DAP: The Effects of DHA on Periodontitis

Sponsor
Beth Israel Deaconess Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT01976806
Collaborator
National Center for Research Resources (NCRR) (NIH), Harvard Medical School (HMS and HSDM) (Other)
55
1
2
27
2

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Aspirin
  • Drug: Docosahexaenoic acid
  • Drug: Placebo (for Docosahexaenoic acid)
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
55 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
The Effects of Docosahexaenoic Acid on Periodontitis in Adults: A Pilot Randomized Controlled Trial
Study Start Date :
Jun 1, 2009
Actual Primary Completion Date :
Sep 1, 2011
Actual Study Completion Date :
Sep 1, 2011

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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. 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.

    2. 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 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. Serum High-sensitivity C-reactive Protein [Baseline and 3 months]

      Serum high-sensitivity C-reactive protein is a measure of systemic inflammation.

    8. Serum High-sensitivity Interleukin-6 [Baseline and 3 months]

      Serum high-sensitivity interleukin-6 is a measure of systemic inflammation.

    9. Serum Soluble Vascular Cell Adhesion Molecule [Baseline and 3 months]

      Serum soluble vascular cell adhesion molecule (VCAM) is a measure of systemic inflammation.

    10. Urine N-Terminal Telopeptides [Baseline and 3 months]

      Urine N-Terminal Telopeptides are a measure of systemic bone turnover.

    Other Outcome Measures

    1. Change in Red Blood Cell Membrane Docosahexaenoic Acid [Baseline and 3 months]

      Red blood cell phospholipid fatty acids were measured at baseline and 3-month follow up as a measure of adherence.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215

    Sponsors and Collaborators

    • Beth Israel Deaconess Medical Center
    • National Center for Research Resources (NCRR)
    • Harvard Medical School (HMS and HSDM)

    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Kenneth Mukamal, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
    ClinicalTrials.gov Identifier:
    NCT01976806
    Other Study ID Numbers:
    • GM-023
    • UL1RR025758-02
    First Posted:
    Nov 6, 2013
    Last Update Posted:
    Dec 13, 2017
    Last Verified:
    Nov 1, 2017
    Keywords provided by Kenneth Mukamal, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

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

    Baseline Characteristics

    Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo Total
    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 Participants 24 22 46
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    53
    (8)
    57
    (8)
    55
    (8)
    Sex: Female, Male (Count of Participants)
    Female
    11
    45.8%
    10
    45.5%
    21
    45.7%
    Male
    13
    54.2%
    12
    54.5%
    25
    54.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    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%
    Black or African American
    7
    29.2%
    8
    36.4%
    15
    32.6%
    White
    12
    50%
    12
    54.5%
    24
    52.2%
    More than one race
    0
    0%
    1
    4.5%
    1
    2.2%
    Unknown or Not Reported
    1
    4.2%
    0
    0%
    1
    2.2%
    Smoking Status (participants) [Number]
    Current
    1
    4.2%
    1
    4.5%
    2
    4.3%
    Former
    7
    29.2%
    6
    27.3%
    13
    28.3%
    Never
    16
    66.7%
    15
    68.2%
    31
    67.4%
    BMI (kg/m2) (participants) [Number]
    Normal (18.5-24.9 kg/m2)
    9
    37.5%
    5
    22.7%
    14
    30.4%
    Overweight (25-30 kg/m2)
    4
    16.7%
    10
    45.5%
    14
    30.4%
    Obese (>30 kg/m2)
    11
    45.8%
    7
    31.8%
    18
    39.1%
    Hypertension (participants) [Number]
    Hypertension
    4
    16.7%
    6
    27.3%
    10
    21.7%
    No Hypertension
    20
    83.3%
    16
    72.7%
    36
    78.3%
    Hyperlipidemia (participants) [Number]
    Hyperlipidemia
    5
    20.8%
    4
    18.2%
    9
    19.6%
    No Hyperlipidemia
    19
    79.2%
    18
    81.8%
    37
    80.4%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
    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
    Measure Participants 24 22
    Mean (Standard Error) [mm]
    -0.71
    (0.07)
    -0.54
    (0.07)
    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
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    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
    Confidence Interval () %
    to
    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)
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
    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
    Measure Participants 24 22
    Mean (Standard Error) [GI units]
    -0.26
    (0.04)
    -0.07
    (0.04)
    3. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
    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
    Measure Participants 24 22
    Mean (Standard Error) [Plaque index units]
    -0.10
    (0.06)
    0.07
    (0.07)
    4. Secondary Outcome
    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

    Outcome Measure Data

    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
    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
    Measure Participants 24 22
    Measure Sites 271 261
    Count of Units [Sites]
    202
    227
    5. Secondary Outcome
    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

    Outcome Measure Data

    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
    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
    Measure Participants 20 19
    Mean (Standard Error) [ng/mL]
    -7.3715
    (3.9244)
    -3.1268
    (2.0415)
    6. Secondary Outcome
    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

    Outcome Measure Data

    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
    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
    Measure Participants 20 19
    Mean (Standard Error) [pg/mL]
    0.1422
    (0.5273)
    -0.00226
    (0.3245)
    7. Secondary Outcome
    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

    Outcome Measure Data

    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
    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
    Measure Participants 20 19
    Mean (Standard Error) [pg/mL]
    0.8775
    (4.7203)
    21.5816
    (8.0491)
    8. Secondary Outcome
    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

    Outcome Measure Data

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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
    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
    Measure Participants 20 21
    Mean (Standard Error) [pg/mL]
    0.3295
    (0.4149)
    -0.0690
    (0.2633)
    10. Secondary Outcome
    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

    Outcome Measure Data

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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
    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
    Measure Participants 21 19
    Mean (Standard Error) [nM BCE]
    103.3333
    (70.5656)
    61.8421
    (90.5793)
    12. Other Pre-specified Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aspirin & Docosahexaenoic Acid Aspirin & Placebo
    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
    Measure Participants 21 20
    Mean (Standard Error) [% of total RBC FA]
    2.723
    (0.3882)
    -0.1776
    (0.1326)

    Adverse Events

    Time Frame 3 months
    Adverse Event Reporting Description
    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)
    Arm/Group Description
    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 (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    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%) 0/28 (0%)
    Other (Not Including 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 7/27 (25.9%) 8/28 (28.6%)
    Blood and lymphatic system disorders
    Gingival bleeding while flossing 0/27 (0%) 0 1/28 (3.6%) 1
    Cardiac disorders
    Intermittent palpitations 1/27 (3.7%) 0/28 (0%)
    Gastrointestinal disorders
    Dyspepsia 2/27 (7.4%) 2 2/28 (7.1%) 2
    Flatulence 3/27 (11.1%) 3 1/28 (3.6%) 1
    Diarrhea 1/27 (3.7%) 1/28 (3.6%)
    Melena 0/27 (0%) 1/28 (3.6%)
    Nausea 0/27 (0%) 1/28 (3.6%)
    GERD 0/27 (0%) 1/28 (3.6%)
    General disorders
    Fatigue 2/27 (7.4%) 1/28 (3.6%)
    Headache 2/27 (7.4%) 0/28 (0%)
    Chipped tooth 1/27 (3.7%) 0/28 (0%)
    Diaphoresis 1/27 (3.7%) 0/28 (0%)
    Infections and infestations
    Upper respiratory infection 0/27 (0%) 1/28 (3.6%)
    Cavity 0/27 (0%) 1/28 (3.6%)
    Psychiatric disorders
    Verbally abusive toward staff 0/27 (0%) 1/28 (3.6%)

    Limitations/Caveats

    [Not Specified]

    More Information

    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
    Email kmukamal@bidmc.harvard.edu
    Responsible Party:
    Kenneth Mukamal, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
    ClinicalTrials.gov Identifier:
    NCT01976806
    Other Study ID Numbers:
    • GM-023
    • UL1RR025758-02
    First Posted:
    Nov 6, 2013
    Last Update Posted:
    Dec 13, 2017
    Last Verified:
    Nov 1, 2017