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The goal of this clinical trial is to learn if non-surgical periodontal treatment combined with Omega-3 fatty acids and Aspirin can improve clinical outcomes and biochemical markers in patients with periodontitis. The main questions it aims to answer are:
Does the combination of Omega-3 and low-dose Aspirin significantly change the concentration of biochemical and immunological markers such as Interleukin-6 (IL-6) and C-reactive protein (CRP) in serum?
Is the combination of Omega-3 and Aspirin more effective than Omega-3 alone or standard non-surgical treatment in treating periodontitis?
Researchers will compare three groups:
Control group: Scaling and root planing (SRP) only.
Intervention group 1: SRP combined with Omega-3 fatty acids.
Intervention group 2: SRP combined with Omega-3 fatty acids and 81mg Aspirin.
The comparison aims to see if the combined therapy (Intervention group 2) provides superior anti-inflammatory effects and better clinical healing compared to the other groups.
Participants will:
Undergo clinical screening and selection based on study criteria.
Be randomly assigned to one of the three treatment arms.
Receive non-surgical periodontal treatment (scaling and root planing).
Take prescribed supplements (Omega-3 or Omega-3 combined with 81mg Aspirin) according to their assigned group.
Provide blood samples to measure changes in biochemical markers (IL-6, CRP).
Rationale Periodontitis is a chronic inflammatory disease caused by the host's immune response to pathogenic microorganisms, leading to clinical attachment loss and alveolar bone destruction. While non-surgical periodontal therapy (Scaling and Root Planing - SRP) is the gold standard, some patients experience disease progression due to residual subgingival biofilms.
This study explores Host Modulation Therapy (HMT) as an adjunct to SRP. The combination of Omega-3 fatty acids and low-dose Aspirin (81mg) is hypothesized to enhance the resolution of inflammation. Omega-3 serves as a substrate for pro-resolving mediators (Resolvins, Protectins, Maresins), while Aspirin triggers the synthesis of Aspirin-triggered Lipoxins via the COX-2 pathway. This synergistic approach aims to reduce systemic pro-inflammatory markers, specifically Interleukin-6 (IL-6) and C-reactive protein (CRP), and improve clinical healing.
Detailed Study Design This is a randomized controlled clinical trial involving 120 participants. Randomization: Participants who meet the inclusion criteria are randomly assigned to one of three groups (1:1:1 ratio). Randomization is performed using Excel software (RAND function) to generate a random sequence.
Allocation Concealment: Group assignments are placed in sealed, opaque envelopes and managed by a researcher not directly involved in the clinical treatment to ensure unbiased allocation.
Selection and Exclusion Criteria
Inclusion Criteria:
Age ≥ 20 years. Diagnosed with Stage III Periodontitis (Grade B or C) according to the 2017 AAP/EFP classification.
Minimum of 16 natural teeth (excluding third molars and teeth indicated for extraction); at least 6 sites with Probing Pocket Depth (PPD) and Clinical Attachment Loss (CAL) ≥5mm, with bleeding on probing.
No periodontal treatment in the last 3 months; non-smokers
Exclusion Criteria:
Systemic conditions: Mental illness, HIV, autoimmune diseases, chronic hematological, renal, or respiratory diseases, Type 2 diabetes, or obesity.
Pregnancy or breastfeeding. Current use of ≥1g Omega-3/day or anticoagulants (Warfarin, Clopidogrel). History of gastrointestinal bleeding or peptic ulcers; allergy/hypersensitivity to Aspirin or Omega-3.
Intervention Procedures
All participants receive standard non-surgical periodontal therapy, followed by a 30-day supplement regimen:
Non-Surgical Periodontal Treatment (All Groups):
Full-mouth ultrasonic scaling and deep root planing using Gracey curettes. Subgingival irrigation with 0.12% Chlorhexidine. Polishing and oral hygiene instructions (modified Bass technique and interdental cleaning).
Group-Specific Regimens:
Control Group: SRP only (no medicinal supplements). Intervention Group 1: SRP + Omega-3 (Now Foods, 300mg per capsule). Dosage: 4 capsules/day (2 in the morning, 2 in the evening after meals).
Intervention Group 2: SRP + Omega-3 (4 capsules/day) + Aspirin 81mg (Agimexpharm). Dosage: 1 Aspirin tablet/day after breakfast.
Follow-up and Outcome Measures The study includes a long-term follow-up period of 24 months. Participants will return for re-examination at T1 (3 months), T2 (6 months), T3 (12 months), and T4 (24 months).
Clinical Parameters: At each visit, researchers will measure Probing Pocket Depth (PPD), Clinical Attachment Loss (CAL), Full-mouth Plaque Score (FMPS%), Bleeding on Probing (BOP%), and Gingival Index (GI).
Biochemical Evaluation: Venous blood samples will be collected at each time point to quantify serum levels of IL-6 and CRP.
Laboratory Analysis: Serum is separated via centrifugation and stored at -80 °C. IL-6 levels are measured using the Cobas E601 analyzer (electrochemiluminescence immunoassay) at the 108 Military Central Hospital.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SRP only | Active Comparator | Full-mouth ultrasonic scaling and deep root planing using Gracey curettes. Subgingival irrigation with 0.12% Chlorhexidine. Polishing and oral hygiene instructions (modified Bass technique and interdental cleaning). |
|
| SRP + Omega-3 | Experimental | SRP + Omega-3 (Now Foods, 300mg per capsule). Dosage: 4 capsules/day (2 in the morning, 2 in the evening after meals). |
|
| SRP + Omega-3 + Aspirin | Experimental | SRP + Omega-3 (4 capsules/day) + Aspirin 81mg (Agimexpharm). Dosage: 1 Aspirin tablet/day after breakfast. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Scaling and Root Planing (SRP) | Procedure | Full-mouth ultrasonic scaling and deep root planing using Gracey curettes, followed by subgingival irrigation with 0.12% Chlorhexidine. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Probing Pocket Depth (PPD) | Measured as the distance from the gingival margin to the bottom of the periodontal pocket using a William's periodontal probe. Values are reported in millimeters (mm). Higher values indicate deeper pockets and greater periodontal disease severity. | Baseline, 3 months, 6 months, 12 months, and 24 months |
| Serum Interleukin-6 (IL-6) Concentration | Quantification of serum IL-6 levels using the electrochemiluminescence immunoassay (ECLIA) to evaluate systemic anti-inflammatory effects. Values are reported in picograms per milliliter (pg/mL). Higher values indicate higher levels of systemic inflammation. | Baseline, 3 months, 6 months, 12 months, and 24 months |
| Serum C-Reactive Protein (CRP) Concentration | Quantitative assessment of high-sensitivity CRP in serum to monitor the systemic inflammatory response. Values are reported in milligrams per liter (mg/L). Higher values indicate a more significant systemic inflammatory response. | Baseline, 3 months, 6 months, 12 months, and 24 months |
| Modified Gingival Index (MGI) | Assessment of the severity of gingival inflammation using the Modified Gingival Index (MGI) by Lobene. This is a non-invasive index based on visual inspection of the gingiva. The scale for each site ranges from 0 to 4 (0 = Absence of inflammation; 1 = Mild inflammation in any portion of the gingival unit; 2 = Mild inflammation in the entire gingival unit; 3 = Moderate inflammation; 4 = Severe inflammation). The outcome is reported as the mean score of all sites. Total scores range from 0 to 4, where higher scores indicate greater severity of gingival inflammation. | Baseline, 3 months, 6 months, 12 months, and 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Full-mouth Bleeding on Probing (BOP) Percentage | The percentage of sites exhibiting bleeding within 30 seconds after gentle probing. Values range from 0% to 100%. Higher percentages indicate more widespread gingival inflammation and poorer periodontal health. | Baseline, 3 months, 6 months, 12 months, and 24 months |
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Inclusion Criteria:
Age ≥ 20 years. Diagnosed with Stage III Periodontitis (Grade B or C) according to the 2017 AAP/EFP classification.
Minimum of 16 natural teeth (excluding third molars and teeth indicated for extraction); at least 6 sites with Probing Pocket Depth (PPD) and Clinical Attachment Loss (CAL) ≥5mm, with bleeding on probing.
No periodontal treatment in the last 3 months; non-smokers
Exclusion Criteria:
Systemic conditions: Mental illness, HIV, autoimmune diseases, chronic hematological, renal, or respiratory diseases, Type 2 diabetes, or obesity.
Pregnancy or breastfeeding. Current use of ≥1g Omega-3/day or anticoagulants (Warfarin, Clopidogrel). History of gastrointestinal bleeding or peptic ulcers; allergy/hypersensitivity to Aspirin or Omega-3.
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| Name | Affiliation | Role |
|---|---|---|
| Nguyen Ngoc Hoa, PhD | School of Dentistry, Hanoi Medical University, Vietnam | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Stomatology, 108 Military Central Hospital | Hanoi | Hanoi | 11600 | Vietnam |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32613714 | Background | Montero E, Lopez M, Vidal H, Martinez M, Virto L, Marrero J, Herrera D, Zapatero A, Sanz M. Impact of periodontal therapy on systemic markers of inflammation in patients with metabolic syndrome: A randomized clinical trial. Diabetes Obes Metab. 2020 Nov;22(11):2120-2132. doi: 10.1111/dom.14131. Epub 2020 Aug 20. | |
| 36414947 | Background |
| Label | URL |
|---|---|
| Related Info | View source |
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| ID | Term |
|---|---|
| D010518 | Periodontitis |
| ID | Term |
|---|---|
| D010510 | Periodontal Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
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Not provided
| ID | Term |
|---|---|
| D014080 | Tooth Exfoliation |
| D016745 | Root Planing |
| D015525 | Fatty Acids, Omega-3 |
| D001241 | Aspirin |
| ID | Term |
|---|---|
| D009063 | Dental Physiological Phenomena |
| D055688 | Digestive System and Oral Physiological Phenomena |
| D012534 | Dental Scaling |
| D003777 | Dental Prophylaxis |
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This study is designed as a triple-arm, parallel-group randomized controlled trial with a 1:1:1 allocation ratio. The study employs an assessor-blind (single-blind) masking approach to ensure the objectivity of the results.
Key features of the study model include:
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| Omega-3 Fatty Acids | Dietary Supplement | Omega-3 (300mg per capsule: 180mg EPA/120mg DHA). Dosage: 4 capsules/day for 30 days. |
|
| Low-dose aspirin | Drug | 81mg Aspirin (Agimexpharm). Dosage: 1 tablet/day for 30 days. |
|
| Clinical Attachment Loss (CAL) |
Measured as the distance from the cemento-enamel junction (CEJ) to the bottom of the periodontal pocket. Values are reported in millimeters (mm). Higher values indicate greater loss of periodontal attachment and increased disease severity. |
| Baseline, 3 months, 6 months, 12 months, and 24 months |
| Full-mouth Plaque Score (FMPS) | The percentage of tooth surfaces where plaque is present. All teeth are examined at 4 or 6 sites per tooth. The score is calculated as the number of surfaces with plaque divided by the total number of surfaces examined, multiplied by 100. Values range from 0% to 100%, where higher percentages indicate poorer oral hygiene and greater plaque accumulation. | Baseline, 3 months, 6 months, 12 months, and 24 months |
| Lactate Dehydrogenase (LDH) Levels | Quantification of LDH activity in serum as a biomarker for cell death and tissue degradation. Values are reported in Units per Liter (U/L). Higher values indicate increased cell death or tissue damage. | Baseline, 3 months, 6 months, 12 months, and 24 months |
| Maybodi FR, Fakhari M, Tavakoli F. Effects of omega-3 supplementation as an adjunct to non-surgical periodontal therapy on periodontal parameters in periodontitis patients: a randomized clinical trial. BMC Oral Health. 2022 Nov 21;22(1):521. doi: 10.1186/s12903-022-02569-5. |
| 32103495 | Background | Castro Dos Santos NC, Andere NMRB, Araujo CF, de Marco AC, Kantarci A, Van Dyke TE, Santamaria MP. Omega-3 PUFA and aspirin as adjuncts to periodontal debridement in patients with periodontitis and type 2 diabetes mellitus: Randomized clinical trial. J Periodontol. 2020 Oct;91(10):1318-1327. doi: 10.1002/JPER.19-0613. Epub 2020 Jun 21. |
| 41907859 | Background | Benincasa G, Liguori MG, Tarallo F, Saccomanno S, Mancini L, Marchetti E. The role of omega-3 polyunsaturated fatty acids in the non-surgical management of periodontitis: a systematic review and meta-analysis. Front Oral Health. 2026 Mar 13;7:1761032. doi: 10.3389/froh.2026.1761032. eCollection 2026. |
| 39031219 | Background | Savran L, Saglam M. Clinical effects of omega-3 fatty acids supplementation in the periodontal treatment of smokers and non-smokers with periodontitis: a retrospective study. Clin Oral Investig. 2024 Jul 20;28(8):437. doi: 10.1007/s00784-024-05835-8. |
| 37179297 | Background | Stando-Retecka M, Piatek P, Namiecinska M, Bonikowski R, Lewkowicz P, Lewkowicz N. Clinical and microbiological outcomes of subgingival instrumentation supplemented with high-dose omega-3 polyunsaturated fatty acids in periodontal treatment - a randomized clinical trial. BMC Oral Health. 2023 May 13;23(1):290. doi: 10.1186/s12903-023-03018-7. |
| 32383274 | Background | Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Beglundh T, Sculean A, Tonetti MS; EFP Workshop Participants and Methodological Consultants. Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline. J Clin Periodontol. 2020 Jul;47 Suppl 22(Suppl 22):4-60. doi: 10.1111/jcpe.13290. |
| 31143006 | Background | Rampally P, Koduganti RR, Ganapathi SN, Panthula VR, Surya PJ. Comparison of effectiveness of low-dose aspirin versus omega-3 fatty acids as adjuvants to nonsurgical periodontal therapy in Type II diabetic patients with chronic periodontitis. J Indian Soc Periodontol. 2019 May-Jun;23(3):249-256. doi: 10.4103/jisp.jisp_528_18. |
| 32867199 | Background | Stando M, Piatek P, Namiecinska M, Lewkowicz P, Lewkowicz N. Omega-3 Polyunsaturated Fatty Acids EPA and DHA as an Adjunct to Non-Surgical Treatment of Periodontitis: A Randomized Clinical Trial. Nutrients. 2020 Aug 27;12(9):2614. doi: 10.3390/nu12092614. |
| 29926495 | Background | Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Clin Periodontol. 2018 Jun;45 Suppl 20:S149-S161. doi: 10.1111/jcpe.12945. |
| 37345207 | Background | Miroult C, Lasserre J, Toma S. Effects of Omega-3 as an adjuvant in the treatment of periodontal disease: A systematic review and meta-analysis. Clin Exp Dent Res. 2023 Aug;9(4):545-556. doi: 10.1002/cre2.736. Epub 2023 Jun 21. |
| 37787044 | Background | Neprelyuk OA, Zhad'ko SI, Romanenko IG, Kriventsov MA. Adjunctive use of omega-3 fatty acids in combination with low-dose aspirin in periodontitis: Systematic review and meta-analysis. J Periodontal Res. 2023 Dec;58(6):1128-1138. doi: 10.1111/jre.13191. Epub 2023 Oct 3. |
| 39950354 | Background | Araujo CF, Andere NMRB, Castro Dos Santos NC, Ferraz LFF, Miguel MMV, Mathias-Santamaria IF, Monteiro MF, Shaddox LM, Casarin RCV, Santamaria MP. Omega-3 and aspirin in the nonsurgical treatment of grade C periodontitis: A randomized clinical trial. J Periodontol. 2025 Aug;96(8):881-893. doi: 10.1002/JPER.24-0322. Epub 2025 Feb 14. |
| D010517 | Periodontics |
| D003813 | Dentistry |
| D013357 | Subgingival Curettage |
| D011313 | Preventive Dentistry |
| D004042 | Dietary Fats, Unsaturated |
| D004041 | Dietary Fats |
| D005223 | Fats |
| D008055 | Lipids |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D005395 | Fish Oils |
| D009821 | Oils |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |