The Effects of DHA on Periodontitis (DAP)
Primary Purpose
Periodontitis, Gingivitis, Inflammation
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aspirin
Docosahexaenoic acid
Placebo (for Docosahexaenoic acid)
Sponsored by
About this trial
This is an interventional treatment trial for Periodontitis focused on measuring Docosahexaenoic acid, DHA, Periodontitis, Gingivitis, Omega-3 fatty acid, Fish oil
Eligibility Criteria
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
Sites / Locations
- Beth Israel Deaconess Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Aspirin & Docosahexaenoic acid
Aspirin & Placebo
Arm Description
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 81 mg by mouth daily and placebo (50% corn oil/50% soybean oil) 4 capsules by mouth daily for 3 months
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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.
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.
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.
Gingival Crevicular Fluid Interleukin-6
Gingival crevicular fluid (GCF) samples were analyzed for Interleukin-6, which is a measure of local gingival inflammation.
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.
Serum High-sensitivity C-reactive Protein
Serum high-sensitivity C-reactive protein is a measure of systemic inflammation.
Serum High-sensitivity Interleukin-6
Serum high-sensitivity interleukin-6 is a measure of systemic inflammation.
Serum Soluble Vascular Cell Adhesion Molecule
Serum soluble vascular cell adhesion molecule (VCAM) is a measure of systemic inflammation.
Urine N-Terminal Telopeptides
Urine N-Terminal Telopeptides are a measure of systemic bone turnover.
Full Information
NCT ID
NCT01976806
First Posted
October 30, 2013
Last Updated
November 17, 2017
Sponsor
Beth Israel Deaconess Medical Center
Collaborators
National Center for Research Resources (NCRR), Harvard Medical School (HMS and HSDM)
1. Study Identification
Unique Protocol Identification Number
NCT01976806
Brief Title
The Effects of DHA on Periodontitis
Acronym
DAP
Official Title
The Effects of Docosahexaenoic Acid on Periodontitis in Adults: A Pilot Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center
Collaborators
National Center for Research Resources (NCRR), Harvard Medical School (HMS and HSDM)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Periodontitis, Gingivitis, Inflammation
Keywords
Docosahexaenoic acid, DHA, Periodontitis, Gingivitis, Omega-3 fatty acid, Fish oil
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
55 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aspirin & Docosahexaenoic acid
Arm Type
Experimental
Arm Description
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
Arm Title
Aspirin & Placebo
Arm Type
Active Comparator
Arm Description
Aspirin 81 mg by mouth daily and placebo (50% corn oil/50% soybean oil) 4 capsules by mouth daily for 3 months
Intervention Type
Drug
Intervention Name(s)
Aspirin
Other Intervention Name(s)
Baby Aspirin, Low Dose Aspirin
Intervention Type
Drug
Intervention Name(s)
Docosahexaenoic acid
Other Intervention Name(s)
DHA
Intervention Type
Drug
Intervention Name(s)
Placebo (for Docosahexaenoic acid)
Other Intervention Name(s)
50% corn oil/50% soybean oil
Intervention Description
Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules
Primary Outcome Measure Information:
Title
Change in Pocket Depth (mm)
Description
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).
Time Frame
Baseline and 3 months
Secondary Outcome Measure Information:
Title
Change in Gingival Index (0-3)
Description
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.
Time Frame
Baseline and 3 months
Title
Change in Plaque Index (0-3)
Description
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.
Time Frame
Baseline and 3 months
Title
Sites With Bleeding on Probing (Yes/no)
Description
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.
Time Frame
3 months
Title
Gingival Crevicular Fluid High Sensitivity C-reactive Protein
Description
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.
Time Frame
Baseline and 3 months
Title
Gingival Crevicular Fluid Interleukin-6
Description
Gingival crevicular fluid (GCF) samples were analyzed for Interleukin-6, which is a measure of local gingival inflammation.
Time Frame
Baseline and 3 months
Title
Gingival Crevicular Fluid Interleukin-1 Beta
Description
Gingival crevicular fluid (GCF) samples were analyzed for Interleukin-1 beta, which is a measure of local gingival inflammation.
Time Frame
Baseline and 3 months
Title
Serum High-sensitivity C-reactive Protein
Description
Serum high-sensitivity C-reactive protein is a measure of systemic inflammation.
Time Frame
Baseline and 3 months
Title
Serum High-sensitivity Interleukin-6
Description
Serum high-sensitivity interleukin-6 is a measure of systemic inflammation.
Time Frame
Baseline and 3 months
Title
Serum Soluble Vascular Cell Adhesion Molecule
Description
Serum soluble vascular cell adhesion molecule (VCAM) is a measure of systemic inflammation.
Time Frame
Baseline and 3 months
Title
Urine N-Terminal Telopeptides
Description
Urine N-Terminal Telopeptides are a measure of systemic bone turnover.
Time Frame
Baseline and 3 months
Other Pre-specified Outcome Measures:
Title
Change in Red Blood Cell Membrane Docosahexaenoic Acid
Description
Red blood cell phospholipid fatty acids were measured at baseline and 3-month follow up as a measure of adherence.
Time Frame
Baseline and 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Asghar Z Naqvi, MD, MPH, MNS
Organizational Affiliation
Beth Israel Deaconess Medical Center; Harvard Medical School
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kenneth J Mukamal, MD, MPH, MA
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28517974
Citation
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.
Results Reference
background
PubMed Identifier
24970858
Citation
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.
Results Reference
result
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The Effects of DHA on Periodontitis
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