Vitamin D Supplementation in Estonian Conscripts
Condition: Vitamin D Deficiency; Military Activity; Physical Stress
MeSH terms: Vitamin D Deficiency
Study type: Interventional

Summary: 
      A longitudinal, double-blinded, randomized, trial, with a 10 month follow-up period will be
      conducted between July 2021 to May 2022
    

Detailed description: 
      I DETAILED DESCRIPTION OF THE SUBJECTS AND THEIR RECRUITMENT Four hundred volunteers from the
      2nd Infantry Brigade of the Kuperjanov Infantry Battalion (Võru, Estonia) aged 18-30 are
      invited to participate in this study. To this end, a general meeting will be held at the
      beginning of the conscription. The participants will be given an overview of the study, its
      objectives and methods, all the risks that may be involved, and the potential benefits. The
      meeting will emphasise the voluntary nature of the study and the fact that non-participation
      in the study does not lead to changes in the overall cost of their conscription. Conscripts
      wishing to participate in the study can sign an information sheet and informed consent form
      to participate in the study after the meeting. Based on previous studies (experience of our
      working group in 2014-2017), the participation of about 150-170 conscripts is expected
      (25-30% of the total number).

      Places of the study:

        1. University of Tartu Clinic, Sports Medicine and Rehabilitation Clinic, Sports
           Traumatology Centre, Puusepa 1a, Tartu, 51014

        2. Recruitment of subjects, general medical assessment and completion of questionnaires,
           blood sampling, physical tests, and bone densitometry analysis. Kuperjanov Infantry
           Battalion, 2nd Infantry Brigade (Kose tee 3a, 65603, Võru)

        3. Determination of vitamin D, PTH, and Ca in the blood: Synlab Eesti OÜ, Teguri 37b,
           50107, Tartu

      The questionnaires used in the study will be completed on site at the Kuperjanov Infantry
      Battalion. The subjects are divided into two groups by a computer with double-blind
      randomisation in a 1 : 1 ratio - subjects receiving 4,000 IU of vitamin D or a 100 µg capsule
      (Group I, n = 75-85) and subjects receiving 600 IU or 15 µg vitamin D capsules (Group II, n =
      75-85) of the same shape and colour once a day with breakfast The corresponding capsules are
      pre-prepared in agreement with the manufacturer (HC CLOVER Productos y Servicios, S.Lk) and
      packed in standard jars (100 capsules per jar; a total of three jars with the corresponding
      number of capsules for ten months should be used for the study). Each jar is coded
      individually for each subject in accordance with the randomised groups.

      Serum levels of vitamin D (25(OH)D), s-PTH, s-Ca, and s-iCa are determined in all subjects
      during the visits (SynLab Eesti OÜ, Tartu). Analyses are taken four times during the study
      (visits): July, October, February, and April/May. All analyses are determined at the end of
      the study at the same time to reduce intra-assay variability due to the use of different
      kits.

      For all health-related problems related to the study, as well as other problems related to
      the study, conscripts are consulted by the orthopaedist in charge (Dr Leho Rips). If there
      are any health problems not related to the study, the medical staff of Kuperjanov will inform
      the principal researcher (Dr Leho Rips). The subjects have the right to contact the principal
      researcher directly in case of problems related to the study.

      Exclusion from the study: - refusal of a conscript or withdrawal of consent, departure from
      military unit, force majeure, acute trauma, or illness in the course of conscript requiring
      hospital treatment. All these cases are recorded and taken into account in the subsequent
      analysis.

      II DETAILED DESCRIPTION OF THE STUDY METHODOLOGY

      Anthropometric measurements. The length of the body (LB) is measured with a metal
      anthropometer in a vertical position, the heels are together and the person measuring the
      subject ensures that the lower eyelid and the outer ear canal of the subject are in a
      horizontal plane. To determine body weight (W), the subject should wear as little clothes as
      possible. An electronic scale with a measuring accuracy of ± 0,1 kg is used for the
      measurement. The formula BMI = W / LB [kg/m2] is used to calculate the body mass index.

      Vitamin D in serum ((25(OH)D is determined by chemiluminescence immunoassay (CLIA). (LIAISON
      25 OH Vitamin D TOTAL Assay (REF 310600, DiaSorin Inc, USA)) with a sensitivity of 4 ng/ml
      and an intra-assay variability coefficient (CV) of 0.1-3.8%. Vitamin D levels in the blood
      are determined four times during the study period to explain the effects of strain, Estonian
      climate, and supplementation on serum concentrations (at the beginning of the conscript,
      twice in the middle of the conscript, and in the final phase).

      Calcium (s-Ca), ionised calcium (s-iCa), and parathyroid hormone (s-PTH) are determined from
      blood serum by potentiometry and chemiluminescent immunoassay (CLIA), respectively.

      All blood tests are taken at the same time in the morning before breakfast and during the
      same periods, analogously to vitamin D.

      About 5 to 8 ml of blood is taken during each blood test, a total of 20 to 32 ml. This is
      about 2 tablespoons of blood throughout the study.

      Assessment of knee pain. The visual analogue scale VAS is used where '0' - no pain and '10' -
      maximum pain, associated with the KOOS questionnaire to assess subjective complaints related
      to the knee joint.

      Subjective assessment of knee joint function by the subject. The subjects evaluate the
      subjective complaints and function of the knee joint with a questionnaire (Knee Injury and
      Osteoarthritis Outcome Score, KOOS), which is used to find out their assessment of the
      condition of their knee(s) and how well they can cope with daily activities. It is possible
      to get a maximum of 100 points (no complaints) and a minimum of 0 points, which means extreme
      complaints.

      Hand grip strength is determined by isometric contraction while standing, upper limb away
      from the body, using a hand dynamometer (Lafayette Instrument Co., USA). The studies use
      maximal hand grip strength as an indirect indicator of whole-body muscle strength.

      Subjective assessment of physical activity by the subject. The Baecke Physical Activity
      Questionnaire consists of three parts and is based on a person's subjective assessment of
      their work, sport, and leisure (it is possible to get 1-5 points for each question). To
      interpret the results, the number of points in each subsection and the total number of points
      in the whole questionnaire are given. A similar questionnaire has been used to determine
      physical activity in previous studies in conscripts. IPAQ International Physical Activity
      Questionnaire, which assesses the level of physical activity in the last 7 days.

      The assessment of subjective pain in different regions of the body is done with the Cornell
      Musculoskeletal Discomfort Questionnaires (CMDQ), where the intensity of pain and the region
      of the body can be noted. Pain questionnaire ( to assess pain in different regions of the
      body on a scale from 0 (none) to 10 (maximum possible pain).

      The assessment of subjective health status and health-related quality of life by the subject
      is performed using standard questionnaires SF-36, RAND36, and BDI - Beck Depression
      Inventory. The questionnaires have been validated in Estonia and are valid for identifying
      health-related aspects. The questionnaires are based on the subject's assessment of their
      health aspects. The SF-36 questionnaire identifies the health status with a descriptive
      health profile and is more sensitive than other questionnaires. It also calculates the total
      physical and mental health scores. The BDI questionnaire is based on the assessment of the
      subject concerning aspects related to their mental health.

      Evaluation of emotional well-being and somatic symptom disorder symptoms on the basis of the
      EEK-2 emotional well-being questionnaire and ACR 2010 questionnaires The emotional well-being
      questionnaire is a patient-completed self-assessment scale for identifying major depression
      and anxiety disorders and their adjacent symptoms in the past month. The EEK-2 questionnaire
      consists of 28 statements formulated based on diagnostic criteria and clinical feasibility.
      The answers are on a scale of 0-4 and the subject indicates how much the problem has
      disturbed them in the last month. The ACR 2010 questionnaire is a questionnaire developed and
      validated by the American College of Rheumatology to assess the presence of the somatic
      symptom disorder and non-physical pain (such as fibromyalgia) in subjects.

      Fitness tests. Along with other data, the level of physical training of the conscripts is
      analysed using the standardised Army Physical Fitness Test (APFT), consisting of push-ups,
      sit-ups, and a 2-mile (3.2-km) run. The test has been adapted and used for a long time in the
      Estonian Defence Forces. Based on the results, the total score is calculated.

      Bone density study or densitometry. A mobile DXL machine is used to determine bone density.
      Bone density is determined from the heel bone. Bone density is determined twice during the
      study period on site. Bone density measurement of the heel bone is performed by densitometry
      with a DXL Calscan instrument (Demetech AB, SWE). The measurements are performed at the
      beginning of the study and after about 10 months, just before the end of the conscript. The
      procedure shows the bone density of the subjects. The second study provides an assessment of
      the effects of exercise on the musculoskeletal system.

      Health status monitoring. The health status of conscripts is monitored in the medical centre
      of the Combat Service Support Battalion of the 2nd Infantry Brigade, where records are made
      of the appeals and complaints of the conscripts, the number of days in inpatient care and bed
      rest, and the number of days when a conscript was absent from the conscript due to health
      problems.

      Evaluation of vitamin D content in food rations of the Defence Forces. The average daily
      vitamin D content of the 1-month period of conscription in the daily food ration for
      conscripts is assessed. Based on international analytical data on vitamin D content in food.

      Questionnaire completion and data collection, blood sampling, anthropometric evaluations, and
      health monitoring are performed by the study team.
    

Intervention name(s): Vitamin D3 capsules 4000IU/100µg.; Vitamin D3 capsules 600IU/15µg.
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Vitamin D3 supplementation; Vitamin D3 supplementation
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Triple blinded randomized placebo-controlled study
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Vitamin D supplementation; Conscripts; Military sevice; Physical preformance