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The Effects of DHA on Periodontitis (DAP)

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ClinicalTrials.gov Identifier: NCT01976806
Recruitment Status : Completed
First Posted : November 6, 2013
Results First Posted : March 24, 2014
Last Update Posted : December 13, 2017
Sponsor:
Collaborators:
National Center for Research Resources (NCRR)
Harvard Medical School
Information provided by (Responsible Party):
Kenneth Mukamal, Beth Israel Deaconess Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Periodontitis
Gingivitis
Inflammation
Interventions Drug: Aspirin
Drug: Docosahexaenoic acid
Drug: Placebo (for Docosahexaenoic acid)
Enrollment 55

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Period Title: Overall Study
Started 27 28
Completed 24 22
Not Completed 3 6
Reason Not Completed
Lost to Follow-up             1             4
Adverse Event             1             1
Withdrawal by Subject             1             1
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo Total
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Total of all reporting groups
Overall Number of Baseline Participants 24 22 46
Hide Baseline Analysis Population Description
Includes all subjects that completed follow-up
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 22 participants 46 participants
53  (8) 57  (8) 55  (8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Female
11
  45.8%
10
  45.5%
21
  45.7%
Male
13
  54.2%
12
  54.5%
25
  54.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
4
  16.7%
1
   4.5%
5
  10.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
  29.2%
8
  36.4%
15
  32.6%
White
12
  50.0%
12
  54.5%
24
  52.2%
More than one race
0
   0.0%
1
   4.5%
1
   2.2%
Unknown or Not Reported
1
   4.2%
0
   0.0%
1
   2.2%
Smoking Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Current 1 1 2
Former 7 6 13
Never 16 15 31
BMI (kg/m2)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Normal (18.5-24.9 kg/m2) 9 5 14
Overweight (25-30 kg/m2) 4 10 14
Obese (>30 kg/m2) 11 7 18
Hypertension  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Hypertension 4 6 10
No Hypertension 20 16 36
Hyperlipidemia  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Hyperlipidemia 5 4 9
No Hyperlipidemia 19 18 37
1.Primary Outcome
Title Change in Pocket Depth (mm)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 24 22
Mean (Standard Error)
Unit of Measure: mm
-0.71  (0.07) -0.54  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aspirin & Docosahexaenoic Acid, Aspirin & Placebo
Comments Intent-to-treat basis with a type I error rate of 0.05. The follow-up pocket depth, was assessed in linear mixed effects models with a compound-symmetry covariance structure and age, sex, BMI, race, baseline pocket depth, baseline red blood cell (RBC) DHA level (dichotomized at median), and intervention group as fixed-effect variables.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Mixed Models Analysis
Comments Compound-symmetry covariance structure with age, sex, BMI, race, baseline pocket depth, baseline RBC DHA level, and intervention group variables
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments Mean change in pocket depth (3-month follow-up minus baseline) among dental sites with baseline pocket depths >=5 mm in the DHA intervention group versus the placebo group.
2.Secondary Outcome
Title Change in Gingival Index (0-3)
Hide Description

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.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 24 22
Mean (Standard Error)
Unit of Measure: GI units
-0.26  (0.04) -0.07  (0.04)
3.Secondary Outcome
Title Change in Plaque Index (0-3)
Hide 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

  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.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 24 22
Mean (Standard Error)
Unit of Measure: Plaque index units
-0.10  (0.06) 0.07  (0.07)
4.Secondary Outcome
Title Sites With Bleeding on Probing (Yes/no)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Results presented at 3 months; 3-months results also compared to baseline BOP using logistic regression as described in manuscript.
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 24 22
Overall Number of Units Analyzed
Type of Units Analyzed: Sites
271 261
Count of Units
Unit of Measure: Sites
202
  74.5%
227
  87.0%
5.Secondary Outcome
Title Gingival Crevicular Fluid High Sensitivity C-reactive Protein
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Performed in all participants with baseline and 3 month visits in whom usable GCF samples could be collected.
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 20 19
Mean (Standard Error)
Unit of Measure: ng/mL
-7.3715  (3.9244) -3.1268  (2.0415)
6.Secondary Outcome
Title Gingival Crevicular Fluid Interleukin-6
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Performed in all participants with baseline and 3 month visits in whom usable GCF samples could be collected.
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 20 19
Mean (Standard Error)
Unit of Measure: pg/mL
0.1422  (0.5273) -0.00226  (0.3245)
7.Secondary Outcome
Title Gingival Crevicular Fluid Interleukin-1 Beta
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Performed in all participants with baseline and 3 month visits in whom usable GCF samples could be collected.
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 20 19
Mean (Standard Error)
Unit of Measure: pg/mL
0.8775  (4.7203) 21.5816  (8.0491)
8.Secondary Outcome
Title Serum High-sensitivity C-reactive Protein
Hide Description Serum high-sensitivity C-reactive protein is a measure of systemic inflammation.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 24 22
Mean (Standard Error)
Unit of Measure: mg/L
-0.3695  (0.5558) 0.7114  (0.7223)
9.Secondary Outcome
Title Serum High-sensitivity Interleukin-6
Hide Description Serum high-sensitivity interleukin-6 is a measure of systemic inflammation.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 20 21
Mean (Standard Error)
Unit of Measure: pg/mL
0.3295  (0.4149) -0.0690  (0.2633)
10.Secondary Outcome
Title Serum Soluble Vascular Cell Adhesion Molecule
Hide Description Serum soluble vascular cell adhesion molecule (VCAM) is a measure of systemic inflammation.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 20 21
Mean (Standard Error)
Unit of Measure: ng/mL
4.8829  (24.3667) 27.9409  (19.6992)
11.Secondary Outcome
Title Urine N-Terminal Telopeptides
Hide Description Urine N-Terminal Telopeptides are a measure of systemic bone turnover.
Time Frame Baseline and 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 21 19
Mean (Standard Error)
Unit of Measure: nM BCE
103.3333  (70.5656) 61.8421  (90.5793)
12.Other Pre-specified Outcome
Title Change in Red Blood Cell Membrane Docosahexaenoic Acid
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
Hide Arm/Group 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

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

Placebo (for Docosahexaenoic acid): Placebo (corn/soybean oil) capsules manufactured to look identical to DHA capsules

Overall Number of Participants Analyzed 21 20
Mean (Standard Error)
Unit of Measure: % of total RBC FA
2.723  (0.3882) -0.1776  (0.1326)
Time Frame 3 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DHA 2 gm (4 Caps) + Aspirin 81 mg (1 Tablet by Mouth Per Day) Placebo (4 Caps) + Aspirin 81 mg (1 Tablet by Mouth Per Day)
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
DHA 2 gm (4 Caps) + Aspirin 81 mg (1 Tablet by Mouth Per Day) Placebo (4 Caps) + Aspirin 81 mg (1 Tablet by Mouth Per Day)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
DHA 2 gm (4 Caps) + Aspirin 81 mg (1 Tablet by Mouth Per Day) Placebo (4 Caps) + Aspirin 81 mg (1 Tablet by Mouth Per Day)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/27 (0.00%)      0/28 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
DHA 2 gm (4 Caps) + Aspirin 81 mg (1 Tablet by Mouth Per Day) Placebo (4 Caps) + Aspirin 81 mg (1 Tablet by Mouth Per Day)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/27 (25.93%)      8/28 (28.57%)    
Blood and lymphatic system disorders     
Gingival bleeding while flossing   0/27 (0.00%)  0 1/28 (3.57%)  1
Cardiac disorders     
Intermittent palpitations   1/27 (3.70%)  0/28 (0.00%) 
Gastrointestinal disorders     
Dyspepsia   2/27 (7.41%)  2 2/28 (7.14%)  2
Flatulence   3/27 (11.11%)  3 1/28 (3.57%)  1
Diarrhea   1/27 (3.70%)  1/28 (3.57%) 
Melena   0/27 (0.00%)  1/28 (3.57%) 
Nausea   0/27 (0.00%)  1/28 (3.57%) 
GERD   0/27 (0.00%)  1/28 (3.57%) 
General disorders     
Fatigue   2/27 (7.41%)  1/28 (3.57%) 
Headache   2/27 (7.41%)  0/28 (0.00%) 
Chipped tooth   1/27 (3.70%)  0/28 (0.00%) 
Diaphoresis   1/27 (3.70%)  0/28 (0.00%) 
Infections and infestations     
Upper respiratory infection   0/27 (0.00%)  1/28 (3.57%) 
Cavity   0/27 (0.00%)  1/28 (3.57%) 
Psychiatric disorders     
Verbally abusive toward staff   0/27 (0.00%)  1/28 (3.57%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Kenneth Mukamal
Organization: Beth Israel Deaconess Medical Center
Phone: 617-754-1401
Responsible Party: Kenneth Mukamal, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01976806     History of Changes
Other Study ID Numbers: GM-023
UL1RR025758-02 ( U.S. NIH Grant/Contract )
First Submitted: October 30, 2013
First Posted: November 6, 2013
Results First Submitted: December 3, 2013
Results First Posted: March 24, 2014
Last Update Posted: December 13, 2017