The Effects of DHA on Periodontitis

Phase 2

Completed

Conditions: Gingivitis
Inflammation
Periodontitis

Interventions: Drug: Aspirin
Drug: Docosahexaenoic acid
Drug: Placebo (for Docosahexaenoic acid)

Registration Number: NCT01976806

Lead Sponsor: Beth Israel Deaconess Medical Center

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

Detailed Description: 1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 55

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aspirin & Docosahexaenoic acid	Docosahexaenoic acid	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
Aspirin & Placebo	Placebo (for Docosahexaenoic acid)	Aspirin 81 mg by mouth daily and placebo (50% corn oil/50% soybean oil) 4 capsules by mouth daily for 3 months
Aspirin & Docosahexaenoic acid	Aspirin	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
Aspirin & Placebo	Aspirin	Aspirin 81 mg by mouth daily and placebo (50% corn oil/50% soybean oil) 4 capsules by mouth daily for 3 months

Primary Outcome Measures

Name	Time	Method
Change in Pocket Depth (mm)	Baseline and 3 months	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).

Secondary Outcome Measures

Name	Time	Method
Change in Gingival Index (0-3)	Baseline and 3 months	Gingival Index (GI) is a measure of gingival inflammation, which is assigned a score (0-3). Score Criteria: 0: No inflammation. 1. Mild inflammation, slight change in color, slight edema, no bleeding on probing. 2. Moderate inflammation, moderate glazing, redness, bleeding on probing. 3. Severe inflammation, marked redness and hypertrophy, ulceration, tendency to spontaneous bleeding.
Change in Plaque Index (0-3)	Baseline and 3 months	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 1. 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. 2. 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. 3. Abundance of soft matter within the gingival pocket and/or on the tooth and gingival margin.
Sites With Bleeding on Probing (Yes/no)	3 months	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.
Gingival Crevicular Fluid High Sensitivity C-reactive Protein	Baseline and 3 months	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.
Gingival Crevicular Fluid Interleukin-6	Baseline and 3 months	Gingival crevicular fluid (GCF) samples were analyzed for Interleukin-6, which is a measure of local gingival inflammation.
Gingival Crevicular Fluid Interleukin-1 Beta	Baseline and 3 months	Gingival crevicular fluid (GCF) samples were analyzed for Interleukin-1 beta, which is a measure of local gingival inflammation.
Serum High-sensitivity C-reactive Protein	Baseline and 3 months	Serum high-sensitivity C-reactive protein is a measure of systemic inflammation.
Serum High-sensitivity Interleukin-6	Baseline and 3 months	Serum high-sensitivity interleukin-6 is a measure of systemic inflammation.
Serum Soluble Vascular Cell Adhesion Molecule	Baseline and 3 months	Serum soluble vascular cell adhesion molecule (VCAM) is a measure of systemic inflammation.
Urine N-Terminal Telopeptides	Baseline and 3 months	Urine N-Terminal Telopeptides are a measure of systemic bone turnover.