The Effects of DHA on Periodontitis (DAP)

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

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

Study Overview

• Status: Completed
• Conditions: Inflammation; Periodontitis; Gingivitis
• Intervention / Treatment: Drug: Aspirin; Drug: Docosahexaenoic acid; Drug: Placebo (for Docosahexaenoic acid)

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.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin & 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	Drug: Aspirin; Other Names: Baby Aspirin; Low Dose Aspirin; Drug: Docosahexaenoic acid; Other Names: DHA
Active Comparator: Aspirin & Placebo; Aspirin 81 mg by mouth daily and placebo (50% corn oil/50% soybean oil) 4 capsules by mouth daily for 3 months	Drug: Aspirin; Other Names: Baby Aspirin; Low Dose Aspirin; Drug: Placebo (for Docosahexaenoic acid); Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules; Other Names: 50% corn oil/50% soybean oil

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Red Blood Cell Membrane Docosahexaenoic Acid	Red blood cell phospholipid fatty acids were measured at baseline and 3-month follow up as a measure of adherence.	Baseline and 3 months

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Harvard Medical School (HMS and HSDM); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Asghar Z Naqvi, MD, MPH, MNS, Beth Israel Deaconess Medical Center; Harvard Medical School; Study Chair: Kenneth J Mukamal, MD, MPH, MA, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Naqvi AZ, Mu L, Hasturk H, Van Dyke TE, Mukamal KJ, Goodson JM. Impact of Docosahexaenoic Acid Therapy on Subgingival Plaque Microbiota. J Periodontol. 2017 Sep;88(9):887-895. doi: 10.1902/jop.2017.160398. Epub 2017 May 18.
• Naqvi AZ, Hasturk H, Mu L, Phillips RS, Davis RB, Halem S, Campos H, Goodson JM, Van Dyke TE, Mukamal KJ. Docosahexaenoic Acid and Periodontitis in Adults: A Randomized Controlled Trial. J Dent Res. 2014 Aug;93(8):767-73. doi: 10.1177/0022034514541125. Epub 2014 Jun 26.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: October 30, 2013
• First Submitted That Met QC Criteria: October 30, 2013
• First Posted (Estimate): November 6, 2013

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Periodontitis; DHA; Fish oil; Docosahexaenoic acid; Omega-3 fatty acid; Gingivitis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Gingival Diseases; Periodontitis; Inflammation; Gingivitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: GM-023; UL1RR025758-02 (U.S. NIH Grant/Contract)