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Dose-dependent Anti-inflammatory Effects of Vitamin D in a Human Gingivitis Model

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ClinicalTrials.gov Identifier: NCT00779909
Recruitment Status : Completed
First Posted : October 24, 2008
Results First Posted : October 2, 2017
Last Update Posted : October 2, 2017
Sponsor:
Collaborator:
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
Boston University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Gingivitis
Interventions Drug: vitamin D3
Other: Placebo
Enrollment 35
Recruitment Details  
Pre-assignment Details 102 potential participants were screened for study eligibility, 61 met various exclusions criteria, and 41 were found to be eligible for randomization. Of the 41 eligible subjects 35 were randomized into the trial. The 6 not randomized were either lost to follow-up or they lost interest and withdrew their consent for further involvement.
Arm/Group Title 1- Placebo 2- Vitamin D3, 500 IU 3- Vitamin D3 2500 IU 4- Vitamin D3 5000 IU
Hide Arm/Group Description placebo oral supplementation once per day for 12 weeks vitamin D3 500 IU oral supplementation once per day for 12 weeks vitamin D3 2500 IU oral supplementation once per day for 12 weeks vitamin D3 5000 IU oral supplementation once per day for 12 weeks
Period Title: Overall Study
Started 10 9 8 8
Completed 9 8 8 7
Not Completed 1 1 0 1
Reason Not Completed
Lost to Follow-up             1             0             0             1
Withdrawal by Subject             0             1             0             0
Arm/Group Title 1-Placebo 2-Vitamin D3, 500 IU 3-Vitamin D3, 2500 IU 4-Vitamin D3, 5000 IU Total
Hide Arm/Group Description placebo oral supplementation once per day for 12 weeks vitamin D3 500 IU oral supplementation once per day for 12 weeks vitamin D3 2500 IU oral supplementation once per day for 12 weeks vitamin D3 5000 IU oral supplementation once per day for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 10 9 8 8 35
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 8 participants 8 participants 35 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
 100.0%
9
 100.0%
8
 100.0%
8
 100.0%
35
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 8 participants 8 participants 35 participants
Female
5
  50.0%
6
  66.7%
7
  87.5%
5
  62.5%
23
  65.7%
Male
5
  50.0%
3
  33.3%
1
  12.5%
3
  37.5%
12
  34.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 8 participants 8 participants 35 participants
non-Hispanic Black
5
  50.0%
5
  55.6%
4
  50.0%
5
  62.5%
19
  54.3%
Non-Hispanic White
5
  50.0%
4
  44.4%
4
  50.0%
3
  37.5%
16
  45.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 10 participants 9 participants 8 participants 8 participants 35 participants
10
 100.0%
9
 100.0%
8
 100.0%
8
 100.0%
35
 100.0%
1.Primary Outcome
Title Proportion of Sites That Bleed on Probing
Hide Description Assessment of the bleeding index will be performed on oral and buccal sites. The periodontal probe will be moved gently across the marginal gingiva of all teeth of a quadrant. After 30 seconds, absence or presence of bleeding will be scored. The number of bleeding sites is used to calculate the gingival bleeding score.
Time Frame end of 4 week experimental gingivitis phase
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data for this outcome measure was not collected on any of the participants as it was overlooked and failure to collect these data did not come to the attention of the PI until after all follow-ups were completed.
Arm/Group Title 1- Placebo 2- Vitamin D3, 500 IU 3.Vitamin D3, 2500 IU 4- Vitamin D3 5000 IU
Hide Arm/Group Description:
placebo oral supplementation once per day for 12 weeks
vitamin D3: oral supplementation once per day for 12 weeks
vitamin D3: oral supplementation once per day for 12 weeks
vitamin D3: oral supplementation once per day for 12 weeks
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Mandibular Modified Gingival Index (MGI) Score
Hide Description The Modified Gingival Index (MGI) uses non-invasive/no probing and rates mild and moderate inflammation where: 0 = absence of inflammation; 1 = mild inflammation or with slight changes in color and texture but not in all portions of gingival marginal or papillary; 2 = mild inflammation, such as the preceding criteria, in all portions of gingival marginal or papillary; 3 = moderate, bright surface inflammation, erythema, edema and/or hypertrophy of gingival marginal or papillary; 4 = severe inflammation: erythema, edema and/or marginal gingival hypertrophy of the unit or spontaneous bleeding, papillary, congestion or ulceration. The MGI can be obtained by adding the values of each tooth and dividing by the number of teeth examined. The MGI may be scored for all surfaces of all or selected teeth or for selected areas of all or selected teeth. A score from 0.1-1.0 = mild inflammation; 1.1-2.0 = moderate inflammation from, and 2.1-3.0 signifies severe inflammation.
Time Frame week 8 and week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1- Placebo 2- Vitamin D3, 500 IU 3- Vitamin D3 2500 IU 4- Vitamin D3 5000 IU
Hide Arm/Group Description:
placebo oral supplementation once per day for 12 weeks
vitamin D3 500 IU oral supplementation once per day for 12 weeks
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
Overall Number of Participants Analyzed 9 8 8 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
8wk mandibular MGI score 1.83  (0.27) 1.76  (0.46) 1.62  (0.44) 1.67  (0.28)
12wk mandibular MGI score 2.12  (0.14) 1.97  (0.24) 2.02  (0.20) 2.19  (0.15)
3.Primary Outcome
Title Maxillary Modified Gingival Index (MGI) Score
Hide Description The Modified Gingival Index (MGI) uses non-invasive/no probing and rates mild and moderate inflammation where: 0 = absence of inflammation; 1 = mild inflammation or with slight changes in color and texture but not in all portions of gingival marginal or papillary; 2 = mild inflammation, such as the preceding criteria, in all portions of gingival marginal or papillary; 3 = moderate, bright surface inflammation, erythema, edema and/or hypertrophy of gingival marginal or papillary; 4 = severe inflammation: erythema, edema and/or marginal gingival hypertrophy of the unit or spontaneous bleeding, papillary, congestion or ulceration. The MGI can be obtained by adding the values of each tooth and dividing by the number of teeth examined. The MGI may be scored for all surfaces of all or selected teeth or for selected areas of all or selected teeth. A score from 0.1-1.0 = mild inflammation; 1.1-2.0 = moderate inflammation from, and 2.1-3.0 signifies severe inflammation.
Time Frame week 8 and week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1- Placebo 2- Vitamin D3, 500 IU 3- Vitamin D3 2500 IU 4- Vitamin D3 5000 IU
Hide Arm/Group Description:
placebo oral supplementation once per day for 12 weeks
vitamin D3 500 IU oral supplementation once per day for 12 weeks
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
Overall Number of Participants Analyzed 9 8 8 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
8wk maxillary MGI score 1.78  (0.29) 1.63  (0.40) 1.57  (0.39) 1.61  (0.31)
12wk maxillary MGI score 2.11  (0.16) 1.87  (0.30) 1.9  (0.30) 2.1  (0.10)
4.Secondary Outcome
Title Mandibular Plaque Index (PI) Score
Hide Description The Turesky plaque index was used. In this index, plaque is identified using a disclosing solution and scored using a 0 to 5 scale in which a score of 0= No plaque, 1= Separate flecks of plaque, 2= continuous band of plaque less or equal 1 mm, 3= Continuous band of plaque greater than 1 mm but less than 1/3 of crown height, 4= Continuous band of plaque greater or equal 1/3 but less or equal 2/3 of crown height, and 5= Continuous band of plaque greater 2/3 of crown height. Each tooth receives 6 individual scores at: mesial, middle, and distal scores for both the facial and lingual surfaces. An individual’s score is derived by adding the scores at each site and dividing by the number of sites evaluated. Higher scores denote higher plaque accumulation. Lower scores are more favorable.
Time Frame week 8 and week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1- Placebo 2- Vitamin D3, 500 IU 3- Vitamin D3 2500 IU 4- Vitamin D3 5000 IU
Hide Arm/Group Description:
placebo oral supplementation once per day for 12 weeks
vitamin D3 500 IU oral supplementation once per day for 12 weeks
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
Overall Number of Participants Analyzed 9 8 8 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
8wk mandibular PI score 1.84  (0.60) 1.77  (0.44) 1.82  (0.46) 1.82  (0.57)
12wk mandibular PI score 2.92  (0.71) 2.93  (0.50) 2.74  (0.52) 2.89  (0.32)
5.Secondary Outcome
Title Maxillary Plaque Index (PI) Score
Hide Description The Turesky plaque index was used. In this index, plaque is identified using a disclosing solution and scored using a 0 to 5 scale in which a score of 0= No plaque, 1= Separate flecks of plaque, 2= continuous band of plaque less or equal 1 mm, 3= Continuous band of plaque greater than 1 mm but less than 1/3 of crown height, 4= Continuous band of plaque greater or equal 1/3 but less or equal 2/3 of crown height, and 5= Continuous band of plaque greater 2/3 of crown height. Each tooth receives 6 individual scores at: mesial, middle, and distal scores for both the facial and lingual surfaces. An individual’s score is derived by adding the scores at each site and dividing by the number of sites evaluated. Higher scores denote higher plaque accumulation. Lower scores are more favorable.
Time Frame week 8 and week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1- Placebo 2- Vitamin D3, 500 IU 3- Vitamin D3 2500 IU 4- Vitamin D3 5000 IU
Hide Arm/Group Description:
placebo oral supplementation once per day for 12 weeks
vitamin D3 500 IU oral supplementation once per day for 12 weeks
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
Overall Number of Participants Analyzed 9 8 8 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
8wk maxillary PI score 1.56  (0.55) 1.71  (0.44) 1.69  (0.49) 1.68  (0.56)
12 wk maxillary PI score 2.77  (0.42) 3  (0.32) 2.81  (0.32) 2.89  (0.47)
6.Secondary Outcome
Title Gingival Crevicular Fluid (GCF) Volume
Hide Description GCF will be collected by placing a filter paper strip at the opening of the gingival crevice. After carefully removing the supragingival plaque from the sampling area, a paper strip will be placed for 30s or until visibly wet. Sampling time will be recorded and GCF volume collected with each sample will be quantified using a Periotron device. GCF volume will be sampled from three mesial sites per subject: The upper left central incisor, the first upper left premolar and the first upper left molar. Should any of these teeth be missing, substitution will occur in the following order (i) the contralateral tooth, (ii) the distally adjacent tooth, or (iii) the distally adjacent tooth of the contralateral tooth. Should a sample be visibly contaminated with blood, the sample will be discarded and substitution will occur as described above.
Time Frame week 8 and week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-Placebo 2-Vitamin D3, 500 IU 3-Vitamin D3, 2500 IU 4-Vitamin D3, 5000 IU
Hide Arm/Group Description:
placebo oral supplementation once per day for 12 weeks
vitamin D3 500 IU oral supplementation once per day for 12 weeks
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
Overall Number of Participants Analyzed 9 8 8 7
Mean (Standard Deviation)
Unit of Measure: ul
8wk GCF volume site 1 38.1  (12.5) 49.1  (21.3) 37.1  (10.0) 57.6  (24.2)
12wk GCF volume site 1 50.8  (13.1) 66.5  (31.8) 35.1  (7.8) 55.9  (48.0)
8wk GCF volume site 2 53.7  (9.8) 53.5  (23.4) 42.5  (27.4) 61.0  (36.0)
12wk GCF volume site 2 83.6  (24.5) 71.9  (29.5) 54.3  (24.6) 72.4  (39.6)
8wk GCF volume site 3 70.4  (32.9) 92.9  (26.0) 58.4  (19.7) 59.9  (16.5)
12wk GCF volume site 3 95.9  (27.4) 99.1  (37.7) 64.8  (20.0) 92  (39.7)
7.Secondary Outcome
Title Gingival Crevicular Fluid (GCF) Concentrations of TNF-alpha, IL1-beta, IL-2, IL-12
Hide Description

GCF will be collected by placing a filter paper strip at the opening of the gingival crevice. After carefully removing the supragingival plaque from the sampling area, a paper strip will be placed for 30s or until visibly wet. Sampling time will be recorded and GCF volume collected with each sample will be quantified using a Periotron device.

GCF volume will be sampled from three mesial sites per subject: The upper left central incisor, the first upper left premolar and the first upper left molar. Should any of these teeth be missing, substitution will occur in the following order (i) the contralateral tooth, (ii) the distally adjacent tooth, or (iii) the distally adjacent tooth of the contralateral tooth. Should a sample be visibly contaminated with blood, the sample will be discarded and substitution will occur as described above. Concentrations of TNF-alpha, IL-1 beta, IL-2, and IL-12 will be measured and means and SDs will be calculated for each study arm.

Time Frame week 8 and week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-Placebo 2-Vitamin D3, 500 IU 3-Vitamin D3, 2500 IU 4-Vitamin D3, 5000 IU
Hide Arm/Group Description:
placebo oral supplementation once per day for 12 weeks
vitamin D3 500 IU oral supplementation once per day for 12 weeks
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
Overall Number of Participants Analyzed 9 8 8 7
Mean (Standard Deviation)
Unit of Measure: pg/site
8wk TNF-alpha 0.97  (1.14) 1.53  (1.86) 1.34  (1.93) 1.87  (3.14)
12wk TNF-alpha 1.00  (1.04) 1.11  (1.32) 1.73  (3.02) 7.94  (18.12)
8wk IL-1 beta 0.04  (0.00) 0.05  (0.02) 0.04  (0.00) 0.04  (0.00)
12wk IL-1 beta 0.04  (0.00) 0.04  (0.02) 0.04  (0.00) 0.04  (0.00)
8wk IL-2 24.11  (34.83) 13.44  (2.66) 13.13  (6.52) 13.07  (6.71)
12wk IL-2 20.78  (17.31) 12.5  (0.00) 12.56  (0.18) 13.36  (1.70)
8wk IL-12 0.65  (1.22) 0.11  (0.17) 0.03  (0.04) 0.96  (2.10)
12wk IL-12 0.62  (1.10) 0.06  (0.07) 0.02  (0.01) 1.08  (2.28)
8.Secondary Outcome
Title Serum Calcium
Hide Description The serum calcium blood test measures the total calcium in the participants' blood. The normal range for total serum calcium concentration in adults is 8.9-10.2 mg/dL.
Time Frame week 7, week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-Placebo 2-Vitamin D3, 500 IU 3-Vitamin D3, 2500 IU 4-Vitamin D3, 5000 IU
Hide Arm/Group Description:
placebo oral supplementation once per day for 12 weeks
vitamin D3 500 IU oral supplementation once per day for 12 weeks
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
Overall Number of Participants Analyzed 9 8 8 7
Mean (Standard Deviation)
Unit of Measure: mg/dl
7wk serum calcium 9.6  (0.4) 9.1  (0.3) 9.2  (0.3) 9.1  (0.5)
12wk serum calcium 9.4  (0.4) 9.2  (0.5) 9.2  (0.3) 9.3  (0.2)
9.Secondary Outcome
Title Urinary Calcium/Creatinine Ratio
Hide Description Urinary calcium ratios were calculated from urine samples at week 4, 7, and 12. A normal reference interval for the urine calcium (mg/dL):urine creatinine (mg/dL) ratio is <0.14.
Time Frame week 4, week 7, week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-Placebo 2-Vitamin D3, 500 IU 3-Vitamin D3, 2500 IU 4-Vitamin D3, 5000 IU
Hide Arm/Group Description:
placebo oral supplementation once per day for 12 weeks
vitamin D3 500 IU oral supplementation once per day for 12 weeks
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
Overall Number of Participants Analyzed 9 8 8 7
Mean (Standard Deviation)
Unit of Measure: ratio
4wk calcium/creatinine ratio 0.07  (0.1) 0.06  (0.03) 0.07  (0.04) 0.09  (0.01)
7wk calcium/creatinine ratio 0.09  (0.1) 0.07  (0.04) 0.09  (0.02) 0.13  (0.13)
12wk calcium/creatinine ratio 0.12  (0.1) 0.07  (0.03) 0.11  (0.09) 0.11  (0.07)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 1- Placebo 2- Vitamin D3, 500 IU 3- Vitamin D3 2500 IU 4- Vitamin D3 5000 IU
Hide Arm/Group Description placebo oral supplementation once per day for 12 weeks vitamin D3, 500 IU capsule once per day for 12 weeks vitamin D3, 2500 IU capsule once per day for 12 weeks vitamin D3, 5000 IU capsule once per day for 12 weeks
All-Cause Mortality
1- Placebo 2- Vitamin D3, 500 IU 3- Vitamin D3 2500 IU 4- Vitamin D3 5000 IU
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/8 (0.00%)   0/8 (0.00%)   0/7 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
1- Placebo 2- Vitamin D3, 500 IU 3- Vitamin D3 2500 IU 4- Vitamin D3 5000 IU
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/8 (0.00%)   0/8 (0.00%)   0/7 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
1- Placebo 2- Vitamin D3, 500 IU 3- Vitamin D3 2500 IU 4- Vitamin D3 5000 IU
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/8 (0.00%)   1/8 (12.50%)   0/7 (0.00%) 
Musculoskeletal and connective tissue disorders         
Joint pain   0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/7 (0.00%) 
Indicates events were collected by systematic assessment
There were recruitment delays due to the potential seasonal impact on vitamin D levels from the sun and the research center was relocated. Both resulted in lower enrollment during the funded time frame than originally projected.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Raul I Garcia, DMD
Organization: Boston University School of Dental Medicine
Phone: 617-638-6385
EMail: rig@bu.edu
Responsible Party: Boston University
ClinicalTrials.gov Identifier: NCT00779909     History of Changes
Other Study ID Numbers: H-26461
R21AT003714-01 ( U.S. NIH Grant/Contract )
First Submitted: October 22, 2008
First Posted: October 24, 2008
Results First Submitted: May 26, 2017
Results First Posted: October 2, 2017
Last Update Posted: October 2, 2017