Wounds and InjuriesNCT01078467
The Molecular Anatomy of Oral Wound Healing
An observational study of Wounds and Injuries and Wound Healing, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
Trial summary
Background: Two important properties distinguish the healing process of skin wounds from that of wounds of the mucous membranes of the mouth (oral mucosa). Although the skin and the oral mucosa tissues are similar in nature, oral mucosa have more rapid healing and a lack of scar tissue formation. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Wounds and Injuries, Wound Healing, Ulcer
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Feb 2010to 19 Feb 2019
- Phase
- Observational
- 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 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male volunteers age 18 to 40.
- All volunteers must sign informed consent indicating their understanding that specimens and demographic information will be collected solely for research purposes.
Who cannot join
- Subjects with known inflammatory, chronic, and infectious diseases. These conditions include but are not limited to:
- Diabetes
- Heart failure
- Pulmonary disease
- Rheumatoid arthritis
- Systemic lupus erythematosus
Show all 46Show fewer
- Sarcoidosis
- Sj(SqrRoot)(Delta)grens syndrome
- Dermatomyositis
- Psoriasis
- Cellulitis
- Patients with known bleeding disorders or conditions associated with bleeding. These conditions include but are not limited to:
- Hemophilia
- von Willebrand disease
- Protein C/S deficiency
- Antithrombin III deficiency
- Liver disease
- Patients on medications that interfere with blood clotting or blood thinners. These medications include but are not limited to: ibuprofen aspirin, warfarin (Coumadin), ticlopidine (Ticlid), clopidogrel (Plavix), and others.
- Subjects with clinically significant abnormal laboratory values will be ineligible
- Complete blood count (CBC)
- Platelet level: <100 - >500/ 10(3)/mcL<TAB>
- Hemoglobin: <10; > 17.5gr/L<TAB>
- Hematocrit: <30; >51%<TAB>
- White blood cell count: <3; >12 10(3)/mcL
- Partial thromboplastin time: <20; >42 sec
- Prothrombin time: <10; >20 sec
- C-reactive protein: > 4 mg/L
- Erythrocyte sedimentation rate: >40 ml/h
- Recent unintentional weight loss of >10 lbs over the past 6 weeks prior to screening
- Have undergone general or oral surgery within the last 30 days
- Treated with systemic steroids in the past 12 months
- Subjects with a history of abnormal scar formation (i.e., keloids, hypertrophic scarring)
- Subjects who have used tobacco products and/or betel nut within one month of the screening evaluation. Tobacco products include cigarette, pipe, cigar, and chewing tobacco
- Heavy drinkers defined as drinking greater than or equal to alcoholic drinks per day
- Subjects that, at the oral clinical examination, show any of the nonmalignant lesions associated with heavy smoking/tobacco chewing will be excluded. These findings include but are not limited to:
- Tooth stains
- abrasions
- smoker s melanosis
- acute necrotizing gingivitis
- burns
- erythematous or keratotic patches
- black hairy tongue
- nicotinic stomatitis
- palatal erosions
- Subjects with preneoplastic (leukoplakia, erythroplakia, submucous fibrosis) or neoplastic lesions
- Subjects with known or suspected allergies or adverse reactions to any of the agents used for skin preparation, local anesthesia, or pain control or with known or suspected allergy or adverse reaction to Prolene (polypropylene) sutures
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- Two important properties distinguish the healing process of skin wounds from that of wounds of the mucous membranes of the mouth (oral mucosa). Although the skin and the oral mucosa tissues are similar in nature, oral mucosa have more rapid healing and a lack of scar tissue formation. However, oral wound healing in general has been poorly studied, and more information is needed to determine how specific aspects of the oral environment affect the healing process.
- Researchers are interested in identifying various factors that contribute to oral wound healing. Studying this process would help researchers explore procedures to accelerate the healing of critically-sized oral lesions formed by trauma, surgery, radiation therapy, infection, and other damage to the mouth. In addition, research into scar-free healing could be applied to other mucosal sites to promote healing and minimize unsightly scars that may compromise the tissue.
Read more
Objectives:
- To identify the specific factors that enable rapid and nearly scar-free healing of oral mucosa.
Eligibility:
- Healthy male volunteers between 18 and 40 years of age.
- Regular cigarette, cigar, and pipe smokers; occasional smokers who smoke more than 1 day a week or have smoked in the prior month; users of chewing tobacco or betel nut; and heavy drinkers (three or more alcoholic drinks per day) will be excluded.
Design:
- Participants will have a medical history and examination, and will provide blood samples at the start of the study.
- Participants will provide oral mucosa samples from the inside of the cheek, taken using a dermal punch. At the same time, participants will provide skin biopsy samples of approximately the same size. After the skin and oral mucosa samples are taken, participants will be divided into three groups for follow-up procedures.
- Group 1: No further samples will be collected. This group will help document the normal healing process.
- Group 2: A second, slightly larger biopsy, which will include the area of the first biopsy, will be taken on day 3. Both skin and oral mucosa biopsies will be taken.
- Group 3: A second, slightly larger biopsy will be taken on day 6, in a similar way as described for Group 2. Both skin and oral mucosa biopsies will be taken.
- Wounds will be photographed with a digital camera on days 3, 6, 9, 13, and 15; and the healing will be monitored at the scheduled clinic visits.
Read the detailed description
BACKGROUND:
Two important properties distinguish the process of healing of oral mucosa wounds from those of the skin: more rapid healing and the absence of scar tissue formation. This is remarkable given the apparent similarities of the two tissues. There are, however, prominent differences in the healing environment, such as hydration, growth factor availability, inflammatory response, and microbial exposure. Knowledge as to the causal contribution of each of these factors to the differential healing response of the two epithelia is mostly anecdotal, and oral wound healing has generally been poorly studied. This study seeks to provide a global molecular definition of oral wound healing in comparison to that of the skin. The overall aim will be to identify the specific factors that enable rapid and nearly scar-free healing of oral mucosa. Identification of these physiological and molecular determinants will have widespread implications for human oral health. Among others, it would provide venues for the targeted exploration of procedures to accelerate the healing of critically-sized oral lesions formed by trauma, surgery, radiation therapy, infection, and other oral pathologies, which, if untreated, lead to permanent disability and dysfunction. Moreover, pathways and/or molecules identified in these studies which may facilitate rapid, scar-less healing could be considered for application to non-oral mucosal sites to promote healing and minimize unsightly scars, which may also compromise the functional integrity of the tissue.
Hypotheses:
- There are significant differences in gene and protein expression between wound healing in skin and oral mucosa.
- The recruitment of inflammatory cells associated with a large up-regulation of inflammation-associated genes, including cytokines and chemokines, in the epithelial cells of skin wounds may account for these differences.
- There are specific gene programs that can explain the presence of significant scarring in skin tissues but not in oral mucosa.
OBJECTIVES:
The overall objective of this pilot study proposal is to establish the gene and protein expression profiles during the early stages (1-6 days) of normal oral wound repair. By comparing these profiles with those of cutaneous wound healing, we may be able to identify molecules exclusive to oral wound repair that could represent biomarkers of the healing process or serve as new therapeutic targets in pathological wound healing and cancer. One specific hypothesis to be tested is that the level of expression of pro-inflammatory gene networks by wound-infiltrating keratinocytes constitutes the most significant difference between the human oral and cutaneous wound transcriptomes. The specific hypothesis has been developed from data obtained from our recent complementary oral and skin wound healing studies in animals.
ELIGIBILITY:
Healthy male volunteers age 18 to 40 will be enrolled in this study.
DESIGN:
Oral mucosa samples: A sterile 3-mm dermal punch will be used to create uniform, full-thickness biopsy in the mucosa of the cheek just above the occlusal plane. Circular pieces of tissue of approximately 2 mm in depth will be removed on the day of biopsy (day 1). These subjects will be subsequently be randomly grouped as follows:
Group 1: no further samples will be collected; pictures will be taken on days 3, 6, 9, 13, and 15 (see Timetable). This group will help document the normal healing process under the conditions of the present study, including the lack of scaring in the area selected for the initial wound in the oral mucosa as compared with the skin.
Group 2: a second biopsy will be taken on day 3, which will include the area of the first biopsy with sterile 5 mm punch, following the same procedure as described for day 0; pictures will be taken according to the schedule set in the Timetable. This second biopsy will enabled sampling the healing area induced by the first biopsy. By selecting a punch size two millimeters wider and taking a sample concentric to the first one, we can assure complete removal of the area of interest.
Group 3: a second biopsy will be taken on day 6, respectively, in a similar way as described for Group 2; pictures will be taken according to the Timetable.
Skin samples: In parallel to the oral biopsies, skin biopsies of similar size and depth as the oral biopsy from the same subjects will be obtained from the axillary region following the same schedule and procedure, including a second biopsy for groups 2 and 3.
Wounds will be photographed with a digital camera and the healing monitored at clinic visits per schedule above. The excised tissues in each case will be immediately bisected on ice; half of the sample will be fixed in 4% formaldehyde/PBS and embedded in paraffin for standard histology and immunohistochemistry, and the remaining half will be placed in OCT-filled plastic base molds, flash frozen in liquid nitrogen, and stored at 80 (Infinite)C until processed for genomic and proteomic analysis.
- Conditions
- Wounds and Injuries, Wound Healing, Ulcer
- Keywords
- Wound Healing, Oral Wounds, Cutaneous Wounds, Gene Array Analysis, Proteomic Analysis, Healthy Volunteer, HV
- Medical subject headings
- Wounds and Injuries, Ulcer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2010 (estimated)
- Study start2 Feb 2010
- Study completion19 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Wounds and InjuriesStudies of the same condition, open and under way.
- 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Janice S Lee, DDS, MD, Principal investigator, National Institute of Dental and Craniofacial Research (NIDCR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01078467
- Sponsor's protocol ID
- 100020
- Other IDs
- 10-D-0020
- Status last verified
- 19 Feb 2019
- First submitted
- 27 Feb 2010
- Last updated
- 3 Dec 2019
- Results posted
- No
Publications
Schafer M, Werner S. Transcriptional control of wound repair. Annu Rev Cell Dev Biol. 2007;23:69-92. doi: 10.1146/annurev.cellbio.23.090506.123609.
PubMed 17474876Baker H, Patel V, Molinolo AA, Shillitoe EJ, Ensley JF, Yoo GH, Meneses-Garcia A, Myers JN, El-Naggar AK, Gutkind JS, Hancock WS. Proteome-wide analysis of head and neck squamous cell carcinomas using laser-capture microdissection and tandem mass spectrometry. Oral Oncol. 2005 Feb;41(2):183-99. doi: 10.1016/j.oraloncology.2004.08.009.
PubMed 15695121Lee HG, Eun HC. Differences between fibroblasts cultured from oral mucosa and normal skin: implication to wound healing. J Dermatol Sci. 1999 Nov;21(3):176-82. doi: 10.1016/s0923-1811(99)00037-7.
PubMed 10527379
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Molecular Anatomy of Oral Wound Healing
- ClinicalTrials.gov ID
- NCT01078467
- Acronym / sponsor ID
- 100020
- Conditions
- Wounds and Injuries, Wound Healing, Ulcer
- Keywords
- Wound Healing, Oral Wounds, Cutaneous Wounds, Gene Array Analysis, Proteomic Analysis, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)US National Institutes of Health
- Study start
- 2 Feb 2010
- Study completion
- 19 Feb 2019
- First posted
- 2 Mar 2010 (estimated)
- 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.
Background:
- Two important properties distinguish the healing process of skin wounds from that of wounds of the mucous membranes of the mouth (oral mucosa). Although the skin and the oral mucosa tissues are similar in nature, oral mucosa have more rapid healing and a lack of scar tissue formation. However, oral wound healing in general has been poorly studied, and more information is needed to determine how specific aspects of the oral environment affect the healing process.
- Researchers are interested in identifying various factors that contribute to oral wound healing. Studying this process would help researchers explore procedures to accelerate the healing of critically-sized oral lesions formed by trauma, surgery, radiation therapy, infection, and other damage to the mouth. In addition, research into scar-free healing could be applied to other mucosal sites to promote healing and minimize unsightly scars that may compromise the tissue.
Objectives:
- To identify the specific factors that enable rapid and nearly scar-free healing of oral mucosa.
Eligibility:
- Healthy male volunteers between 18 and 40 years of age.
- Regular cigarette, cigar, and pipe smokers; occasional smokers who smoke more than 1 day a week or have smoked in the prior month; users of chewing tobacco or betel nut; and heavy drinkers (three or more alcoholic drinks per day) will be excluded.
Design:
- Participants will have a medical history and examination, and will provide blood samples at the start of the study.
- Participants will provide oral mucosa samples from the inside of the cheek, taken using a dermal punch. At the same time, participants will provide skin biopsy samples of approximately the same size. After the skin and oral mucosa samples are taken, participants will be divided into three groups for follow-up procedures.
- Group 1: No further samples will be collected. This group will help document the normal healing process.
- Group 2: A second, slightly larger biopsy, which will include the area of the first biopsy, will be taken on day 3. Both skin and oral mucosa biopsies will be taken.
- Group 3: A second, slightly larger biopsy will be taken on day 6, in a similar way as described for Group 2. Both skin and oral mucosa biopsies will be taken.
- Wounds will be photographed with a digital camera on days 3, 6, 9, 13, and 15; and the healing will be monitored at the scheduled clinic visits.
Detailed description
BACKGROUND:
Two important properties distinguish the process of healing of oral mucosa wounds from those of the skin: more rapid healing and the absence of scar tissue formation. This is remarkable given the apparent similarities of the two tissues. There are, however, prominent differences in the healing environment, such as hydration, growth factor availability, inflammatory response, and microbial exposure. Knowledge as to the causal contribution of each of these factors to the differential healing response of the two epithelia is mostly anecdotal, and oral wound healing has generally been poorly studied. This study seeks to provide a global molecular definition of oral wound healing in comparison to that of the skin. The overall aim will be to identify the specific factors that enable rapid and nearly scar-free healing of oral mucosa. Identification of these physiological and molecular determinants will have widespread implications for human oral health. Among others, it would provide venues for the targeted exploration of procedures to accelerate the healing of critically-sized oral lesions formed by trauma, surgery, radiation therapy, infection, and other oral pathologies, which, if untreated, lead to permanent disability and dysfunction. Moreover, pathways and/or molecules identified in these studies which may facilitate rapid, scar-less healing could be considered for application to non-oral mucosal sites to promote healing and minimize unsightly scars, which may also compromise the functional integrity of the tissue.
Hypotheses:
- There are significant differences in gene and protein expression between wound healing in skin and oral mucosa.
- The recruitment of inflammatory cells associated with a large up-regulation of inflammation-associated genes, including cytokines and chemokines, in the epithelial cells of skin wounds may account for these differences.
- There are specific gene programs that can explain the presence of significant scarring in skin tissues but not in oral mucosa.
OBJECTIVES:
The overall objective of this pilot study proposal is to establish the gene and protein expression profiles during the early stages (1-6 days) of normal oral wound repair. By comparing these profiles with those of cutaneous wound healing, we may be able to identify molecules exclusive to oral wound repair that could represent biomarkers of the healing process or serve as new therapeutic targets in pathological wound healing and cancer. One specific hypothesis to be tested is that the level of expression of pro-inflammatory gene networks by wound-infiltrating keratinocytes constitutes the most significant difference between the human oral and cutaneous wound transcriptomes. The specific hypothesis has been developed from data obtained from our recent complementary oral and skin wound healing studies in animals.
ELIGIBILITY:
Healthy male volunteers age 18 to 40 will be enrolled in this study.
DESIGN:
Oral mucosa samples: A sterile 3-mm dermal punch will be used to create uniform, full-thickness biopsy in the mucosa of the cheek just above the occlusal plane. Circular pieces of tissue of approximately 2 mm in depth will be removed on the day of biopsy (day 1). These subjects will be subsequently be randomly grouped as follows:
Group 1: no further samples will be collected; pictures will be taken on days 3, 6, 9, 13, and 15 (see Timetable). This group will help document the normal healing process under the conditions of the present study, including the lack of scaring in the area selected for the initial wound in the oral mucosa as compared with the skin.
Group 2: a second biopsy will be taken on day 3, which will include the area of the first biopsy with sterile 5 mm punch, following the same procedure as described for day 0; pictures will be taken according to the schedule set in the Timetable. This second biopsy will enabled sampling the healing area induced by the first biopsy. By selecting a punch size two millimeters wider and taking a sample concentric to the first one, we can assure complete removal of the area of interest.
Group 3: a second biopsy will be taken on day 6, respectively, in a similar way as described for Group 2; pictures will be taken according to the Timetable.
Skin samples: In parallel to the oral biopsies, skin biopsies of similar size and depth as the oral biopsy from the same subjects will be obtained from the axillary region following the same schedule and procedure, including a second biopsy for groups 2 and 3.
Wounds will be photographed with a digital camera and the healing monitored at clinic visits per schedule above. The excised tissues in each case will be immediately bisected on ice; half of the sample will be fixed in 4% formaldehyde/PBS and embedded in paraffin for standard histology and immunohistochemistry, and the remaining half will be placed in OCT-filled plastic base molds, flash frozen in liquid nitrogen, and stored at 80 (Infinite)C until processed for genomic and proteomic analysis.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy male volunteers age 18 to 40.
- All volunteers must sign informed consent indicating their understanding that specimens and demographic information will be collected solely for research purposes.
Key exclusion criteria (46 listed)
- Subjects with known inflammatory, chronic, and infectious diseases. These conditions include but are not limited to:
- Diabetes
- Heart failure
- Pulmonary disease
- Rheumatoid arthritis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 3 Dec 2019.
- Background: PubMed 17474876Schafer M, Werner S. Transcriptional control of wound repair. Annu Rev Cell Dev Biol. 2007;23:69-92. doi: 10.1146/annurev.cellbio.23.090506.123609.
- Background: PubMed 15695121Baker H, Patel V, Molinolo AA, Shillitoe EJ, Ensley JF, Yoo GH, Meneses-Garcia A, Myers JN, El-Naggar AK, Gutkind JS, Hancock WS. Proteome-wide analysis of head and neck squamous cell carcinomas using laser-capture microdissection and tandem mass spectrometry. Oral Oncol. 2005 Feb;41(2):183-99. doi: 10.1016/j.oraloncology.2004.08.009.
- Background: PubMed 10527379Lee HG, Eun HC. Differences between fibroblasts cultured from oral mucosa and normal skin: implication to wound healing. J Dermatol Sci. 1999 Nov;21(3):176-82. doi: 10.1016/s0923-1811(99)00037-7.
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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.
Janice S Lee, DDS, MD principal investigator
National Institute of Dental and Craniofacial Research (NIDCR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Wounds and Injuries and Wound Healing, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
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 2 inclusion and 46 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 3 Dec 2019. 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 United States. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01078467, which also lists 3 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 3 Dec 2019.