Wound HealNCT04276129
Early Healing of Oral Soft Tissues: a Clinical and Biomolecular Analysis. Part II
A study testing periodontal surgery + 24 hr buccal attached gingiva (G) biopsy and post-surgical CHX mouth-rinses indication in people with Wound Heal and Wound Surgical, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
The purpose of the present study is to evaluate the influence of the post-surgical chlorhexidine indication in the gene expression profile and cellular behavior in the early wound healing process -24 hours after injury- of the oral soft tissues. Read more about this study
- Who is it for?
- Ages 30 to 60 years
- Conditions the study is for
- Wound Heal, Wound Surgical, Oral Soft Tissue Conditions
- What is being tested?
- periodontal surgery + 24 hr buccal attached gingiva (G) biopsy and post-surgical CHX mouth-rinses indication
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteItaly
- Study dates
- 20 Feb 2020to 17 Oct 2020
- Phase
- Interventional
- 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 30 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- patients that required periodontal surgery;
- patients age between 30-60 years;
- patients with full mouth plaque score and full mouth bleeding score < 15%;
- patients with a good general healthy status;
- patients without any medicaments or drug consumption that can affect the healing process;
- non-smoking patients.
Who cannot join
- patients in pregnancy;
- patients in lactation period;
- patients with consumption of antibiotics or anti-inflammatory drugs in the previous six months;
- patients with systemic diseases.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Oral and Maxillofacial Sciences. Section of Periodontics.Sapienza, University of Rome
Roma, 00161
About this study
Official title: Early Healing of Oral Soft Tissues: a Clinical and Biomolecular Analysis. Part II - Effect of Local Chlorhexidine Administration in Gene Expression and Cellular Behaviour 24-hours After Injury
The purpose of the present study is to evaluate the influence of the post-surgical chlorhexidine indication in the gene expression profile and cellular behavior in the early wound healing process -24 hours after injury- of the oral soft tissues.
The main hypothesis is that the post-surgical use of chlorhexidine affects the gene expression and the celular behavior in the early wound healing process of the soft oral tissues.
Read the detailed description
The bacterial infection control in the wound healing is a very important aspect to considerer. Local antiseptic administration after the surgical procedures has been used to control the bacterial contamination.
Chlorhexidine (CHX), widely used as antiseptic, especially as post-surgical indication, has a toxic effect both in vivo and in vitro and their influence on wound healing has been studied for a long time. One of the first animal studies, in 1980, concluded that intensive rinsing with high concentrations of chlorhexidine after oral surgical operations, could result in delay and disturbance of wound healing. Another more recent animal study concluded that CHX induces apoptosis or necrosis in the fibroblasts.
Mariotti and Rumpf, in 2016, carried out a studied incubating human gingival fibroblasts in CHX. The results have been suggested that chlorhexidine could induce a dose dependent reduction in cellular proliferation and that concentrations of chlorhexidine that have little effect on cellular proliferation can significantly reduce both collagen and non-collagen protein production of human gingival fibroblasts in vitro. Hence, the introduction of commercially available concentrations (0.12%) or diluted commercial concentrations (as low as 0.00009%) of chlorhexidine to surgical sites for short periods of time prior to wound closure can conceivably have serious toxic effects on gingival fibroblasts and may negatively affect wound healing.
All the previous mentioned studies permit understand that the CHX is not harmless to the oral tissues. However, its effect is not entirely clear and should be evaluated in depth taking into account that it is one of the most indicated antiseptics after surgery. Currently, there are no studies that evaluate if the post-surgical use of CHX affect the gene expression in the early wound healing.
- Being tested
- periodontal surgery + 24 hr buccal attached gingiva (G) biopsy, post-surgical CHX mouth-rinses indication
- Keywords
- early wound healing, real-time polymerase chain reaction, gingiva, oral mucosa, palatal tissue, Chlorhexidine
- Medical subject headings
- Surgical Wound
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
periodontal surgery + 24 hr buccal attached gingiva (G) biopsyProcedure or surgery
Periodontal surgery will be performed and 24 hr after the surgical procedure a 2mm punch biopsy will be harvested at the level of the buccal attache gingiva (G).
post-surgical CHX mouth-rinses indicationOther
CHX mouth-rinses (0.12%) will be indicated 2 times/day after the surgical procedure
| Study group | Role | What they receive |
|---|---|---|
| post-surgical CHX mouth-rinses (treatment group - CHX) | Experimental | periodontal surgery + post-surgical CHX mouth-rinses + buccal attached gingival (G) biopsies 24 hr after surgical procedure Receives: Procedure: periodontal surgery + 24 hr buccal attached gingiva (G) biopsy; Other: post-surgical CHX mouth-rinses indication |
| NO post-surgical mouth-rinses treatment (non treatment group - NT) | Other | periodontal surgery + buccal attached gingival (G) biopsies 24 hr after surgical procedure Receives: Procedure: periodontal surgery + 24 hr buccal attached gingiva (G) biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline fold regulation wound healing related genes at 24 hours after post-surgical chlorhexidine use.
Total RNA from biopsies or cell cultures was extracted using TRIzol reagent Quantitative real-time PCR (qRT-PCR) cDNA was generated and cDNA obtained were used for amplification of wound healing related genes using the appropriate TaqMan gene expression assay kits.
Measured: 24 hours after surgery (T24)
Secondary outcomes (1)
Clinical evaluation of early wound healing
Assessed with a clinical index (EHS- Early wound healing score). This score assessed clinical signs of re-epithelialization (CSR), clinical signs of haemostasis (CSH), and clinical signs of inflammation (CSI). Since complete wound epithelialization was the main outcome, the CSR score was weighted to be 60% of the total final score. Accordingly, a score of 0, 3, or 6 points was possible for the assessment of CSR, whereas scores of 0, 1, or 2 points were possible for CSH and CSI. Higher values indicated better healing. Accordingly, the score for ideal early wound healing was 10.
Measured: 24 hours after surgery (T24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start20 Feb 2020
- Primary completion17 Oct 2020
- Study completion17 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Wound HealStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe 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
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrea Pilloni MD DDS MS, University of Roma La Sapienza
- Investigators
- Andrea Pilloni, MD,DDS,MS, Study director, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04276129
- Sponsor's protocol ID
- 5315 Prot 1066/19
- Status last verified
- Feb 2021
- First submitted
- 16 Feb 2020
- Last updated
- 1 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014 Dec 3;6(265):265sr6. doi: 10.1126/scitranslmed.3009337.
PubMed 25473038Warburton G, Nares S, Angelov N, Brahim JS, Dionne RA, Wahl SM. Transcriptional events in a clinical model of oral mucosal tissue injury and repair. Wound Repair Regen. 2005 Jan-Feb;13(1):19-26. doi: 10.1111/j.1067-1927.2005.130104.x.
PubMed 15659033Mak K, Manji A, Gallant-Behm C, Wiebe C, Hart DA, Larjava H, Hakkinen L. Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model. J Dermatol Sci. 2009 Dec;56(3):168-80. doi: 10.1016/j.jdermsci.2009.09.005. Epub 2009 Oct 24.
PubMed 19854029Iglesias-Bartolome R, Uchiyama A, Molinolo AA, Abusleme L, Brooks SR, Callejas-Valera JL, Edwards D, Doci C, Asselin-Labat ML, Onaitis MW, Moutsopoulos NM, Gutkind JS, Morasso MI. Transcriptional signature primes human oral mucosa for rapid wound healing. Sci Transl Med. 2018 Jul 25;10(451):eaap8798. doi: 10.1126/scitranslmed.aap8798.
PubMed 30045979Wang Y, Tatakis DN. Human gingiva transcriptome during wound healing. J Clin Periodontol. 2017 Apr;44(4):394-402. doi: 10.1111/jcpe.12669. Epub 2017 Feb 11.
PubMed 28005267Vescarelli E, Pilloni A, Dominici F, Pontecorvi P, Angeloni A, Polimeni A, Ceccarelli S, Marchese C. Autophagy activation is required for myofibroblast differentiation during healing of oral mucosa. J Clin Periodontol. 2017 Oct;44(10):1039-1050. doi: 10.1111/jcpe.12767. Epub 2017 Aug 25.
PubMed 28646601Marini L, Rojas MA, Sahrmann P, Aghazada R, Pilloni A. Early Wound Healing Score: a system to evaluate the early healing of periodontal soft tissue wounds. J Periodontal Implant Sci. 2018 Oct 24;48(5):274-283. doi: 10.5051/jpis.2018.48.5.274. eCollection 2018 Oct.
PubMed 30405935Bassetti C, Kallenberger A. Influence of chlorhexidine rinsing on the healing of oral mucosa and osseous lesions. J Clin Periodontol. 1980 Dec;7(6):443-56. doi: 10.1111/j.1600-051x.1980.tb02151.x.
PubMed 6938525Faria G, Cardoso CR, Larson RE, Silva JS, Rossi MA. Chlorhexidine-induced apoptosis or necrosis in L929 fibroblasts: A role for endoplasmic reticulum stress. Toxicol Appl Pharmacol. 2009 Jan 15;234(2):256-65. doi: 10.1016/j.taap.2008.10.012. Epub 2008 Nov 6.
PubMed 19027770Mariotti AJ, Rumpf DA. Chlorhexidine-induced changes to human gingival fibroblast collagen and non-collagen protein production. J Periodontol. 1999 Dec;70(12):1443-8. doi: 10.1902/jop.1999.70.12.1443.
PubMed 10632519
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Healing of Oral Soft Tissues: a Clinical and Biomolecular Analysis. Part II - Effect of Local Chlorhexidine Administration in Gene Expression and Cellular Behaviour 24-hours After Injury
- ClinicalTrials.gov ID
- NCT04276129
- Acronym / sponsor ID
- 5315 Prot 1066/19
- Keywords
- early wound healing, real-time polymerase chain reaction, gingiva, oral mucosa, palatal tissue, Chlorhexidine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- 20 Feb 2020 (actual)
- Primary completion
- 17 Oct 2020 (actual)
- Study completion
- 17 Oct 2020 (actual)
- First posted
- 19 Feb 2020 (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 purpose of the present study is to evaluate the influence of the post-surgical chlorhexidine indication in the gene expression profile and cellular behavior in the early wound healing process -24 hours after injury- of the oral soft tissues.
The main hypothesis is that the post-surgical use of chlorhexidine affects the gene expression and the celular behavior in the early wound healing process of the soft oral tissues.
Detailed description
The bacterial infection control in the wound healing is a very important aspect to considerer. Local antiseptic administration after the surgical procedures has been used to control the bacterial contamination.
Chlorhexidine (CHX), widely used as antiseptic, especially as post-surgical indication, has a toxic effect both in vivo and in vitro and their influence on wound healing has been studied for a long time. One of the first animal studies, in 1980, concluded that intensive rinsing with high concentrations of chlorhexidine after oral surgical operations, could result in delay and disturbance of wound healing. Another more recent animal study concluded that CHX induces apoptosis or necrosis in the fibroblasts.
Mariotti and Rumpf, in 2016, carried out a studied incubating human gingival fibroblasts in CHX. The results have been suggested that chlorhexidine could induce a dose dependent reduction in cellular proliferation and that concentrations of chlorhexidine that have little effect on cellular proliferation can significantly reduce both collagen and non-collagen protein production of human gingival fibroblasts in vitro. Hence, the introduction of commercially available concentrations (0.12%) or diluted commercial concentrations (as low as 0.00009%) of chlorhexidine to surgical sites for short periods of time prior to wound closure can conceivably have serious toxic effects on gingival fibroblasts and may negatively affect wound healing.
All the previous mentioned studies permit understand that the CHX is not harmless to the oral tissues. However, its effect is not entirely clear and should be evaluated in depth taking into account that it is one of the most indicated antiseptics after surgery. Currently, there are no studies that evaluate if the post-surgical use of CHX affect the gene expression in the early wound healing.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| post-surgical CHX mouth-rinses (treatment group - CHX) | Experimental | Procedure: periodontal surgery + 24 hr buccal attached gingiva (G) biopsy, Other: post-surgical CHX mouth-rinses indicationperiodontal surgery + post-surgical CHX mouth-rinses + buccal attached gingival (G) biopsies 24 hr after surgical procedure |
| NO post-surgical mouth-rinses treatment (non treatment group - NT) | Other | Procedure: periodontal surgery + 24 hr buccal attached gingiva (G) biopsyperiodontal surgery + buccal attached gingival (G) biopsies 24 hr after surgical procedure |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- patients that required periodontal surgery;
- patients age between 30-60 years;
- patients with full mouth plaque score and full mouth bleeding score < 15%;
- patients with a good general healthy status;
- patients without any medicaments or drug consumption that can affect the healing process;
Key exclusion criteria (4 listed)
- patients in pregnancy;
- patients in lactation period;
- patients with consumption of antibiotics or anti-inflammatory drugs in the previous six months;
- patients with systemic diseases.
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 |
|---|---|---|
| periodontal surgery + 24 hr buccal attached gingiva (G) biopsyPeriodontal surgery will be performed and 24 hr after the surgical procedure a 2mm punch biopsy will be harvested at the level of the buccal attache gingiva (G). | Procedure or surgery | NO post-surgical mouth-rinses treatment (non treatment group - NT), post-surgical CHX mouth-rinses (treatment group - CHX) |
| post-surgical CHX mouth-rinses indicationCHX mouth-rinses (0.12%) will be indicated 2 times/day after the surgical procedure | Other | post-surgical CHX mouth-rinses (treatment group - CHX) |
Primary outcome
Changes from baseline fold regulation wound healing related genes at 24 hours after post-surgical chlorhexidine use.
Time frame: 24 hours after surgery (T24)
Total RNA from biopsies or cell cultures was extracted using TRIzol reagent Quantitative real-time PCR (qRT-PCR) cDNA was generated and cDNA obtained were used for amplification of wound healing related genes using the appropriate TaqMan gene expression assay kits.
1 secondary outcome
Clinical evaluation of early wound healing
Time frame: 24 hours after surgery (T24)
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 1 Mar 2021.
- Results publication: PubMed 25473038Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014 Dec 3;6(265):265sr6. doi: 10.1126/scitranslmed.3009337.
- Results publication: PubMed 15659033Warburton G, Nares S, Angelov N, Brahim JS, Dionne RA, Wahl SM. Transcriptional events in a clinical model of oral mucosal tissue injury and repair. Wound Repair Regen. 2005 Jan-Feb;13(1):19-26. doi: 10.1111/j.1067-1927.2005.130104.x.
- Results publication: PubMed 19854029Mak K, Manji A, Gallant-Behm C, Wiebe C, Hart DA, Larjava H, Hakkinen L. Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model. J Dermatol Sci. 2009 Dec;56(3):168-80. doi: 10.1016/j.jdermsci.2009.09.005. Epub 2009 Oct 24.
- Results publication: PubMed 30045979Iglesias-Bartolome R, Uchiyama A, Molinolo AA, Abusleme L, Brooks SR, Callejas-Valera JL, Edwards D, Doci C, Asselin-Labat ML, Onaitis MW, Moutsopoulos NM, Gutkind JS, Morasso MI. Transcriptional signature primes human oral mucosa for rapid wound healing. Sci Transl Med. 2018 Jul 25;10(451):eaap8798. doi: 10.1126/scitranslmed.aap8798.
- Results publication: PubMed 28005267Wang Y, Tatakis DN. Human gingiva transcriptome during wound healing. J Clin Periodontol. 2017 Apr;44(4):394-402. doi: 10.1111/jcpe.12669. Epub 2017 Feb 11.
- Results publication: PubMed 28646601Vescarelli E, Pilloni A, Dominici F, Pontecorvi P, Angeloni A, Polimeni A, Ceccarelli S, Marchese C. Autophagy activation is required for myofibroblast differentiation during healing of oral mucosa. J Clin Periodontol. 2017 Oct;44(10):1039-1050. doi: 10.1111/jcpe.12767. Epub 2017 Aug 25.
- Results publication: PubMed 30405935Marini L, Rojas MA, Sahrmann P, Aghazada R, Pilloni A. Early Wound Healing Score: a system to evaluate the early healing of periodontal soft tissue wounds. J Periodontal Implant Sci. 2018 Oct 24;48(5):274-283. doi: 10.5051/jpis.2018.48.5.274. eCollection 2018 Oct.
- Results publication: PubMed 6938525Bassetti C, Kallenberger A. Influence of chlorhexidine rinsing on the healing of oral mucosa and osseous lesions. J Clin Periodontol. 1980 Dec;7(6):443-56. doi: 10.1111/j.1600-051x.1980.tb02151.x.
- Results publication: PubMed 19027770Faria G, Cardoso CR, Larson RE, Silva JS, Rossi MA. Chlorhexidine-induced apoptosis or necrosis in L929 fibroblasts: A role for endoplasmic reticulum stress. Toxicol Appl Pharmacol. 2009 Jan 15;234(2):256-65. doi: 10.1016/j.taap.2008.10.012. Epub 2008 Nov 6.
- Results publication: PubMed 10632519Mariotti AJ, Rumpf DA. Chlorhexidine-induced changes to human gingival fibroblast collagen and non-collagen protein production. J Periodontol. 1999 Dec;70(12):1443-8. doi: 10.1902/jop.1999.70.12.1443.
- Individual participant dataSharing planned: No
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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.
Andrea Pilloni, MD,DDS,MS study director
University of Roma La Sapienza
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing periodontal surgery + 24 hr buccal attached gingiva (G) biopsy and post-surgical CHX mouth-rinses indication in people with Wound Heal and Wound Surgical, run by University of Roma La Sapienza at 1 site in Italy.
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 1 Mar 2021. 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 Italy. 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.
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?
Changes from baseline fold regulation wound healing related genes at 24 hours after post-surgical chlorhexidine use. (time frame: 24 hours after surgery (T24)). 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 NCT04276129, which also lists 10 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 1 Mar 2021.