The Effects of DHA on Periodontitis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether docosahexaenoic acid (DHA) is effective in the treatment of periodontitis in adults.

Detailed Description
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The primary aim of this study is to investigate the effect of docosahexaenoic acid (DHA; 2 gm/day) plus low dose aspirin (ASA 81 mg/day)compared to ASA alone on periodontitis over three months. Our hypothesis is that DHA plus ASA will improve periodontitis as measured by objective periodontal exam, including decreased pocket depth (mm), gingival index (0-3), plaque index (0-3) and bleeding on probing (yes/no) compared to ASA alone. Assess the effect of DHA and ASA exposure on markers of local inflammation, including gingival crevicular fluid (GCF) CRP, IL-1 beta and IL-6 three months after exposure to DHA plus ASA compared to ASA alone. Evaluate potential mechanisms through changes in the periodontal microbial flora which may occur as a result of exposure to DHA and ASA compared to ASA alone. Our hypothesis is that there will be a substantial post therapy change in the microbial flora of dental plaques, favoring bacteria associated with a lower systemic inflammatory state. Assess the effect of DHA and ASA exposure on markers of systemic inflammation, including serum C-Reactive Protein (CRP), interleukin-6 (IL-6) and vascular adhesion molecule (VCAM) compared to ASA. Our hypothesis is that there will be a decrease in serum CRP, IL-6 and VCAM three months after exposure to DHA plus ASA compared to ASA alone. Assess the effect of DHA and ASA exposure on markers of systemic bone turnover, including urine N-terminal telopeptide (NTx) compared to ASA. Our hypothesis is that there will be a decrease in urine NTx three months after exposure to DHA plus ASA compared to ASA alone.

Official Title
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The Effects of Docosahexaenoic Acid on Periodontitis in Adults: A Pilot Randomized Controlled Trial

Conditions
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Periodontitis, Gingivitis, Inflammation

Intervention / Treatment
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* Drug: Aspirin
* Drug: Docosahexaenoic acid
* Drug: Placebo (for Docosahexaenoic acid)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >40 years >20 natural teeth (excluding third molars) no orthodontic appliances periodontitis defined as >4 teeth with pocket probing depths >5 mm Exclusion Criteria: pregnancy diabetes severe chronic diseases gastrointestinal bleeding uncontrolled chronic diseases autoimmune disorders conditions requiring antibiotic prophylaxis warfarin clopidogrel antimicrobial therapy within 30 days chronic use of non-steroidal anti-inflammatory drugs (other than aspirin) omega-3 fatty acid use within 6 months loose teeth painful teeth periodontal abscess pocket depths >10 mm in >1 tooth periodontal therapy within the past two years allergy to aspirin allergy to fish oil allergy to corn oil allergy to soybean oil

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aspirin & Docosahexaenoic acid<br>Aspirin 81 mg 1 tablet by mouth daily and Docosahexanoic acid (DHA) 500 mg 4 capsules by mouth daily (total daily dose of 2 grams DHA) for 3 months | Drug: Aspirin<br> <br> * Other names: Low Dose Aspirin;Drug: Docosahexaenoic acid<br> <br> * Other names: DHA;|
| Active Comparator: Aspirin & Placebo<br>Aspirin 81 mg by mouth daily and placebo (50% corn oil/50% soybean oil) 4 capsules by mouth daily for 3 months | Drug: Aspirin<br> <br> * Other names: Low Dose Aspirin;Drug: Placebo (for Docosahexaenoic acid)<br>* Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules<br>* Other names: 50% corn oil/50% soybean oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pocket Depth (mm) | Pocket probing depth (PD) is the depth a dental probe can be inserted into a gingival pocket at a particular site (6 sites per tooth) measured in millimeters among teeth with PD greater than or equal to 5 mm (N=533 dental sites total). | Baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gingival Index (0-3) | Gingival Index (GI) is a measure of gingival inflammation, which is assigned a score (0-3). Score Criteria: 0: No inflammation. Mild inflammation, slight change in color, slight edema, no bleeding on probing. Moderate inflammation, moderate glazing, redness, bleeding on probing. Severe inflammation, marked redness and hypertrophy, ulceration, tendency to spontaneous bleeding. | Baseline and 3 months | 
| Change in Plaque Index (0-3) | Plaque Index (PI) is a measure of gingival inflammation as induced by bacterial plaque deposition at and under the gum line. Score Criteria: 0: No plaque A film of plaque adhering to the free gingival margin and adjacent area of the tooth, which can not be seen with the naked eye. But only by using disclosing solution or by using probe. Moderate accumulation of deposits within the gingival pocket, on the gingival margin and/ or adjacent tooth surface, which can be seen with the naked eye. Abundance of soft matter within the gingival pocket and/or on the tooth and gingival margin. | Baseline and 3 months | 
| Sites With Bleeding on Probing (Yes/no) | Bleeding On Probing (BOP) is a measure of gingival inflammation and tissue destruction, which describes whether or not bleeding at the dental pocket occurred following probing. | 3 months | 
| Gingival Crevicular Fluid High Sensitivity C-reactive Protein | Gingival crevicular fluid (GCF) is the fluid bathing the teeth under the gum line. GCF samples were analyzed for high sensitivity C-reactive protein as a measure of local gingival inflammation. | Baseline and 3 months | 
| Gingival Crevicular Fluid Interleukin-6 | Gingival crevicular fluid (GCF) samples were analyzed for Interleukin-6, which is a measure of local gingival inflammation. | Baseline and 3 months | 
| Gingival Crevicular Fluid Interleukin-1 Beta | Gingival crevicular fluid (GCF) samples were analyzed for Interleukin-1 beta, which is a measure of local gingival inflammation. | Baseline and 3 months | 
| Serum High-sensitivity C-reactive Protein | Serum high-sensitivity C-reactive protein is a measure of systemic inflammation. | Baseline and 3 months | 
| Serum High-sensitivity Interleukin-6 | Serum high-sensitivity interleukin-6 is a measure of systemic inflammation. | Baseline and 3 months | 
| Serum Soluble Vascular Cell Adhesion Molecule | Serum soluble vascular cell adhesion molecule (VCAM) is a measure of systemic inflammation. | Baseline and 3 months | 
| Urine N-Terminal Telopeptides | Urine N-Terminal Telopeptides are a measure of systemic bone turnover. | Baseline and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Docosahexaenoic acid, DHA, Periodontitis, Gingivitis, Omega-3 fatty acid, Fish oil