Ignite Creation Date:
2024-05-06 @ 9:20 AM
Last Modification Date:
2024-10-26 @ 12:12 PM
Study NCT ID:
NCT02953249
Status:
UNKNOWN
Last Update Posted:
2016-11-02
First Post:
2016-03-21
Brief Title:
Wound Healing After Tooth Extraction in Individuals With Type 1 Diabetes Mellitus
Sponsor:
University of Sao Paulo
Organization:
University of Sao Paulo
Study Overview
Official Title:
Wound Healing After Tooth Extraction in Individuals With Type 1 Diabetes Mellitus
Status:
UNKNOWN
Status Verified Date:
2016-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Dental treatment to individuals with diabetes mellitus particularly type 1 diabetes T1DM has always represented a challenge to the dentist The literature provides some scientific evidence showing that diabetes is a risk factor for the occurrence of oral opportunistic infections abnormal bone metabolism and delay in tissue repair but with varying degrees of evidence
Hyperglycemia as well as diabetes are known as risk factor for post-surgical infections so maintaining the glycemic control in the postoperative period has been standard to health care However there are few studies on the impact of the glycemic control in the repair process after tooth extractions And to our knowledge there arent evidences that infections resulting from oral surgery are more frequent in individuals with diabetes or that the antibiotics prophylaxis is needed for these individuals before invasive dental procedures
Some prospective studies show that people with diabetes especially type 2 T2DM do not exhibit higher frequency of complications in repair process after tooth extractions compared to healthy individuals without diabetes Recently the study conduct by Fernandes et al 2015 found higher frequency of delay on epithelial covering of the alveolus after 21 days of tooth extraction in individuals with T2DM comparing to a control group Delay was not related to infection and on the day 60th after surgery all alveolus were totally epithelized One of the authors hypothesis for the delay in the alveolar epithelialization on the participants with T2DM was the possible reduction of Epithelial Grow Factor EGF in saliva of these individuals Some studies already demonstrated the reduction in salivary detection of EGF in individuals with diabetes
There arent prospective studies in the literature at our disposal that evaluated intraoperative complications of tooth extractions of teeth already erupted in individuals with T1DM or even post tooth extraction healing and the chronology of epithelialization of the alveolus and its relation with the degree of salivary EGF
The aim of this study is to evaluated the intraoperative events and the post- tooth extraction healing regarding the chronology of the repairing events and the occurrence of postoperative complications in individuals with T1DM compared to a control group Besides this study intend to relate the time of complete epithelial covering of the alveolus with the EGF collected by whole stimulated saliva
Hyperglycemia as well as diabetes are known as risk factor for post-surgical infections so maintaining the glycemic control in the postoperative period has been standard to health care However there are few studies on the impact of the glycemic control in the repair process after tooth extractions And to our knowledge there arent evidences that infections resulting from oral surgery are more frequent in individuals with diabetes or that the antibiotics prophylaxis is needed for these individuals before invasive dental procedures
Some prospective studies show that people with diabetes especially type 2 T2DM do not exhibit higher frequency of complications in repair process after tooth extractions compared to healthy individuals without diabetes Recently the study conduct by Fernandes et al 2015 found higher frequency of delay on epithelial covering of the alveolus after 21 days of tooth extraction in individuals with T2DM comparing to a control group Delay was not related to infection and on the day 60th after surgery all alveolus were totally epithelized One of the authors hypothesis for the delay in the alveolar epithelialization on the participants with T2DM was the possible reduction of Epithelial Grow Factor EGF in saliva of these individuals Some studies already demonstrated the reduction in salivary detection of EGF in individuals with diabetes
There arent prospective studies in the literature at our disposal that evaluated intraoperative complications of tooth extractions of teeth already erupted in individuals with T1DM or even post tooth extraction healing and the chronology of epithelialization of the alveolus and its relation with the degree of salivary EGF
The aim of this study is to evaluated the intraoperative events and the post- tooth extraction healing regarding the chronology of the repairing events and the occurrence of postoperative complications in individuals with T1DM compared to a control group Besides this study intend to relate the time of complete epithelial covering of the alveolus with the EGF collected by whole stimulated saliva
Detailed Description:
This prospective longitudinal case-control study will include 30 subjects with type 1 diabetes mellitus who require extraction of 1 or more erupted teeth which will make part of study group SG Other 30 healthy subjects without diabetes mellitus in need of tooth extraction will make part of control group CG The groups will be matched by gender and age
This project will be submitted to the Research and Ethics Committee of Dentistry College in University of Sao Paulo and all participants will sign a Consent Term
All subjects who agreed to participate of this research will sign the Consent Term A questionnaire will be filled by the researcher through information obtained by direct questioning of the participant contaning demographic data gender age medical history dental history medications and other health problems
After anamnesis the researcher will make a clinical evaluation of oral health to see the necessity of tooth extractions If there is any indication of tooth extraction a periapical radiograph will be performed Also will be required complimentary blood exams with blood count fasting glycemia and coagulation factors Subjects that will be in use or that made use antibiotics at least a month before the tooth extraction will be excluded from this study
On the day of the surgical procedure will be measured in the individuals of SG quick exams of glicated hemoglobin A1C through the equipment A1C Now Multi-Test HbA1c System Bayer The glycaemia will be measured with the equipment Accu-Check before and after the tooth extraction and in each appointment of post-surgery Day 3 Day 7 Day 21 Day 60 The blood pressure will also be measured before and after the tooth extraction
The saliva collection will be performed before the surgical procedure at least one hour after the patient has fed It will be collected stimulated saliva through the chewing of parafilm In the first minute the patient only will normally chew and swallow saliva in the next five minutes all saliva produced will be deposited in a graduated Falcon tube Salivary flow is going to be measured and expressed in mililiters per minute The collected saliva will centrifuged at 14000 rpm for 15 minutes The supernatant will be collected and freeze at -80oC and the sediment content will be discarded
The saliva analysis for measuring the concentration of EGF will be carried out by immunoassay using an EGF ELISA kit Novex The EGF concentration is expressed by the optical density reading of the samples compared to a standard curve with the aid of a microplate reader with an absorption of 450nm followed by 570nm wavelength
The Invitrogen human EGF kit is a solid phase sandwich Enzyme Linked-Immuno-Sorbent Assay ELISA A polyclonal antibody specific for human EGF has been coated onto the wells of the microtiter strips provided Samples including standards of known human EGF content control specimens and unknowns are pipetted into these wells
During the first incubation the Hu EGF antigen binds to the immobilized capture antibody on one site After washing a biotinylated monoclonal antibody specific for Hu EGF is added During the second incubation this antibody binds to the immobilized Hu EGF captured during the first incubation
After removal of excess second antibody Streptavidin-Peroxidase enzyme is added This binds to the biotinylated antibody to complete the four-member sandwich After a third incubation and washing to remove all the unbound enzyme a substrate solution is added which is acted upon by the bound enzyme to produce color The intensity of this colored product is directly proportional to the concentration of Hu EGF present in the original specimen
On the same day after measuring blood pressure glycaemia and A1C and saliva collection the tooth extraction will be performed No antibiotics will be prescribed before or after surgery as prophylactic function Individuals of SG will be oriented to feed and administer insulin normally Subjects with abnormal laboratorial exams or abnormal glycaemia under 70 or above 400 will re-evaluated and the tooth extraction post-pone
The tooth extractions will be performed by the same dentist with experience in minor oral surgery in the Special Care dentistry center of the Dental School of University of Sao Paulo The subjects of both groups who agreeded to participate will be submitted by conventional extraction technique which is the same technique for any other patient of the Center The participants will receive the same intervention of tooth extraction of patients who are not enrolled in the study as following after the anesthetic block will be held sindesmotomy taking off the periodontal tooth dislocation with the aid of lifts and removal of the tooth with forceps The surgical technique will be modified depending on the condition of the tooth in the alveolus performing dental section or osteotomy when necessary Finally curettage of the socket will be held and a simple suture with silk thread 3-0
At the end of surgery the blood pressure and glycaemia will be measured again Information of the surgery procedure will be recorded such as the tooth that was extracted the reason of tooth was extracted caries periodontal disease orthodontic needed time spent on the surgery number of anesthetic tubes and complications
It will be asked for the participants to press with a gauze the alveolar region for 30 minutes to control bleeding It will be prescript only analgesic every 8 hours for 3 days in case of pain The participant will receive postoperative written instructions
Evaluation of repair and possible complications of the surgical wound will be held in 4 different moments on day 3 7 21 and 60 after surgery These evaluation it will always be perform by the researcher trained and calibrated Will be observed signs and symptoms such as edema erythema bone exposure fever pain and analgesic need Glycaemia will be measured in all appointments from individuals from SG Digitalized periapical radiograph will be performed at the days 7 and 60
The repair process will be considered late when the following events do not match the period considered normal day 3- alveolus filled by blood clot and fibrin day 7- alveolus filled with granulation tissue day 21- complete epithelialization of the wound day 60- alveolus exhibiting bone deposition radiographically observed In case of delay in complete epithelialization after day 21 the subject will be accompanied by further consultations every 7 days for evaluation If there is a delay in the alveolar bone deposition in the day 60 the subject will undergo another monitoring at day 90 for new radiography and evaluation
In case of post-extraction infection alveolitis will set up the recommended treatment described by Kaya et al 2011 with removal of infected debris with abundant irrigation with saline 09 NaCl and curettage It will also be prescribed antibiotics Amoxicilin 500mg or Clindamicin 300mg every 8 hours for 7 days and anti-inflammatory Nimesulide 100mg every 12 hours for 5 days Barasch et al 2008
The pain will be evaluated and assessed at the time of each appointment through the Visual Analogue Scale VAS that consists of direct questioning to the patient and a visual demonstration of the scale Annex A being zero the total absence of pain and ten the maximum bearable level of pain by the patient
After 60 days of surgery the post-operative will be classified as without complications or with complications according to the presence or absence of signs and clinical symptoms observed It will also be classified in without delay and delay according to the chronology of repair observed According to Cheung et al 2001 the following situations will be considered as post-operative complications
Acute alveolar infection characterized by pain erythema edema purulent secretion and fever
Acute inflammation of the alveolus characterized by pain inflammation perialveolar tissue but without purulent secretion and no fever
Alveolitis characterized by persistent throbbing pain and bone exposure All data will be transferred to an Excel spreadsheet and analyzed descriptively and associated with each other Complications will be compared between the two groups Additionally in the study group we will investigate if the occurrence of complications was related to A1C glycaemia at surgery day as well as EGF of saliva
Will be held in all subjects SG and CG at least 3 periapical radiographs through paralleling technique for each tooth requiring extraction The first radiograph will be performed at the time of anamnesis with conventional radiographic film in order to diagnose the need for extraction and assess the condition of the tooth The second and third radiographs will be carried out using a digital sensor at day 7 and day 60 using the digital device Soredex DIGORA Optime to evaluate the alveolar bone repair by grayscale concentration captured
For standardization of these 3 X-rays of the same tooth in the same subject a bite record of each subject will be carried out with silicone and will always be used to take the radiograph The alveolus will be considered repaired and without delay when at the day 60 show complete bone deposition
This project will be submitted to the Research and Ethics Committee of Dentistry College in University of Sao Paulo and all participants will sign a Consent Term
All subjects who agreed to participate of this research will sign the Consent Term A questionnaire will be filled by the researcher through information obtained by direct questioning of the participant contaning demographic data gender age medical history dental history medications and other health problems
After anamnesis the researcher will make a clinical evaluation of oral health to see the necessity of tooth extractions If there is any indication of tooth extraction a periapical radiograph will be performed Also will be required complimentary blood exams with blood count fasting glycemia and coagulation factors Subjects that will be in use or that made use antibiotics at least a month before the tooth extraction will be excluded from this study
On the day of the surgical procedure will be measured in the individuals of SG quick exams of glicated hemoglobin A1C through the equipment A1C Now Multi-Test HbA1c System Bayer The glycaemia will be measured with the equipment Accu-Check before and after the tooth extraction and in each appointment of post-surgery Day 3 Day 7 Day 21 Day 60 The blood pressure will also be measured before and after the tooth extraction
The saliva collection will be performed before the surgical procedure at least one hour after the patient has fed It will be collected stimulated saliva through the chewing of parafilm In the first minute the patient only will normally chew and swallow saliva in the next five minutes all saliva produced will be deposited in a graduated Falcon tube Salivary flow is going to be measured and expressed in mililiters per minute The collected saliva will centrifuged at 14000 rpm for 15 minutes The supernatant will be collected and freeze at -80oC and the sediment content will be discarded
The saliva analysis for measuring the concentration of EGF will be carried out by immunoassay using an EGF ELISA kit Novex The EGF concentration is expressed by the optical density reading of the samples compared to a standard curve with the aid of a microplate reader with an absorption of 450nm followed by 570nm wavelength
The Invitrogen human EGF kit is a solid phase sandwich Enzyme Linked-Immuno-Sorbent Assay ELISA A polyclonal antibody specific for human EGF has been coated onto the wells of the microtiter strips provided Samples including standards of known human EGF content control specimens and unknowns are pipetted into these wells
During the first incubation the Hu EGF antigen binds to the immobilized capture antibody on one site After washing a biotinylated monoclonal antibody specific for Hu EGF is added During the second incubation this antibody binds to the immobilized Hu EGF captured during the first incubation
After removal of excess second antibody Streptavidin-Peroxidase enzyme is added This binds to the biotinylated antibody to complete the four-member sandwich After a third incubation and washing to remove all the unbound enzyme a substrate solution is added which is acted upon by the bound enzyme to produce color The intensity of this colored product is directly proportional to the concentration of Hu EGF present in the original specimen
On the same day after measuring blood pressure glycaemia and A1C and saliva collection the tooth extraction will be performed No antibiotics will be prescribed before or after surgery as prophylactic function Individuals of SG will be oriented to feed and administer insulin normally Subjects with abnormal laboratorial exams or abnormal glycaemia under 70 or above 400 will re-evaluated and the tooth extraction post-pone
The tooth extractions will be performed by the same dentist with experience in minor oral surgery in the Special Care dentistry center of the Dental School of University of Sao Paulo The subjects of both groups who agreeded to participate will be submitted by conventional extraction technique which is the same technique for any other patient of the Center The participants will receive the same intervention of tooth extraction of patients who are not enrolled in the study as following after the anesthetic block will be held sindesmotomy taking off the periodontal tooth dislocation with the aid of lifts and removal of the tooth with forceps The surgical technique will be modified depending on the condition of the tooth in the alveolus performing dental section or osteotomy when necessary Finally curettage of the socket will be held and a simple suture with silk thread 3-0
At the end of surgery the blood pressure and glycaemia will be measured again Information of the surgery procedure will be recorded such as the tooth that was extracted the reason of tooth was extracted caries periodontal disease orthodontic needed time spent on the surgery number of anesthetic tubes and complications
It will be asked for the participants to press with a gauze the alveolar region for 30 minutes to control bleeding It will be prescript only analgesic every 8 hours for 3 days in case of pain The participant will receive postoperative written instructions
Evaluation of repair and possible complications of the surgical wound will be held in 4 different moments on day 3 7 21 and 60 after surgery These evaluation it will always be perform by the researcher trained and calibrated Will be observed signs and symptoms such as edema erythema bone exposure fever pain and analgesic need Glycaemia will be measured in all appointments from individuals from SG Digitalized periapical radiograph will be performed at the days 7 and 60
The repair process will be considered late when the following events do not match the period considered normal day 3- alveolus filled by blood clot and fibrin day 7- alveolus filled with granulation tissue day 21- complete epithelialization of the wound day 60- alveolus exhibiting bone deposition radiographically observed In case of delay in complete epithelialization after day 21 the subject will be accompanied by further consultations every 7 days for evaluation If there is a delay in the alveolar bone deposition in the day 60 the subject will undergo another monitoring at day 90 for new radiography and evaluation
In case of post-extraction infection alveolitis will set up the recommended treatment described by Kaya et al 2011 with removal of infected debris with abundant irrigation with saline 09 NaCl and curettage It will also be prescribed antibiotics Amoxicilin 500mg or Clindamicin 300mg every 8 hours for 7 days and anti-inflammatory Nimesulide 100mg every 12 hours for 5 days Barasch et al 2008
The pain will be evaluated and assessed at the time of each appointment through the Visual Analogue Scale VAS that consists of direct questioning to the patient and a visual demonstration of the scale Annex A being zero the total absence of pain and ten the maximum bearable level of pain by the patient
After 60 days of surgery the post-operative will be classified as without complications or with complications according to the presence or absence of signs and clinical symptoms observed It will also be classified in without delay and delay according to the chronology of repair observed According to Cheung et al 2001 the following situations will be considered as post-operative complications
Acute alveolar infection characterized by pain erythema edema purulent secretion and fever
Acute inflammation of the alveolus characterized by pain inflammation perialveolar tissue but without purulent secretion and no fever
Alveolitis characterized by persistent throbbing pain and bone exposure All data will be transferred to an Excel spreadsheet and analyzed descriptively and associated with each other Complications will be compared between the two groups Additionally in the study group we will investigate if the occurrence of complications was related to A1C glycaemia at surgery day as well as EGF of saliva
Will be held in all subjects SG and CG at least 3 periapical radiographs through paralleling technique for each tooth requiring extraction The first radiograph will be performed at the time of anamnesis with conventional radiographic film in order to diagnose the need for extraction and assess the condition of the tooth The second and third radiographs will be carried out using a digital sensor at day 7 and day 60 using the digital device Soredex DIGORA Optime to evaluate the alveolar bone repair by grayscale concentration captured
For standardization of these 3 X-rays of the same tooth in the same subject a bite record of each subject will be carried out with silicone and will always be used to take the radiograph The alveolus will be considered repaired and without delay when at the day 60 show complete bone deposition
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None