Periodontal InflammationNCT07506993
Inflammation in Clear Aligners With and Without Attachments
An observational study of Periodontal Inflammation, run by University of Nebraska at 1 site in United States.
Trial summary
Problem: Clear aligner therapy is widely used in orthodontics due to improved periodontal outcomes compared to fixed appliances. However, composite attachments are frequently bonded to molars to enhance biomechanics, potentially creating plaque-retentive areas that may increase localized inflammatory responses. Read more about this study
- Who is it for?
- Ages 14 to 35 years
- Conditions the study is for
- Periodontal Inflammation
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2026to 1 May 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 14 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Study population will include clear aligner orthodontic patients at the UNMC College of Dentistry aged 14-35 years old.
Who may be able to join
- orthodontic patient at the UNMC College of dentistry
- clear aligner therapy
Who cannot join
- pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Nebraska Medical Center College of Dentistry
Lincoln, Nebraska, 68358
Amy C Killeen, DDS, MS, 402-472-7948, akilleen@unmc.edu
About this study
Official title: Molar-Specific Inflammatory Biomarkers in Adolescents Using Clear Aligners With and Without Attachments
Problem: Clear aligner therapy is widely used in orthodontics due to improved periodontal outcomes compared to fixed appliances. However, composite attachments are frequently bonded to molars to enhance biomechanics, potentially creating plaque-retentive areas that may increase localized inflammatory responses. Currently, no studies have directly compared periodontal inflammatory biomarker levels in molars treated with clear aligners with versus without attachments. This gap limits understanding of the biological impact of attachments on periodontal tissues.Hypothesis:First molars treated with clear aligners and composite attachments will demonstrate higher levels of inflammatory biomarkers in gingival crevicular fluid (GCF) compared to molars treated with clear aligners without attachments. Biomarker levels are expected to be lower in the non-attachment group. Methods: This study will include 30 orthodontic patients divided into two groups (15 per group):1. Clear aligners with molar attachments 2. Clear aligners without molar attachments. GCF samples will be collected from first molars at a routine orthodontic appointment at the UNMC College of Dentistry Graduate Orthodontic Clinic. Primary biomarkers include IL-1β, IL-6, TNF-α, and MMP-8 measured via ELISA. Clinical periodontal parameters (Plaque Index, Gingival Index, Bleeding on Probing, Probing Depth) will also be recorded.
Read the detailed description
Detailed Study Protocol:
This pilot clinical study will recruit subject currently undergoing orthodontic therapy in the graduate orthodontic residency program at the UNMC College of Dentistry. Each subject will be screened for recruitment into the study by review of records by study personnel to determine qualifications regarding inclusion and exclusion criteria. Once the subject has been screened, the subject (if over 18 years old) or the subjects' parent (if subject is between 14-18 years old) will be introduced to the study and invited to participate. The consent form will be reviewed, all questions answered and informed consent obtained prior to data collection. Study groups will consist of 15 subjects per group. Group A will be comprised of 15 subjects undergoing clear aligner orthodontic therapy with bonded composite attachments on the first molars. Group B will be comprised of 15 subjects undergoing clear aligner therapy without attachments on the first molars. The decision whether or not to use aligners is not a study decision and is part of routine orthodontic treatment planning and care. Routine aligner protocol includes a 1 week change schedule (aligner trays are changed/switched weekly) and must be worn a minimum of 22 hours/day. At the single data collection appointment, data collection will include assessment of plaque presence/absence at the mesiobuccal site of the first molars, gingival crevicular fluid (GCF) collection at the mesiobuccal site of the first molars, Gingival Index (Loe \& Silness) assessment at the mesiobuccal of each first molar (visual determination of gingival inflammation), probing depth assessment at the mesiobuccal of each first molar, and bleeding on probing (BOP) assessment at the mesiobuccal of the first molars. These measurements are being done for study purposes only.
The GCF collection procedure includes isolation of the tooth with cotton rolls, followed by gentle removal of all supragingival plaque with a dental explorer instrument. A small paper point will be inserted into the mesiobuccal gingival sulcus and held for 30 seconds to absorb the GCF. Four samples will be taken from each patient, one sample from each first molar. All samples will be stored at -80 degrees Celsius until assay.
Statistical analysis will be completed via t-tests and modeling. Within-patient differences will be calculated by subtracting the inflammatory marker value from a tooth without an attachment from a tooth with an attachment. These differences within patients will be averaged across all patients and compared to a null value of zero using a one sample t-test to see if the difference is statistically significant (this is the same as a paired t-test). This will be done for multiple inflammatory markers of interest, with IL1beta as the primary outcome of interest. As secondary, exploratory analyses, these difference scores will be compared to variables of interest (e.g., age, sex, length of time in a clear aligner, etc.), to see if there are associations with the size of differences observed, using Pearson or Spearman correlations for continuous variables, or Wilcoxon rank sum or Kruskal Wallis test
The primary outcome will be measure of inflammatory biomarker levels in GCF from first molars; specifically IL-1B. IL-6, TNF-alpha, MMP-8 will be measured as secondary outcomes. All biomarkers will be measured in pg/µL.
Additional outcomes will include assessment of periodontal clinical parameters (plaque presence, Gingival index, BOP, probing pocket depth (PD).
- Conditions
- Periodontal Inflammation
- Keywords
- inflammation, orthodontics
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Attachments | Clear aligner with molar attachment users | |
| No attachments | Clear aligners without molar attachment users |
What is being measured
The primary outcome is the main question the study is designed to answer.
IL-1B
Measure of IL-1B at molar sites
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2026
- Study start1 May 2026
- Primary completion31 Dec 2026 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Periodontal InflammationStudies 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amy C. Killeen, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07506993
- Sponsor's protocol ID
- 0171-26-EP
- Status last verified
- Jun 2026
- First submitted
- 20 Mar 2026
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Kredig C, Peuckert E, Schmidtmann I, Drechsler T, Erbe C. Oral health in adolescents: periodontal inflammatory biomarkers during orthodontic clear aligner therapy. Clin Oral Investig. 2025 Mar 5;29(3):168. doi: 10.1007/s00784-025-06212-9.
PubMed 40042542Shokeen B, Viloria E, Duong E, Rizvi M, Murillo G, Mullen J, Shi B, Dinis M, Li H, Tran NC, Lux R, Wu T. The impact of fixed orthodontic appliances and clear aligners on the oral microbiome and the association with clinical parameters: A longitudinal comparative study. Am J Orthod Dentofacial Orthop. 2022 May;161(5):e475-e485. doi: 10.1016/j.ajodo.2021.10.015. Epub 2022 Mar 2.
PubMed 35248417Perinetti G, Paolantonio M, D'Attilio M, D'Archivio D, Tripodi D, Femminella B, Festa F, Spoto G. Alkaline phosphatase activity in gingival crevicular fluid during human orthodontic tooth movement. Am J Orthod Dentofacial Orthop. 2002 Nov;122(5):548-56. doi: 10.1067/mod.2002.126154.
PubMed 12439484Rouzi M, Zhang X, Jiang Q, Long H, Lai W, Li X. Impact of Clear Aligners on Oral Health and Oral Microbiome During Orthodontic Treatment. Int Dent J. 2023 Oct;73(5):603-611. doi: 10.1016/j.identj.2023.03.012. Epub 2023 Apr 25.
PubMed 37105789Xu M, Li G, Tian J, Xie F, Zuo J, Hu J, Yin K, Wang W. Comparison of the effects of clear aligners and fixed appliances on the oral microbiota and reactive oxygen species: a prospective study. Front Cell Infect Microbiol. 2026 Jan 23;15:1738047. doi: 10.3389/fcimb.2025.1738047. eCollection 2025.
PubMed 41659811Sioustis IA, Martu MA, Aminov L, Pavel M, Cianga P, Kappenberg-Nitescu DC, Luchian I, Solomon SM, Martu S. Salivary Metalloproteinase-8 and Metalloproteinase-9 Evaluation in Patients Undergoing Fixed Orthodontic Treatment before and after Periodontal Therapy. Int J Environ Res Public Health. 2021 Feb 8;18(4):1583. doi: 10.3390/ijerph18041583.
PubMed 33567492Kamran MA, Alnazeh AA, Almagbol M, Almoammar S, Alhaizaey AHA, Alshahrani I. Role of six cytokines and bone metabolism biomarkers in gingival crevicular fluid in patients undergoing fixed orthodontic appliance treatment in comparison with aligners: a clinical study. Angle Orthod. 2023 May 1;93(3):335-340. doi: 10.2319/091722-649.1.
PubMed 36807401Gujar AN, Baeshen HA, Alhazmi A, Bhandi S, Raj AT, Patil S, Birkhed D. Cytokine levels in gingival crevicular fluid during orthodontic treatment with aligners compared to conventional labial fixed appliances: a 3-week clinical study. Acta Odontol Scand. 2019 Aug;77(6):474-481. doi: 10.1080/00016357.2019.1607548. Epub 2019 Apr 26.
PubMed 31027423
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molar-Specific Inflammatory Biomarkers in Adolescents Using Clear Aligners With and Without Attachments
- ClinicalTrials.gov ID
- NCT07506993
- Acronym / sponsor ID
- 0171-26-EP
- Conditions
- Periodontal Inflammation
- Keywords
- inflammation, orthodontics
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 1 May 2026 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 2 Apr 2026 (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.
Problem: Clear aligner therapy is widely used in orthodontics due to improved periodontal outcomes compared to fixed appliances. However, composite attachments are frequently bonded to molars to enhance biomechanics, potentially creating plaque-retentive areas that may increase localized inflammatory responses. Currently, no studies have directly compared periodontal inflammatory biomarker levels in molars treated with clear aligners with versus without attachments. This gap limits understanding of the biological impact of attachments on periodontal tissues.Hypothesis:First molars treated with clear aligners and composite attachments will demonstrate higher levels of inflammatory biomarkers in gingival crevicular fluid (GCF) compared to molars treated with clear aligners without attachments. Biomarker levels are expected to be lower in the non-attachment group. Methods: This study will include 30 orthodontic patients divided into two groups (15 per group):1. Clear aligners with molar attachments 2. Clear aligners without molar attachments. GCF samples will be collected from first molars at a routine orthodontic appointment at the UNMC College of Dentistry Graduate Orthodontic Clinic. Primary biomarkers include IL-1β, IL-6, TNF-α, and MMP-8 measured via ELISA. Clinical periodontal parameters (Plaque Index, Gingival Index, Bleeding on Probing, Probing Depth) will also be recorded.
Detailed description
Detailed Study Protocol:
This pilot clinical study will recruit subject currently undergoing orthodontic therapy in the graduate orthodontic residency program at the UNMC College of Dentistry. Each subject will be screened for recruitment into the study by review of records by study personnel to determine qualifications regarding inclusion and exclusion criteria. Once the subject has been screened, the subject (if over 18 years old) or the subjects' parent (if subject is between 14-18 years old) will be introduced to the study and invited to participate. The consent form will be reviewed, all questions answered and informed consent obtained prior to data collection. Study groups will consist of 15 subjects per group. Group A will be comprised of 15 subjects undergoing clear aligner orthodontic therapy with bonded composite attachments on the first molars. Group B will be comprised of 15 subjects undergoing clear aligner therapy without attachments on the first molars. The decision whether or not to use aligners is not a study decision and is part of routine orthodontic treatment planning and care. Routine aligner protocol includes a 1 week change schedule (aligner trays are changed/switched weekly) and must be worn a minimum of 22 hours/day. At the single data collection appointment, data collection will include assessment of plaque presence/absence at the mesiobuccal site of the first molars, gingival crevicular fluid (GCF) collection at the mesiobuccal site of the first molars, Gingival Index (Loe \& Silness) assessment at the mesiobuccal of each first molar (visual determination of gingival inflammation), probing depth assessment at the mesiobuccal of each first molar, and bleeding on probing (BOP) assessment at the mesiobuccal of the first molars. These measurements are being done for study purposes only.
The GCF collection procedure includes isolation of the tooth with cotton rolls, followed by gentle removal of all supragingival plaque with a dental explorer instrument. A small paper point will be inserted into the mesiobuccal gingival sulcus and held for 30 seconds to absorb the GCF. Four samples will be taken from each patient, one sample from each first molar. All samples will be stored at -80 degrees Celsius until assay.
Statistical analysis will be completed via t-tests and modeling. Within-patient differences will be calculated by subtracting the inflammatory marker value from a tooth without an attachment from a tooth with an attachment. These differences within patients will be averaged across all patients and compared to a null value of zero using a one sample t-test to see if the difference is statistically significant (this is the same as a paired t-test). This will be done for multiple inflammatory markers of interest, with IL1beta as the primary outcome of interest. As secondary, exploratory analyses, these difference scores will be compared to variables of interest (e.g., age, sex, length of time in a clear aligner, etc.), to see if there are associations with the size of differences observed, using Pearson or Spearman correlations for continuous variables, or Wilcoxon rank sum or Kruskal Wallis test
The primary outcome will be measure of inflammatory biomarker levels in GCF from first molars; specifically IL-1B. IL-6, TNF-alpha, MMP-8 will be measured as secondary outcomes. All biomarkers will be measured in pg/µL.
Additional outcomes will include assessment of periodontal clinical parameters (plaque presence, Gingival index, BOP, probing pocket depth (PD).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Attachments | – | –Clear aligner with molar attachment users |
| No attachments | – | –Clear aligners without molar attachment users |
Who may qualify
- Ages
- 14 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Study population will include clear aligner orthodontic patients at the UNMC College of Dentistry aged 14-35 years old.
Key inclusion criteria (2 listed)
- orthodontic patient at the UNMC College of dentistry
- clear aligner therapy
Key exclusion criteria (1 listed)
- pregnancy
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
IL-1B
Time frame: Day 1
Measure of IL-1B at molar sites
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Background: PubMed 40042542Kredig C, Peuckert E, Schmidtmann I, Drechsler T, Erbe C. Oral health in adolescents: periodontal inflammatory biomarkers during orthodontic clear aligner therapy. Clin Oral Investig. 2025 Mar 5;29(3):168. doi: 10.1007/s00784-025-06212-9.
- Background: PubMed 35248417Shokeen B, Viloria E, Duong E, Rizvi M, Murillo G, Mullen J, Shi B, Dinis M, Li H, Tran NC, Lux R, Wu T. The impact of fixed orthodontic appliances and clear aligners on the oral microbiome and the association with clinical parameters: A longitudinal comparative study. Am J Orthod Dentofacial Orthop. 2022 May;161(5):e475-e485. doi: 10.1016/j.ajodo.2021.10.015. Epub 2022 Mar 2.
- Background: PubMed 12439484Perinetti G, Paolantonio M, D'Attilio M, D'Archivio D, Tripodi D, Femminella B, Festa F, Spoto G. Alkaline phosphatase activity in gingival crevicular fluid during human orthodontic tooth movement. Am J Orthod Dentofacial Orthop. 2002 Nov;122(5):548-56. doi: 10.1067/mod.2002.126154.
- Background: PubMed 37105789Rouzi M, Zhang X, Jiang Q, Long H, Lai W, Li X. Impact of Clear Aligners on Oral Health and Oral Microbiome During Orthodontic Treatment. Int Dent J. 2023 Oct;73(5):603-611. doi: 10.1016/j.identj.2023.03.012. Epub 2023 Apr 25.
- Background: PubMed 41659811Xu M, Li G, Tian J, Xie F, Zuo J, Hu J, Yin K, Wang W. Comparison of the effects of clear aligners and fixed appliances on the oral microbiota and reactive oxygen species: a prospective study. Front Cell Infect Microbiol. 2026 Jan 23;15:1738047. doi: 10.3389/fcimb.2025.1738047. eCollection 2025.
- Background: PubMed 33567492Sioustis IA, Martu MA, Aminov L, Pavel M, Cianga P, Kappenberg-Nitescu DC, Luchian I, Solomon SM, Martu S. Salivary Metalloproteinase-8 and Metalloproteinase-9 Evaluation in Patients Undergoing Fixed Orthodontic Treatment before and after Periodontal Therapy. Int J Environ Res Public Health. 2021 Feb 8;18(4):1583. doi: 10.3390/ijerph18041583.
- Background: PubMed 36807401Kamran MA, Alnazeh AA, Almagbol M, Almoammar S, Alhaizaey AHA, Alshahrani I. Role of six cytokines and bone metabolism biomarkers in gingival crevicular fluid in patients undergoing fixed orthodontic appliance treatment in comparison with aligners: a clinical study. Angle Orthod. 2023 May 1;93(3):335-340. doi: 10.2319/091722-649.1.
- Background: PubMed 31027423Gujar AN, Baeshen HA, Alhazmi A, Bhandi S, Raj AT, Patil S, Birkhed D. Cytokine levels in gingival crevicular fluid during orthodontic treatment with aligners compared to conventional labial fixed appliances: a 3-week clinical study. Acta Odontol Scand. 2019 Aug;77(6):474-481. doi: 10.1080/00016357.2019.1607548. Epub 2019 Apr 26.
- Individual participant dataSharing planned: Yes
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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.
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 Periodontal Inflammation, run by University of Nebraska 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 1 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: looking for participants now, as of the sponsor's last update on 16 Jun 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amy C Killeen, DDS, MS (402-472-7948, akilleen@unmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IL-1B (time frame: Day 1). 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 NCT07506993, which also lists 8 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 Jun 2026.