Dose-dependent Anti-inflammatory Effects of Vitamin D in a Human Gingivitis Model
Condition: Gingivitis
MeSH terms: Gingivitis
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): vitamin D3; Placebo
Intervention type(s): Drug; Other
Intervention description(s): oral supplementation once per day for 12 weeks of different daily doses: 500 IU, 2500 IU, or 5000 IU after abstaining from oral hygiene measures (brushing, flossing or antiseptic mouth rinses) for a period of 4 weeks to allow accumulation of plaque and development of experimental gingivitis.; oral supplementation once per day for 12 weeks of a sugar pill after abstaining from oral hygiene measures (brushing, flossing or antiseptic mouth rinses) for a period of 4 weeks to allow accumulation of plaque and development of experimental gingivitis.
Other intervention name(s): cholecalciferol; sugar pill
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: vitamin D; gingivitis; periodontal disease; inflammation