PeriodontitisNCT07751419
Endoplasmic Reticulum Stress Response in Periodontal Disease
An observational study of Periodontitis and Gingivitis, run by Inonu University at 1 site in Turkey (Türkiye).
Trial summary
Periodontal disease causes inflammation and damage to the tissues that support the teeth. This study looks at whether stress inside gum cells contributes to this damage. Cells have a stress response system that helps them deal with damaged or misfolded proteins. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Periodontitis, Gingivitis
- How many people
- 72 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 15 Sep 2025to 15 Feb 2026
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults aged 18 to 65 years attending the periodontology clinic were enrolled and classified into three groups based on clinical periodontal parameters according to the 2017 World Workshop classification: periodontal health, gingivitis, and periodontitis (Stage III). Exclusion criteria included any systemic disease, regular medication use, smoking, pregnancy or lactation, periodontal treatment within the past 6 months, antibiotic use within the past 6 months, and presence of prosthetic restorations on the teeth to be sampled. A total of 72 participants (24 per group; 36 male, 36 female) were included.
Who may be able to join
- Inclusion criteria for the Healthy Control group were: presence of ≥ 20 teeth in the mouth, probing pocket depth (PPD) ≤ 3 mm, the percentage of bleeding sites for the whole mouth < 10%, and, on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth. Inclusion criteria for the Gingivitis group were: presence of ≥ 20 teeth in the mouth, PPD ≤ 3 mm, % of bleeding sites for the whole mouth ≥ 10%, and, on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth. Inclusion criteria for the Stage 3 Periodontitis group were: presence of ≥ 15 teeth in the mouth, more than 30% of teeth affected by periodontal disease, affected teeth exhibiting probing depths of 6 mm or more and clinical attachment loss (CAL) of ≥ 5 mm, vertical bone loss of 3 mm or more, class 2 or 3 furcation involvement, and radiographic evidence of alveolar bone loss extending to the middle third and beyond (33%) in the relevant teeth
Who cannot join
- Exclusion criteria for all groups were defined as: presence of any systemic disease, regular use of any medication, smoking, pregnancy or lactation, periodontal treatment within the last 6 months, antibiotic use within the last 6 months, and the presence of prosthetic restorations on the teeth to be sampled.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Endoplasmic Reticulum Stress Response in the Pathogenesis of Periodontal Disease
Periodontal disease causes inflammation and damage to the tissues that support the teeth. This study looks at whether stress inside gum cells contributes to this damage. Cells have a stress response system that helps them deal with damaged or misfolded proteins. This study measured several markers of this cell stress response (called GRP78, PERK, IRE1, ATF6, MANF, CRELD2) along with a marker of inflammation (TNF-α). These were measured in fluid collected from around the teeth and in small samples of gum tissue.
Researchers compared 72 healthy adults who did not smoke, divided into three equal groups: people with healthy gums, people with mild gum inflammation (gingivitis), and people with a more advanced form of gum disease (periodontitis). The results showed that markers of cell stress were higher in people with periodontitis compared to the other two groups, both in the fluid around the teeth and in the gum tissue itself. This suggests that cell stress inside gum tissue may play a role in the inflammation and tissue breakdown seen in periodontitis. These findings may help researchers better understand what drives gum disease and could guide future work on new ways to detect or treat it.
Read the detailed description
Periodontal disease will range from gingivitis, a mild and reversible gum inflammation, to periodontitis, a more advanced form that will cause irreversible destruction of the bone and tissue supporting the teeth and may lead to tooth loss if left untreated. A cellular process known as endoplasmic reticulum (ER) stress will be increasingly linked to chronic inflammatory diseases. When cells are exposed to stress, misfolded proteins will accumulate inside the endoplasmic reticulum, and cells will activate a protective mechanism called the unfolded protein response (UPR) to restore normal function. The UPR will operate through three main pathways controlled by the proteins PERK, IRE1, and ATF6. This study will investigate whether markers of ER stress and the UPR, GRP78, PERK, IRE1, ATF6, MANF, and CRELD2 along with the inflammatory marker TNF-α, will be altered in individuals with periodontal disease, and whether these changes will be associated with inflammation severity and tissue destruction. The study will include 72 systemically healthy, non-smoking adults, divided into three equal groups of 24: periodontally healthy individuals, individuals with gingivitis, and individuals with stage III grade B periodontitis. From each participant, gingival crevicular fluid and gingival tissue samples will be collected. Protein levels will be measured using ELISA, and gene expression levels will be assessed using RT-qPCR. In the periodontitis group, total amounts of GRP78, IRE1, PERK, MANF, and CRELD2 in gingival crevicular fluid are expected to be significantly higher, while their concentrations are expected to be lower. Protein levels of IRE1, PERK, MANF, and CRELD2 in gingival tissue, along with gene expression levels of all markers studied, are expected to be significantly elevated. ATF6 is expected to show a distinct pattern, with decreased fluid levels but increased tissue gene expression.
These findings are expected to show that ER stress and UPR pathways will be more active in the gingival tissue of individuals with periodontitis, correlating with inflammation and tissue destruction. This will help researchers identify new biological markers for periodontal disease and support future research into treatments targeting cellular stress pathways.
- Conditions
- Periodontitis, Gingivitis
- Keywords
- endoplasmic reticulum, ER stress, Unfolded Protein Response, Periodontal Inflammation, Gingival Crevicular Fluid, Gingiva
- Medical subject headings
- Periodontitis, Gingivitis
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 |
|---|---|---|
| periodontally healthy | periodontally healthy participants | |
| gingivitis | patients with gingivitis | |
| periodontitis | patients with periodontitis |
What is being measured
The primary outcome is the main question the study is designed to answer.
GCF, Gingival tissue levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α.
Gene expression (RT-PCR, relative fold change via 2^-ΔΔCT method) levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α were measured in gingival tissue samples of participants. Protein levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α in GCF and gingival tissue samples were measured by ELISA in study participants.
Measured: From September 2025 to February 2026
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2026
- Study start15 Sep 2025
- Primary completion15 Feb 2026
- Study completion15 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for PeriodontitisStudies of the same condition, open and under way.
- More trials run by Inonu UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inonu University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kubra Aral, Inonu University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07751419
- Sponsor's protocol ID
- IU-2025-4339
- Status last verified
- Aug 2026
- First submitted
- 3 Aug 2026
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data will be shared, including participant age, sex, and clinical periodontal parameters (plaque index, gingival index, probing depth, clinical attachment level, bleeding on probing). Participants will be identified only by coded/numbered case report forms; no names, gender identity beyond biological sex, or other identifying information will be shared.
Publications
Teles R, Sakellari D, Teles F, Konstantinidis A, Kent R, Socransky S, Haffajee A. Relationships among gingival crevicular fluid biomarkers, clinical parameters of periodontal disease, and the subgingival microbiota. J Periodontol. 2010 Jan;81(1):89-98. doi: 10.1902/jop.2009.090397.
PubMed 20059421Jiang M, Li Z, Zhu G. The role of endoplasmic reticulum stress in the pathophysiology of periodontal disease. J Periodontal Res. 2022 Oct;57(5):915-932. doi: 10.1111/jre.13031. Epub 2022 Jul 12.
PubMed 35818935Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011 Nov 25;334(6059):1081-6. doi: 10.1126/science.1209038.
PubMed 22116877Aral K, Aral CA, Kapila Y. The role of caspase-8, caspase-9, and apoptosis inducing factor in periodontal disease. J Periodontol. 2019 Mar;90(3):288-294. doi: 10.1002/JPER.17-0716. Epub 2018 Oct 26.
PubMed 30311940
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Endoplasmic Reticulum Stress Response in the Pathogenesis of Periodontal Disease
- ClinicalTrials.gov ID
- NCT07751419
- Acronym / sponsor ID
- IU-2025-4339
- Conditions
- Periodontitis, Gingivitis
- Keywords
- endoplasmic reticulum, ER stress, Unfolded Protein Response, Periodontal Inflammation, Gingival Crevicular Fluid, Gingiva
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Inonu UniversityUniversity, hospital or other
- Study start
- 15 Sep 2025 (actual)
- Primary completion
- 15 Feb 2026 (actual)
- Study completion
- 15 Feb 2026 (actual)
- First posted
- 7 Aug 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.
Periodontal disease causes inflammation and damage to the tissues that support the teeth. This study looks at whether stress inside gum cells contributes to this damage. Cells have a stress response system that helps them deal with damaged or misfolded proteins. This study measured several markers of this cell stress response (called GRP78, PERK, IRE1, ATF6, MANF, CRELD2) along with a marker of inflammation (TNF-α). These were measured in fluid collected from around the teeth and in small samples of gum tissue.
Researchers compared 72 healthy adults who did not smoke, divided into three equal groups: people with healthy gums, people with mild gum inflammation (gingivitis), and people with a more advanced form of gum disease (periodontitis). The results showed that markers of cell stress were higher in people with periodontitis compared to the other two groups, both in the fluid around the teeth and in the gum tissue itself. This suggests that cell stress inside gum tissue may play a role in the inflammation and tissue breakdown seen in periodontitis. These findings may help researchers better understand what drives gum disease and could guide future work on new ways to detect or treat it.
Detailed description
Periodontal disease will range from gingivitis, a mild and reversible gum inflammation, to periodontitis, a more advanced form that will cause irreversible destruction of the bone and tissue supporting the teeth and may lead to tooth loss if left untreated. A cellular process known as endoplasmic reticulum (ER) stress will be increasingly linked to chronic inflammatory diseases. When cells are exposed to stress, misfolded proteins will accumulate inside the endoplasmic reticulum, and cells will activate a protective mechanism called the unfolded protein response (UPR) to restore normal function. The UPR will operate through three main pathways controlled by the proteins PERK, IRE1, and ATF6. This study will investigate whether markers of ER stress and the UPR, GRP78, PERK, IRE1, ATF6, MANF, and CRELD2 along with the inflammatory marker TNF-α, will be altered in individuals with periodontal disease, and whether these changes will be associated with inflammation severity and tissue destruction. The study will include 72 systemically healthy, non-smoking adults, divided into three equal groups of 24: periodontally healthy individuals, individuals with gingivitis, and individuals with stage III grade B periodontitis. From each participant, gingival crevicular fluid and gingival tissue samples will be collected. Protein levels will be measured using ELISA, and gene expression levels will be assessed using RT-qPCR. In the periodontitis group, total amounts of GRP78, IRE1, PERK, MANF, and CRELD2 in gingival crevicular fluid are expected to be significantly higher, while their concentrations are expected to be lower. Protein levels of IRE1, PERK, MANF, and CRELD2 in gingival tissue, along with gene expression levels of all markers studied, are expected to be significantly elevated. ATF6 is expected to show a distinct pattern, with decreased fluid levels but increased tissue gene expression.
These findings are expected to show that ER stress and UPR pathways will be more active in the gingival tissue of individuals with periodontitis, correlating with inflammation and tissue destruction. This will help researchers identify new biological markers for periodontal disease and support future research into treatments targeting cellular stress pathways.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| periodontally healthy | – | –periodontally healthy participants |
| gingivitis | – | –patients with gingivitis |
| periodontitis | – | –patients with periodontitis |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adults aged 18 to 65 years attending the periodontology clinic were enrolled and classified into three groups based on clinical periodontal parameters according to the 2017 World Workshop classification: periodontal health, gingivitis, and periodontitis (Stage III). Exclusion criteria included any systemic disease, regular medication use, smoking, pregnancy or lactation, periodontal treatment within the past 6 months, antibiotic use within the past 6 months, and presence of prosthetic restorations on the teeth to be sampled. A total of 72 participants (24 per group; 36 male, 36 female) were included.
Key inclusion criteria (1 listed)
- Inclusion criteria for the Healthy Control group were: presence of ≥ 20 teeth in the mouth, probing pocket depth (PPD) ≤ 3 mm, the percentage of bleeding sites for the whole mouth < 10%, and, on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth. Inclusion criteria for the Gingivitis group were: presence of ≥ 20 teeth in the mouth, PPD ≤ 3 mm, % of bleeding sites for the whole mouth ≥ 10%, and, on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth. Inclusion criteria for the Stage 3 Periodontitis group were: presence of ≥ 15 teeth in the mouth, more than 30% of teeth affected by periodontal disease, affected teeth exhibiting probing depths of 6 mm or more and clinical attachment loss (CAL) of ≥ 5 mm, vertical bone loss of 3 mm or more, class 2 or 3 furcation involvement, and radiographic evidence of alveolar bone loss extending to the middle third and beyond (33%) in the relevant teeth
Key exclusion criteria (1 listed)
- Exclusion criteria for all groups were defined as: presence of any systemic disease, regular use of any medication, smoking, pregnancy or lactation, periodontal treatment within the last 6 months, antibiotic use within the last 6 months, and the presence of prosthetic restorations on the teeth to be sampled.
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
GCF, Gingival tissue levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α.
Time frame: From September 2025 to February 2026
Gene expression (RT-PCR, relative fold change via 2^-ΔΔCT method) levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α were measured in gingival tissue samples of participants. Protein levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α in GCF and gingival tissue samples were measured by ELISA in study participants.
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 7 Aug 2026.
- Background: PubMed 20059421Teles R, Sakellari D, Teles F, Konstantinidis A, Kent R, Socransky S, Haffajee A. Relationships among gingival crevicular fluid biomarkers, clinical parameters of periodontal disease, and the subgingival microbiota. J Periodontol. 2010 Jan;81(1):89-98. doi: 10.1902/jop.2009.090397.
- Background: PubMed 35818935Jiang M, Li Z, Zhu G. The role of endoplasmic reticulum stress in the pathophysiology of periodontal disease. J Periodontal Res. 2022 Oct;57(5):915-932. doi: 10.1111/jre.13031. Epub 2022 Jul 12.
- Background: PubMed 22116877Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011 Nov 25;334(6059):1081-6. doi: 10.1126/science.1209038.
- Background: PubMed 30311940Aral K, Aral CA, Kapila Y. The role of caspase-8, caspase-9, and apoptosis inducing factor in periodontal disease. J Periodontol. 2019 Mar;90(3):288-294. doi: 10.1002/JPER.17-0716. Epub 2018 Oct 26.
- Individual participant dataSharing planned: Yes. De-identified individual participant data will be shared, including participant age, sex, and clinical periodontal parameters (plaque index, gingival index, probing depth, clinical attachment level, bleeding on probing). Participants will be identified only by coded/numbered case report forms; no names, gender identity beyond biological sex, or other identifying information will be shared.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Periodontitis and Gingivitis, run by Inonu University at 1 site in Turkey (Türkiye).
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 1 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: finished, as of the sponsor's last update on 7 Aug 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 Turkey (Türkiye). 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?
GCF, Gingival tissue levels of GRP78, PERK, IRE1, ATF6, MANF, CRELD2, and TNF-α. (time frame: From September 2025 to February 2026). 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 NCT07751419, which also lists 4 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 7 Aug 2026.