Peri-Implantitis and Peri-implant MucositisNCT06863116
Analysis of HIF-1α, MDA, and GPX4 in Peri-Implant Crevicular Fluid
An observational study of Peri-Implantitis and Peri-implant Mucositis and Hypoxia, run by Ege University at 1 site in Turkey (Türkiye).
Trial summary
Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, are inflammatory conditions that affect the tissues surrounding dental implants. If untreated, these diseases can lead to bone loss and implant failure. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Peri-Implantitis and Peri-implant Mucositis, Hypoxia, Ferroptosis
- How many people
- 45 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 15 May 2023to 16 Jul 2024
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: This study included individuals with at least one dental implant, recruited from the Department of Periodontology, Ege University, Faculty of Dentistry. Participants were selected based on specific eligibility criteria, ensuring that they had an implant functioning for at least one year and no history of systemic diseases or recent periodontal treatments. The study population consisted of individuals diagnosed with peri-implant health, peri-implant mucositis, or peri-implantitis, classified according to clinical and radiographic findings. All participants provided informed consent before sample collection.
Who may be able to join
- Participants must have at least one dental implant functioning for a minimum of one year.
- No history of systemic diseases.
- No periodontal treatments (surgical or non-surgical) in the past six months.
- No use of antibiotics or other medications within the past six months.
Who cannot join
- Systemic diseases, including but not limited to:
- Diabetes mellitus Rheumatoid arthritis Cardiovascular disorders Immunological disorders Mucocutaneous diseases Contagious or communicable diseases
- Medication use, including:
- Immunosuppressants Steroids Non-steroidal anti-inflammatory drugs (NSAIDs) Antiepileptics Calcium channel blockers Beta-blockers Anticoagulants Hormonal contraceptives Nutritional supplements
- Pregnant or lactating women.
- Use of orthodontic appliances or removable partial dentures.
- Poorly maintained implant-supported prostheses that may interfere with peri-implant crevicular fluid collection.
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Ege University, Faculty of Dentistry, Department of Periodontology
Izmir, 35040
About this study
Official title: Peri-Implant Hypoxia as a Potential Barrier Against Ferroptotic Mechanisms During Peri-Implant Diseases
Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, are inflammatory conditions that affect the tissues surrounding dental implants. If untreated, these diseases can lead to bone loss and implant failure. This study investigates whether low oxygen levels (hypoxia) in the peri-implant environment influence ferroptosis, a type of cell death associated with oxidative stress. The research focuses on three key biomarkers: hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA).
A total of 45 participants with 62 dental implants were included in the study. They were divided into three groups: peri-implant health, peri-implant mucositis, and peri-implantitis. Peri-implant crevicular fluid (PICF) samples were collected, and the levels of HIF-1α, GPX-4, and MDA were measured using laboratory tests.
The study aims to determine whether hypoxia affects ferroptosis-related pathways by altering GPX-4 and MDA levels. Understanding these mechanisms could provide new insights into peri-implant disease progression and help develop improved treatment strategies.
Read the detailed description
Peri-implant diseases are characterized by an inflammatory response leading to progressive bone loss around dental implants. While microbial biofilms and host immune responses contribute to disease progression, recent studies have suggested that programmed cell death pathways, including ferroptosis, may also play a role. Ferroptosis is an iron-dependent form of non-apoptotic cell death that is regulated by GPX-4, a key enzyme that prevents lipid peroxidation, and MDA, a biomarker of oxidative damage. Hypoxia, a common feature in peri-implant disease, is known to modulate oxidative stress and inflammatory responses through HIF-1α, but its role in ferroptosis remains unclear.
This cross-sectional study aims to evaluate the relationship between hypoxia and ferroptosis in peri-implant diseases by measuring the levels of HIF-1α, GPX-4, and MDA in peri-implant crevicular fluid (PICF). A total of 45 participants with 62 dental implants were included in the study, categorized into peri-implant health (PH), peri-implant mucositis (PM), and peri-implantitis (PP) groups. PICF samples were collected using standardized paper strips, and biomarker levels were quantified via enzyme-linked immunosorbent assay (ELISA). Statistical analyses, including Kruskal-Wallis and Spearman correlation tests, were performed to assess differences among groups and potential associations between biomarkers.
The findings demonstrated that MDA levels were significantly lower in the peri-implantitis and peri-implant mucositis groups compared to peri-implant health, while GPX-4 levels were elevated in peri-implant mucositis and decreased in peri-implantitis. HIF-1α levels showed no significant differences among groups, but a positive correlation was observed between HIF-1α and GPX-4, suggesting a potential interaction between hypoxia and ferroptotic regulation in peri-implant tissues. These results imply that hypoxic conditions in peri-implant diseases may inhibit ferroptosis by modulating GPX-4 activity and reducing lipid peroxidation.
The study provides novel insights into the pathophysiology of peri-implant diseases, suggesting that the peri-implant microenvironment may exhibit unique regulatory mechanisms affecting ferroptotic pathways. While these findings contribute to our understanding of peri-implant disease pathogenesis, further longitudinal studies are needed to establish causal relationships and explore potential therapeutic strategies targeting hypoxia-ferroptosis interactions.
- Keywords
- Peri-Implantitis, Peri-implant mucositis, Hypoxia, Ferroptosis, Lipid Peroxidation
- Medical subject headings
- Peri-Implantitis, Hypoxia
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 |
|---|---|---|
| Peri-Implant Health | Participants with no clinical signs of peri-implant disease. These individuals exhibit healthy peri-implant soft tissues with no bleeding on probing (BOP), probing depth (PD) ≤ 4 mm, and no radiographic bone loss. | |
| Peri-Implant Mucositis | Participants diagnosed with peri-implant mucositis, characterized by bleeding on probing (BOP) and/or signs of inflammation (redness, swelling), but without radiographic bone loss beyond early remodeling. | |
| Peri-Implantitis | Participants diagnosed with peri-implantitis, defined by increased probing depth (PD > 5 mm), bleeding on probing (BOP) or suppuration, and radiographic evidence of bone loss beyond initial remodeling. |
What is being measured
The primary outcome is the main question the study is designed to answer.
HIF-1α, GPX-4, and MDA Levels in Peri-Implant Crevicular Fluid
Measurement of hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA) levels in peri-implant crevicular fluid using enzyme-linked immunosorbent assay (ELISA) to assess their association with peri-implant health, mucositis, and peri-implantitis.
Measured: Cross-sectional measurement at a single time point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2025
- Study start15 May 2023
- Primary completion15 May 2024
- Study completion16 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Peri-Implantitis and Peri-implant MucositisStudies of the same condition, open and under way.
- More trials run by Ege 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
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ege University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Büşra Yılmaz, Ege University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06863116
- Sponsor's protocol ID
- 23-4.1T/14
- Status last verified
- Mar 2025
- First submitted
- 3 Mar 2025
- Last updated
- 7 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The decision regarding individual participant data (IPD) sharing has not yet been finalized. Factors such as data privacy regulations, institutional policies, and publication plans will be considered before determining whether and to what extent the collected IPD will be shared.
Publications
Gao X, Hu W, Qian D, Bai X, He H, Li L, Sun S. The Mechanisms of Ferroptosis Under Hypoxia. Cell Mol Neurobiol. 2023 Oct;43(7):3329-3341. doi: 10.1007/s10571-023-01388-8. Epub 2023 Jul 17.
PubMed 37458878Hsieh CH, Lin YJ, Chen WL, Huang YC, Chang CW, Cheng FC, Liu RS, Shyu WC. HIF-1alpha triggers long-lasting glutamate excitotoxicity via system xc- in cerebral ischaemia-reperfusion. J Pathol. 2017 Feb;241(3):337-349. doi: 10.1002/path.4838. Epub 2016 Dec 29.
PubMed 27801527Fan Y, Ma L, Fang X, Du S, Mauck J, Loor JJ, Sun X, Jia H, Xu C, Xu Q. Role of hypoxia-inducible-factor-1alpha (HIF-1alpha) in ferroptosis of adipose tissue during ketosis. J Dairy Sci. 2024 Dec;107(12):10611-10627. doi: 10.3168/jds.2024-24822. Epub 2024 Jul 26.
PubMed 39067746Afacan B, Ozturk VO, Pasali C, Bozkurt E, Kose T, Emingil G. Gingival crevicular fluid and salivary HIF-1alpha, VEGF, and TNF-alpha levels in periodontal health and disease. J Periodontol. 2019 Jul;90(7):788-797. doi: 10.1002/JPER.18-0412. Epub 2018 Dec 11.
PubMed 30536725Xing L, Dong W, Chen Y, Dai W, Xiao X, Liu Z, Zhang X, Bai D, Xu H. Fibroblast ferroptosis is involved in periodontitis-induced tissue damage and bone loss. Int Immunopharmacol. 2023 Jan;114:109607. doi: 10.1016/j.intimp.2022.109607. Epub 2022 Dec 22.
PubMed 36700777Qiao S, Li B, Cai Q, Li Z, Yin Z, He J, Li Y, Meng W. Involvement of ferroptosis in Porphyromonas gingivalis lipopolysaccharide-stimulated periodontitis in vitro and in vivo. Oral Dis. 2023 Nov;29(8):3571-3582. doi: 10.1111/odi.14292. Epub 2022 Jul 12.
PubMed 35765229
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peri-Implant Hypoxia as a Potential Barrier Against Ferroptotic Mechanisms During Peri-Implant Diseases
- ClinicalTrials.gov ID
- NCT06863116
- Acronym / sponsor ID
- 23-4.1T/14
- Keywords
- Peri-Implantitis, Peri-implant mucositis, Hypoxia, Ferroptosis, Lipid Peroxidation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Ege UniversityUniversity, hospital or other
- Study start
- 15 May 2023 (actual)
- Primary completion
- 15 May 2024 (actual)
- Study completion
- 16 Jul 2024 (actual)
- First posted
- 7 Mar 2025 (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.
Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, are inflammatory conditions that affect the tissues surrounding dental implants. If untreated, these diseases can lead to bone loss and implant failure. This study investigates whether low oxygen levels (hypoxia) in the peri-implant environment influence ferroptosis, a type of cell death associated with oxidative stress. The research focuses on three key biomarkers: hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA).
A total of 45 participants with 62 dental implants were included in the study. They were divided into three groups: peri-implant health, peri-implant mucositis, and peri-implantitis. Peri-implant crevicular fluid (PICF) samples were collected, and the levels of HIF-1α, GPX-4, and MDA were measured using laboratory tests.
The study aims to determine whether hypoxia affects ferroptosis-related pathways by altering GPX-4 and MDA levels. Understanding these mechanisms could provide new insights into peri-implant disease progression and help develop improved treatment strategies.
Detailed description
Peri-implant diseases are characterized by an inflammatory response leading to progressive bone loss around dental implants. While microbial biofilms and host immune responses contribute to disease progression, recent studies have suggested that programmed cell death pathways, including ferroptosis, may also play a role. Ferroptosis is an iron-dependent form of non-apoptotic cell death that is regulated by GPX-4, a key enzyme that prevents lipid peroxidation, and MDA, a biomarker of oxidative damage. Hypoxia, a common feature in peri-implant disease, is known to modulate oxidative stress and inflammatory responses through HIF-1α, but its role in ferroptosis remains unclear.
This cross-sectional study aims to evaluate the relationship between hypoxia and ferroptosis in peri-implant diseases by measuring the levels of HIF-1α, GPX-4, and MDA in peri-implant crevicular fluid (PICF). A total of 45 participants with 62 dental implants were included in the study, categorized into peri-implant health (PH), peri-implant mucositis (PM), and peri-implantitis (PP) groups. PICF samples were collected using standardized paper strips, and biomarker levels were quantified via enzyme-linked immunosorbent assay (ELISA). Statistical analyses, including Kruskal-Wallis and Spearman correlation tests, were performed to assess differences among groups and potential associations between biomarkers.
The findings demonstrated that MDA levels were significantly lower in the peri-implantitis and peri-implant mucositis groups compared to peri-implant health, while GPX-4 levels were elevated in peri-implant mucositis and decreased in peri-implantitis. HIF-1α levels showed no significant differences among groups, but a positive correlation was observed between HIF-1α and GPX-4, suggesting a potential interaction between hypoxia and ferroptotic regulation in peri-implant tissues. These results imply that hypoxic conditions in peri-implant diseases may inhibit ferroptosis by modulating GPX-4 activity and reducing lipid peroxidation.
The study provides novel insights into the pathophysiology of peri-implant diseases, suggesting that the peri-implant microenvironment may exhibit unique regulatory mechanisms affecting ferroptotic pathways. While these findings contribute to our understanding of peri-implant disease pathogenesis, further longitudinal studies are needed to establish causal relationships and explore potential therapeutic strategies targeting hypoxia-ferroptosis interactions.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Peri-Implant Health | – | –Participants with no clinical signs of peri-implant disease. These individuals exhibit healthy peri-implant soft tissues with no bleeding on probing (BOP), probing depth (PD) ≤ 4 mm, and no radiographic bone loss. |
| Peri-Implant Mucositis | – | –Participants diagnosed with peri-implant mucositis, characterized by bleeding on probing (BOP) and/or signs of inflammation (redness, swelling), but without radiographic bone loss beyond early remodeling. |
| Peri-Implantitis | – | –Participants diagnosed with peri-implantitis, defined by increased probing depth (PD > 5 mm), bleeding on probing (BOP) or suppuration, and radiographic evidence of bone loss beyond initial remodeling. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This study included individuals with at least one dental implant, recruited from the Department of Periodontology, Ege University, Faculty of Dentistry. Participants were selected based on specific eligibility criteria, ensuring that they had an implant functioning for at least one year and no history of systemic diseases or recent periodontal treatments. The study population consisted of individuals diagnosed with peri-implant health, peri-implant mucositis, or peri-implantitis, classified according to clinical and radiographic findings. All participants provided informed consent before sample collection.
Key inclusion criteria (4 listed)
- Participants must have at least one dental implant functioning for a minimum of one year.
- No history of systemic diseases.
- No periodontal treatments (surgical or non-surgical) in the past six months.
- No use of antibiotics or other medications within the past six months.
Key exclusion criteria (7 listed)
- Systemic diseases, including but not limited to:
- Diabetes mellitus Rheumatoid arthritis Cardiovascular disorders Immunological disorders Mucocutaneous diseases Contagious or communicable diseases
- Medication use, including:
- Immunosuppressants Steroids Non-steroidal anti-inflammatory drugs (NSAIDs) Antiepileptics Calcium channel blockers Beta-blockers Anticoagulants Hormonal contraceptives Nutritional supplements
- Pregnant or lactating women.
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
HIF-1α, GPX-4, and MDA Levels in Peri-Implant Crevicular Fluid
Time frame: Cross-sectional measurement at a single time point
Measurement of hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA) levels in peri-implant crevicular fluid using enzyme-linked immunosorbent assay (ELISA) to assess their association with peri-implant health, mucositis, and peri-implantitis.
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 Mar 2025.
- Results publication: PubMed 37458878Gao X, Hu W, Qian D, Bai X, He H, Li L, Sun S. The Mechanisms of Ferroptosis Under Hypoxia. Cell Mol Neurobiol. 2023 Oct;43(7):3329-3341. doi: 10.1007/s10571-023-01388-8. Epub 2023 Jul 17.
- Results publication: PubMed 27801527Hsieh CH, Lin YJ, Chen WL, Huang YC, Chang CW, Cheng FC, Liu RS, Shyu WC. HIF-1alpha triggers long-lasting glutamate excitotoxicity via system xc- in cerebral ischaemia-reperfusion. J Pathol. 2017 Feb;241(3):337-349. doi: 10.1002/path.4838. Epub 2016 Dec 29.
- Results publication: PubMed 39067746Fan Y, Ma L, Fang X, Du S, Mauck J, Loor JJ, Sun X, Jia H, Xu C, Xu Q. Role of hypoxia-inducible-factor-1alpha (HIF-1alpha) in ferroptosis of adipose tissue during ketosis. J Dairy Sci. 2024 Dec;107(12):10611-10627. doi: 10.3168/jds.2024-24822. Epub 2024 Jul 26.
- Results publication: PubMed 30536725Afacan B, Ozturk VO, Pasali C, Bozkurt E, Kose T, Emingil G. Gingival crevicular fluid and salivary HIF-1alpha, VEGF, and TNF-alpha levels in periodontal health and disease. J Periodontol. 2019 Jul;90(7):788-797. doi: 10.1002/JPER.18-0412. Epub 2018 Dec 11.
- Results publication: PubMed 36700777Xing L, Dong W, Chen Y, Dai W, Xiao X, Liu Z, Zhang X, Bai D, Xu H. Fibroblast ferroptosis is involved in periodontitis-induced tissue damage and bone loss. Int Immunopharmacol. 2023 Jan;114:109607. doi: 10.1016/j.intimp.2022.109607. Epub 2022 Dec 22.
- Results publication: PubMed 35765229Qiao S, Li B, Cai Q, Li Z, Yin Z, He J, Li Y, Meng W. Involvement of ferroptosis in Porphyromonas gingivalis lipopolysaccharide-stimulated periodontitis in vitro and in vivo. Oral Dis. 2023 Nov;29(8):3571-3582. doi: 10.1111/odi.14292. Epub 2022 Jul 12.
- Individual participant dataSharing planned: Undecided. The decision regarding individual participant data (IPD) sharing has not yet been finalized. Factors such as data privacy regulations, institutional policies, and publication plans will be considered before determining whether and to what extent the collected IPD 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 Peri-Implantitis and Peri-implant Mucositis and Hypoxia, run by Ege 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 4 inclusion and 7 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 Mar 2025. 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?
HIF-1α, GPX-4, and MDA Levels in Peri-Implant Crevicular Fluid (time frame: Cross-sectional measurement at a single time point). 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 NCT06863116, which also lists 6 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 Mar 2025.