Dose-dependent Anti-inflammatory Effects of Vitamin D in a Human Gingivitis Model
| Status: | Completed |
|---|---|
| Conditions: | Dental |
| Therapuetic Areas: | Dental / Maxillofacial Surgery |
| Healthy: | No |
| Age Range: | 18 - 64 |
| Updated: | 10/4/2017 |
| Start Date: | December 2008 |
| End Date: | September 2011 |
The burden of chronic gingivitis and periodontitis in the US is disproportionately high among
Non-Hispanic Blacks compared to Non-Hispanic Whites. Chronic gingivitis is a highly prevalent
chronic inflammatory disease that may progress into periodontitis, a major cause of tooth
loss, Data from in-vitro and animal studies suggest anti-inflammatory effects of vitamin D;
however, if and over what dose-range vitamin D may have anti-inflammatory effects in humans
is uncertain. Recent clinical studies indicate that beneficial effects of vitamin D for
several important outcomes may occur over a wide range of serum 25-hydroxyvitamin D (25-OHD)
concentrations, possibly up to concentrations that would require vitamin D intakes ranging
from 2 to more than 10 ten times higher than the current RDA for vitamin D. Because dark skin
pigmentation is a potent inhibitor of vitamin D photosynthesis, Non-Hispanic Blacks have much
lower 25-OHD serum levels than Non-Hispanic Whites. These differences in vitamin D status may
partially explain the racial disparities in prevalence of chronic gingivitis and
periodontitis observed in the US.
We hypothesize that oral cholecalciferol supplementation can reduce susceptibility to
gingivitis over a wide range of serum 25-OHD concentrations in Non-Hispanic Whites and
Non-Hispanic Blacks. We propose to conduct a simple, single-center, randomized, double-blind,
placebo-controlled parallel-group dose-ranging study. We will compare placebo to doses of 500
IU, 2,500 IU and 5,000 IU vitamin D3 per day. We will compare the severity of gingival
inflammation that develops in response to a 28-day period of unlimited plaque growth
(experimental gingivitis) between dosage groups. Furthermore, we will evaluate the
association between achieved 25-OHD levels and gingival inflammation.
The results of this study will have several important implications, as dietary vitamin D
supplementation may be a simple, safe and inexpensive means by which to reduce racial/ethnic
disparities in gingivitis, as well as to reduce the overall burden of oral disease in the
population as a whole. The study will elucidate the dose-response relationship of the
anti-inflammatory effects of vitamin D, which in turn may lead to a revision of the current
recommendations regarding nutritional supplementation of vitamin D in order to optimize the
prevention of important medical conditions and diseases and reduce racial health disparities.
Non-Hispanic Blacks compared to Non-Hispanic Whites. Chronic gingivitis is a highly prevalent
chronic inflammatory disease that may progress into periodontitis, a major cause of tooth
loss, Data from in-vitro and animal studies suggest anti-inflammatory effects of vitamin D;
however, if and over what dose-range vitamin D may have anti-inflammatory effects in humans
is uncertain. Recent clinical studies indicate that beneficial effects of vitamin D for
several important outcomes may occur over a wide range of serum 25-hydroxyvitamin D (25-OHD)
concentrations, possibly up to concentrations that would require vitamin D intakes ranging
from 2 to more than 10 ten times higher than the current RDA for vitamin D. Because dark skin
pigmentation is a potent inhibitor of vitamin D photosynthesis, Non-Hispanic Blacks have much
lower 25-OHD serum levels than Non-Hispanic Whites. These differences in vitamin D status may
partially explain the racial disparities in prevalence of chronic gingivitis and
periodontitis observed in the US.
We hypothesize that oral cholecalciferol supplementation can reduce susceptibility to
gingivitis over a wide range of serum 25-OHD concentrations in Non-Hispanic Whites and
Non-Hispanic Blacks. We propose to conduct a simple, single-center, randomized, double-blind,
placebo-controlled parallel-group dose-ranging study. We will compare placebo to doses of 500
IU, 2,500 IU and 5,000 IU vitamin D3 per day. We will compare the severity of gingival
inflammation that develops in response to a 28-day period of unlimited plaque growth
(experimental gingivitis) between dosage groups. Furthermore, we will evaluate the
association between achieved 25-OHD levels and gingival inflammation.
The results of this study will have several important implications, as dietary vitamin D
supplementation may be a simple, safe and inexpensive means by which to reduce racial/ethnic
disparities in gingivitis, as well as to reduce the overall burden of oral disease in the
population as a whole. The study will elucidate the dose-response relationship of the
anti-inflammatory effects of vitamin D, which in turn may lead to a revision of the current
recommendations regarding nutritional supplementation of vitamin D in order to optimize the
prevention of important medical conditions and diseases and reduce racial health disparities.
Vitamin D is important for healthy bones. More recently, anti-inflammatory effects of vitamin
D have been found in laboratory and animal studies and vitamin D may be beneficial for
inflammatory diseases. Gingivitis is a common inflammatory disease of the gums that develops
in response to bacterial components in dental plaque. The degree to which gingivitis develops
in response to a given amount of plaque may vary between different individuals. With this
study, we want to investigate whether oral supplementation with vitamin D can reduce the
susceptibility to gingivitis in non-Hispanic Whites and African Americans.
We plan to randomize 120 healthy volunteers (60 Non-Hispanic Whites, 60 Non-Hispanic Blacks)
during the wintertime who will abstain from oral hygiene measures (brushing, flossing or
antiseptic mouth rinses) for a period of 4 weeks to allow accumulation of plaque and
development of gingivitis. These subjects will be randomly allocated to receive either oral
supplementation with placebo, 500 IU, 2500 IU or 5000 IU vitamin D3 per day starting 8 weeks
prior to the experimental gingivitis period for a total of 12 weeks. The development of
gingivitis will be measured using clinical indices of gingival inflammation, inflammatory
biomarker in gingival crevicular fluid (GCF) and GCF volume. Before and after completion of
the experimental gingivitis phase, all subjects will receive a professional cleaning of their
teeth to ensure complete resolution of inflammation.Blood samples will be collected at the
screening examination, baseline, week 7, and after week 12 (end of trial) to determine serum
levels of 25-hydroxyvitamin D, parathyroid hormone , serum calcium and to archive serum and
plasma samples. In addition urine samples will be collected at baseline and weeks 4,7 and 12
to determine calcium excretion and to archive urine samples for future analyses. Mandibular
and maxillary Modified Gingival Index (MGI) Scores, Plaque Index (PI) scores, and GCF
sampling to measure volume and assess for biomarkers (TNF-LPH, IL-1 beta, IL-2, IL-12) will
be done at 8 and 12 weeks.
Following recruitment and consent those subjects deemed eligible for further screening will
then be referred to the BUMC GCRC in order to have two components of the screening procedure
performed:Electrocardiogram and a blood draw to be sent to Quest for analysis of Vit D and
PTH levels.
The extent to which gingivitis develops during the 4-week period of plaque accumulation will
be compared between the two experimental groups. Furthermore, we will evaluate the
association between serum levels of 25-OHD and the development of gingivitis as well as serum
markers of inflammation.
D have been found in laboratory and animal studies and vitamin D may be beneficial for
inflammatory diseases. Gingivitis is a common inflammatory disease of the gums that develops
in response to bacterial components in dental plaque. The degree to which gingivitis develops
in response to a given amount of plaque may vary between different individuals. With this
study, we want to investigate whether oral supplementation with vitamin D can reduce the
susceptibility to gingivitis in non-Hispanic Whites and African Americans.
We plan to randomize 120 healthy volunteers (60 Non-Hispanic Whites, 60 Non-Hispanic Blacks)
during the wintertime who will abstain from oral hygiene measures (brushing, flossing or
antiseptic mouth rinses) for a period of 4 weeks to allow accumulation of plaque and
development of gingivitis. These subjects will be randomly allocated to receive either oral
supplementation with placebo, 500 IU, 2500 IU or 5000 IU vitamin D3 per day starting 8 weeks
prior to the experimental gingivitis period for a total of 12 weeks. The development of
gingivitis will be measured using clinical indices of gingival inflammation, inflammatory
biomarker in gingival crevicular fluid (GCF) and GCF volume. Before and after completion of
the experimental gingivitis phase, all subjects will receive a professional cleaning of their
teeth to ensure complete resolution of inflammation.Blood samples will be collected at the
screening examination, baseline, week 7, and after week 12 (end of trial) to determine serum
levels of 25-hydroxyvitamin D, parathyroid hormone , serum calcium and to archive serum and
plasma samples. In addition urine samples will be collected at baseline and weeks 4,7 and 12
to determine calcium excretion and to archive urine samples for future analyses. Mandibular
and maxillary Modified Gingival Index (MGI) Scores, Plaque Index (PI) scores, and GCF
sampling to measure volume and assess for biomarkers (TNF-LPH, IL-1 beta, IL-2, IL-12) will
be done at 8 and 12 weeks.
Following recruitment and consent those subjects deemed eligible for further screening will
then be referred to the BUMC GCRC in order to have two components of the screening procedure
performed:Electrocardiogram and a blood draw to be sent to Quest for analysis of Vit D and
PTH levels.
The extent to which gingivitis develops during the 4-week period of plaque accumulation will
be compared between the two experimental groups. Furthermore, we will evaluate the
association between serum levels of 25-OHD and the development of gingivitis as well as serum
markers of inflammation.
Inclusion Criteria:
- informed written consent
- healthy subjects age 18-64 years old
- serum 25-hydroxyvitamin D concentration <62.5 nmol/L (<25 ng/mL)
Exclusion Criteria:
- increased risk for infectious endocarditis that require antibiotic prophylaxis prior
to periodontal probing
- women who are postmenopausal
- pregnancy or planned pregnancy within the period of the trial
- Periodontitis (attachment loss ≥4 mm and probing depths≥5 mm on at least one
interproximal site)
- Any need for immediate dental treatment (can be eligible after completion of
treatment)
- history of hypercalcemia, malabsorption syndrome, abnormal sensitivity to vitamin D or
hypervitaminosis D
- < 3 teeth with bleeding on probing
- < 20 teeth present or <8 interproximal spaces (i.e., papillae) in upper jaw
- mean plaque index > 3
- Current smoking or former smoking with cessation <5 years ago
- regular use of any medication for prevention or treatment of disease (including
Aspirin, NSAIDs, corticosteroids, but NOT including contraceptives)
- Diabetes mellitus
- hypercalcemia (serum calcium > ULN),
- hypocalcemia (serum calcium < ULN),
- hyperparathyroidism (serum PTH concentration > ULN),
- hypoparathyroidism (serum PTH concentration < LLN)
- any cardiac rhythm abnormalities on baseline ECG
- use of tanning beds/unwillingness to abstain from use of tanning beds during study
- planned travel during study period / unwillingness to abstain from travel to the South
or High Altitudes
- unwillingness to abstain from use of any supplements (including vitamin/mineral and
herbal supplements) during study period
We found this trial at
1
site
100 East Newton Street
Boston, Massachusetts 02118
Boston, Massachusetts 02118
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