Vitamin D Supplementation and Sunlight Exposure in Brazilian Women Living in Opposite Latitudes (The D-SOL Study)
Condition: Vitamin D Deficiency
MeSH terms: Vitamin D Deficiency
Study type: Interventional

Summary: 
      There is a consensus that vitamin D deficiency is a public health issue because of its
      implications in several diseases including, osteopenia, osteomalacia, heart disease, diabetes
      (type I and II), inflammatory diseases, multiple sclerosis and rheumatoid arthritis. Studies
      in sunny countries have shown that vitamin D deficiency is a common phenomenon, despite the
      abundance of sunlight in these places, which shows the influence of diet, skin pigmentation,
      cultural habits and also genetic factors on the metabolism of this vitamin. Thus, the study
      hypothesis is that vitamin D supplementation is required to obtain the optimal serum
      concentration in Brazilian people living both in Brazil and in the United Kingdom and that
      this response is dependent on the initial levels, being influenced by sunlight exposure, skin
      pigmentation, diet and polymorphisms of the vitamin D receptor gene. Two controlled,
      randomized, double-blind clinical trials were held (one in the UK and the other in Brazil)
      over a period of 12 weeks, with female subjects, Brazilian, aged 20 to 59 years. The women
      selected were divided into two groups: Placebo Group and Supplemented Group, the latter
      received vitamin D 600 IU. After the analysis of the effect of vitamin D supplementation
      compared to placebo, the investigators propose to analyse genome-wide transcriptomic
      expression in order to associate specific signal transduction and metabolic pathways to
      respective vitamin D responses. and a genetic risk score based on polymorphisms will be
      constructed. The 'systems level' approach will enable us to identify differences in gene
      expression and whether this explains why some individuals are 'good' responders or 'poor'
      responders to vitamin D supplementation. This is the first study that will examine two
      population groups of the same ethnic group and sex, living in different countries, with
      identical design studies. Our results first will determine how important supplementation and
      exposure to sunlight are for the serum level of vitamin D by comparing directly, using the
      same methodology, people living in different latitudes, as well as the genetic influence on
      the response to supplementation. The data will also provide both countries key data about the
      need to reconsider new revisions to dietary recommendations for vitamin D in adults.
    

Detailed description: 
      During this study the subjects were asked to visit the Clinical Investigation Unit, FHMS,
      University of Surrey in the UK or the Research Clinic, Faculty of Nutrition, Federal
      University of Goiás in Brazil, on two occasions, at the beginning of the study for baseline
      measurements and at the conclusion of the study. The investigators examined four to eight
      fasted subjects per study morning. Trial visits lasted approximately 45-60 minutes each and
      took place in the morning (7am-11am). Participants were offered refreshments at the end of
      their appointment.

      If participants wished to be screened for participation in the study, they would receive the
      Participant Information Sheet and then be checked against the study inclusion and exclusion
      criteria using a 'Screening Questionnaire' , administered by a member of the D-SOL Research
      Team by phone or self-reported by email.

      Baseline visit:

      If eligible, participants were invited for the baseline visit. At this visit, they were first
      given time to discuss the Participant Information Sheet and any questions they may have
      regarding the study. Informed consent was discussed and participants were asked to sign the
      consent form, and offered a copy to keep for themselves.

      Baseline procedures:

        -  Health and Lifestyle questionnaire administered by a member of the D-SOL Research Team.

        -  Anthropometrics and blood pressure measured, and fasted blood sample taken (serum 25OHD
           levels, 1,25-dihydroxy vitamin D, serum calcium, albumin, parathyroid hormone,
           C-terminal telopeptide (CTX) ≈25ml) with an additional ≈10 ml for genetic profiling and
           ≈15 for storage for future measurements of nutritional markers.

        -  pQCT scan of the non-dominant forearm (UK trial) or dual energy x-ray absorptiometry
           (DEXA) scan (Brazil trial).

        -  Bioelectrical impedance analysis (BIA) for body composition.

        -  Provision of randomly assigned daily supplement (30 days' supply), food diaries and
           sunlight dosimeters and sunlight exposure diary to be returned at 12 week visit.
           Follow-up appointment details arranged.

      Final visit

        -  Final adverse event/compliance interview completed with investigator.

        -  Daily outdoor exposure diary, food diary and sunlight dosimeter received from
           participant and checked for consistency at visit.

        -  Anthropometrics and blood pressure measured, and blood sample taken (serum 25OHD levels,
           1,25-dihydroxy vitamin D, serum calcium, albumin, parathyroid hormone, C-terminal
           telopeptide (CTX) ≈25ml) with an additional ≈10 ml for genetic profiling and ≈15 for
           storage for future measurements of nutritional markers.

        -  Bioelectrical impedance analysis (BIA) for body composition.

      DNA profiling procedure - After 12 weeks: Selection of participant samples encompassing the
      best and worst supplementation-responders in each group, subject to previous consent form
      singed by participant. Vitamin D related genes will be genotyped in DNA isolated from the
      study blood samples, DNA will be extracted and vitamin D polymorphisms will be determined by
      University of Surrey's genetic labs.

      A trained phlebotomist took the blood samples required as part of the trial protocol. Medical
      cover was available at all times.

      Throughout the duration of the trial, the participants were contacted via telephone on a
      fortnightly basis to discuss any issues with any adverse event and compliance and to maintain
      good communication with the participants. In the case of a serious adverse event (SAE) this
      would be recorded and reported it to both the Sponsor (University of Surrey) and the Surrey
      Ethics Committee.

      The final interview was completed at the final study visit. Participants have also been asked
      to return any supplements that were missed to confirm compliance.

      For University of Surrey participants: A peripheral quantitative computed tomography (pQCT)
      scan was performed on the participant's non-dominant forearm at the baseline visit, to
      measure volumetric bone mineral density at the 4% and 66% radial site. This will allow for
      separate measurements of trabecular volumetric bone mineral density (vBMD) and trabecular
      area (4% site) and cortical vBMD and cortical area (66% site), as well as strength strain
      index, a measure of bone strength. pQCT also measures bone geometry alongside bone density.
      Therefore the muscle cross sectional area can be determined, which is a measure of muscle
      force, to which bone strength is adapted to. One scan was performed at baseline only and
      effective exposure doses were between ~1.5-1.8uSv.

      For Federal University of Goiás participants: Body composition (absolute and relative amount
      of lean and fat mass), whole body mineral density and lower spine and femur bone mineral
      density was measured with the use of DEXA (located at the Nutrition Clinic based at the
      Federal University of Goiás), at baseline only. Two scans were performed at baseline for each
      participant: one to assess the whole body mineral density and body composition, and the other
      to specifically assess fracture risk by scanning the spine and femoral head. Effective
      exposure doses for theses scans are ~8uSv and ~4uSv respectively.

      Results of the body composition, vitamin D status and dietary intake from the self-reported
      food diaries will be made available to the subjects upon request. The results from the blood
      analysis will be reported to the subject if there are any health concerns raised. If the
      results are within healthy ranges the participants will not be contacted unless they
      specifically request for this information. The investigators will not be contacting their
      general practitioner (GP) if there are any concerns raised in the study however the
      investigators will stress that they should contact their GP themselves to discuss the
      results.

      The trial was conducted in compliance with the principles of the Declaration of Helsinki
      (2008), the principles of Good Clinical Practice and in accordance with The Medicines for
      Human Use (Clinical Trials) Regulations 2004 and Amended Regulations 2006.

      Detailed protocol and supporting documents were submitted for review by the University of
      Surrey Ethics Committee and the Federal University of Goiás, Brazil. The study received
      favourable ethical opinion from both Committees prior to commencing the study. Annual
      progress reports and a final report will be submitted to the ethics committees as defined in
      their respective regulations.
    

Intervention name(s): Vitamin D supplementation; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Vitamin D supplementation of 600 IU daily for 12 weeks; rice flour with no vitamin D
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Two controlled, randomized, double-blind clinical trials developed and undertaken (one in Brazil and the other in the UK) with an intervention period of 12 weeks. The women selected were randomly divided into two groups: Placebo Group and Supplemented Group, the latter will receive 600UI of vitamin D, in each country. Groups (arms): Placebo UK trial; Vitamin D UK trial; Placebo Brazuk trial; Vitamin D Brazil trial.
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Vitamin D; Supplementation; Sunlight