionnaire .
Key exclusion criteria (4 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| particulate xenograft + erythropoietin gel.Also: The mix of xenograft and EPO gel1. Surgical sites will be anaesthetized using local anaesthesia. 2. Intrasulcular incision will be done in the periodontal pocket as close as possible to the tooth surface with the deepest point being the alveolar crest. 3. The incisions will be extended to the mesial papilla of the tooth before the defect and the distal papilla of the tooth after the defect. 4. Both buccal and lingual/palatal mucoperiosteal flaps will be raised using blunt dissection. 5. Mechanical debridement of the infected tissue from the intrabony defect and root debridement will be done using Gracey curettes. * In Group A (test group): Particulate xenograft will be mixed with EPO gel and applied to fill the whole defect. | Drug | Group A (Test group) |
| particulate xenograftAlso: The xenograft alone* All surgeries will be performed by the same operator as follows: 1. Surgical sites will be anaesthetized using local anaesthesia. 2. Intrasulcular incision will be done in the periodontal pocket as close as possible to the tooth surface with the deepest point being the alveolar crest. 3. The incisions will be extended to the mesial papilla of the tooth before the defect and the distal papilla of the tooth after the defect. 4. Both buccal and lingual/palatal mucoperiosteal flaps will be raised using blunt dissection. 5. Mechanical debridement of the infected tissue from the intrabony defect and root debridement will be done using Gracey curettes. * In Group B (control group): Particulate xenograft will be applied to fill the whole defect. | Combination product | Group B (Control group) |
Primary outcome
Evaluation of Plaque index (PI):
Time frame: at baseline (before the surgery by one week)
it will be described by a number on a scale from 0 to 5 as follows: 0 = No plaque.1 = Separate flecks of plaque present at the cervical margin.2 = A thin, continuous band of plaque.3 = A band of plaque wider than 1 mm.4 = Plaque affecting at least 1/3, but not 2/3 of the side of the crown.5 = Plaque affecting 2/3 or more of the side of the crown.
Evaluation of Plaque index (PI):
Time frame: 6 months after the surgery.
it will be described by a number on a scale from 0 to 5 as follows: 0 = No plaque.1 = Separate flecks of plaque present at the cervical margin.2 = A thin, continuous band of plaque.3 = A band of plaque wider than 1 mm.4 = Plaque affecting at least 1/3, but not 2/3 of the side of the crown.5 = Plaque affecting 2/3 or more of the side of the crown.
Evaluation of the Sulcus bleeding index (SBI):
Time frame: at baseline (before the surgery by one week)
it will be described by a number on a scale from 0 to 5 as follows: 0: No inflammation; no bleeding on probing. 1. = Bleeding on gentle probing; tissue appears normal. 2. = Bleeding on probing and change in color due to inflammation. 3. = Bleeding on probing, change in color and slight edema. 4. = Bleeding on probing, color change, and obvious edema. 5. = Bleeding on probing and spontaneous bleeding, also color change and obvious edema.
Evaluation of the Sulcus bleeding index (SBI):
Time frame: 6 months after the surgery.
it will be described by a number on a scale from 0 to 5 as follows: 0: No inflammation; no bleeding on probing. 1. = Bleeding on gentle probing; tissue appears normal. 2. = Bleeding on probing and change in color due to inflammation. 3. = Bleeding on probing, change in color and slight edema. 4. = Bleeding on probing, color change, and obvious edema. 5. = Bleeding on probing and spontaneous bleeding, also color change and obvious edema.
Evaluation of the probing depth :
Time frame: at baseline (before the surgery by one week)
it will be measured from the gingival margin to the depth of the periodontal pocket using a periodontal probe in millimeters.
Evaluation of the probing depth :
Time frame: 6 months after the surgery.
it will be measured from the gingival margin to the depth of the periodontal pocket using a periodontal probe in millimeters.
Evaluation of the clinical attachment level :
Time frame: at baseline (before the surgery by one week)
it will be measured from the cemento-enamel junction to the depth the periodontal pocket by periodontal probe in millimeters.
Evaluation of the clinical attachment level :
Time frame: 6 months after the surgery.
it will be measured from the cemento-enamel junction to the depth the periodontal pocket by periodontal probe in millimeters.
Evaluation of healing.
Time frame: one week after the surgery.
it will be evaluated by the Early Healing Index (EHI) on a scale from 1 to 5 as follows: 1. = complete flap closure - no fibrin line in the interproximal area. 2. = complete flap closure - fine fibrin line in the interproximal area 3= complete flap closure - fibrin clot in the interproximal area. 4 = incomplete flap closure - partial necrosis of the interproximal tissue. 5 = incomplete flap closure - complete necrosis of the interproximaltissue.
Evaluation of healing.
Time frame: two weeks after the surgery.
it will be evaluated by the Early Healing Index (EHI) on a scale from 1 to 5 as follows: 1. = complete flap closure - no fibrin line in the interproximal area. 2. = complete flap closure - fine fibrin line in the interproximal area 3= complete flap closure - fibrin clot in the interproximal area. 4 = incomplete flap closure - partial necrosis of the interproximal tissue. 5 = incomplete flap closure - complete necrosis of the interproximaltissue.
2 secondary outcomes
Radiographic assessment .
Time frame: at baseline (before the surgery by one week)
Radiographic assessment .
Time frame: 6 months after the surgery.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2024.
- Background: PubMed 9477021Bollen CM, Mongardini C, Papaioannou W, Van Steenberghe D, Quirynen M. The effect of a one-stage full-mouth disinfection on different intra-oral niches. Clinical and microbiological observations. J Clin Periodontol. 1998 Jan;25(1):56-66. doi: 10.1111/j.1600-051x.1998.tb02364.x.
- Background: PubMed 33957902Aslroosta H, Yaghobee S, Akbari S, Kanounisabet N. The effects of topical erythropoietin on non-surgical treatment of periodontitis: a preliminary study. BMC Oral Health. 2021 May 6;21(1):240. doi: 10.1186/s12903-021-01607-y.
- Background: PubMed 23489698Cervellini I, Sacre S, Ghezzi P, Mengozzi M. Erythropoietin does not affect TNF and IL-6 production directly. J Biol Regul Homeost Agents. 2013 Jan-Mar;27(1):189-96.
- Background: PubMed 34781955Csifo-Nagy BK, Solyom E, Bognar VL, Nevelits A, Dori F. Efficacy of a new-generation platelet-rich fibrin in the treatment of periodontal intrabony defects: a randomized clinical trial. BMC Oral Health. 2021 Nov 15;21(1):580. doi: 10.1186/s12903-021-01925-1.
- Background: PubMed 28965250De Bruyckere T, Eghbali A, Younes F, Cleymaet R, Jacquet W, De Bruyn H, Cosyn J. A 5-year prospective study on regenerative periodontal therapy of infrabony defects using minimally invasive surgery and a collagen-enriched bovine-derived xenograft. Clin Oral Investig. 2018 Apr;22(3):1235-1242. doi: 10.1007/s00784-017-2208-x. Epub 2017 Sep 30.
- Background: PubMed 17695343Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.
- Background: PubMed 9567968Gemmell E, Marshall RI, Seymour GJ. Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontol 2000. 1997 Jun;14:112-43. doi: 10.1111/j.1600-0757.1997.tb00194.x. No abstract available.
- Background: PubMed 24570985Hagi TT, Laugisch O, Ivanovic A, Sculean A. Regenerative periodontal therapy. Quintessence Int. 2014 Mar;45(3):185-92. doi: 10.3290/j.qi.a31203.
- Background: PubMed 24471742Hamed S, Bennett CL, Demiot C, Ullmann Y, Teot L, Desmouliere A. Erythropoietin, a novel repurposed drug: an innovative treatment for wound healing in patients with diabetes mellitus. Wound Repair Regen. 2014 Jan-Feb;22(1):23-33. doi: 10.1111/wrr.12135. Epub 2013 Dec 13.
- Background: PubMed 21133980Jayakumar A, Rajababu P, Rohini S, Butchibabu K, Naveen A, Reddy PK, Vidyasagar S, Satyanarayana D, Pavan Kumar S. Multi-centre, randomized clinical trial on the efficacy and safety of recombinant human platelet-derived growth factor with beta-tricalcium phosphate in human intra-osseous periodontal defects. J Clin Periodontol. 2011 Feb;38(2):163-72. doi: 10.1111/j.1600-051X.2010.01639.x. Epub 2010 Dec 6.
- Background: PubMed 15979867Kantarci A, Van Dyke TE. Lipoxin signaling in neutrophils and their role in periodontal disease. Prostaglandins Leukot Essent Fatty Acids. 2005 Sep-Oct;73(3-4):289-99. doi: 10.1016/j.plefa.2005.05.019.
- Background: PubMed 18166108Kou Y, Inaba H, Kato T, Tagashira M, Honma D, Kanda T, Ohtake Y, Amano A. Inflammatory responses of gingival epithelial cells stimulated with Porphyromonas gingivalis vesicles are inhibited by hop-associated polyphenols. J Periodontol. 2008 Jan;79(1):174-80. doi: 10.1902/jop.2008.070364.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmed Amr, Professor study director
Ain Shams University
yasmin El Sayed, lecturer study director
Ain Shams University
Mahmoud Mousa, lecturer study director
MSA University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing particulate xenograft + erythropoietin gel. and particulate xenograft in people with Periodontal Bone Loss, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of Plaque index (PI): (time frame: at baseline (before the surgery by one week)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05360511, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2024.