Vitamin D and Muscle Strength and Surface (Electromyography) EMG
Condition: Vitamin D Deficiency
MeSH terms: Vitamin D Deficiency
Study type: Interventional
Phase: Phase 3

Summary: 
      Vitamin D deficiency is widely prevalent in India. Serum 25(OH)D levels are <20 ng /ml in up
      to 90% of them. Recently, in a randomized control trial, investigators have shown that dual
      cholecalciferol and calcium supplementation lead to significant improvement in hand grip
      strength and distance covered during six minutes walk test. Present study is being taken to
      further understand the functional significance of 25(OH)D in terms of its effect on Skeletal
      muscle strength including surface electromyography (EMG) in a larger cohort involving
      approximately 200 subjects. The impact of calcium and vitamin D supplementation would be
      assessed by supplementing them alone and in combination. Besides, the investigators would
      also assess impact of above supplementation on Th1/Th2 cytokines expression in the peripheral
      mononuclear cells.
    

Detailed description: 
      Vitamin D is an essential nutrient that plays an important role in calcium metabolism and
      bone health. In recent years, biomarkers like PTH, calcium absorption have been used to
      define relevant biological indices of vitamin D nutritional status. Several studies from
      India have shown wide prevalence of vitamin D deficiency (VDD) in India. Goswami et al
      studied serum 25 (OH)D levels and its functional significance in apparently healthy subjects
      residing in Delhi and showed low serum 25(OH)D values in all the groups (Am J Clin Nutr
      2000). Its functional significance is currently under evaluation.

      Relevant studies assessing functional significance of VDD in Asian Indians are summarized
      below (Am J Clin Nutr 2000).

      A) Goswami et al while reporting low serum 25(OH) D concentrations in healthy subjects in
      Delhi, showed a higher serum PTH levels & significant inverse relation between serum 25(OH) D
      and PTH levels ( r = -0.6303, p < 0.001) in all the three groups (soldiers, physicians &
      nurses, depigmented persons) studied in winter (Am J Clin Nutr 2006) B) Effects on BMD
      Recently,we have analyzed relationship between BMD and serum 25(OH) D in 105 apparently
      healthy Asian Indian. The cohort of 105 subjects was split into 2 groups at a serum 25(OH) D
      cutoff of 9.0 ng/mL. The mean serum iPTH was significantly higher in the group 1 (<9.0
      ng/ml)than in the group 2 subjects (53.1±31.3 and 39.3±17.5 pg/mL, respectively; P=0.012).The
      mean BMD values of the total hip, including femoral neck, trochanter, and intertrochanter,
      were significantly (P = 0.001) lower in group 1 than in group 2.

      C) Effect of VDD on intestinal calcium absorption in Asian Indians with chronic
      hypovitaminosis D and its change after cholecalciferol supplementation was studied recently
      at our Department of Endocrinology and Metabolism. Study subjects were 29 apparently healthy
      volunteers [17 M, 12 F, mean (SD) age = 28.4 ± 6.4 year] with low serum 25(OH)D levels [mean
      (SD) = 7.6 ± 4.8 ng/ml]. Intestinal calcium absorption was assessed by 'calcium load test'
      (PAK test) (10) using 1 gm of oral elemental calcium load before and after (n = 26)
      supplementation with oral cholecalciferol (60,000 IU/week for eight weeks). This study showed
      that the vitamin D Deficiency is physiologically relevant in terms of intestinal calcium
      absorption in Asian Indians (Journal of Human Nutrition and dietetics 2010).

      Recently in a randomized control trial we have shown significant improvement in the muscle
      strength and walking distance after dual supplementation with cholecalciferol and calcium
      (Clin Endocrinol 2010). In the current study we plan to study this aspect further by
      recruiting four groups to study the effect of calcium and vitamin D supplementation alone or
      in combination as a dual supplementation. Baseline evaluation (Before vitamin D
      supplementation) would include serum total calcium, inorganic phosphorus, alkaline
      phosphatase, intact PTH and 25(OH) D assays, hand grip muscle strength and surface EMG
      testing. Hand grip would be done will be done using a computerized dynamometer in the
      Department of Physical Medicine and Rehabilitation under the guidance of Professor U Singh,
      Head, Department of Physical Medicine & Rehabilitation, AIIMS. Handgrip strength will be
      measured in right hand by dynamometer. The average of two measurement of grip strength will
      be used for analysis (in kg).

      The physical performance will be tested by performing 6 - minute walk test using standard
      protocol and results will be interpreted in terms of 6 minute walk distance in meters and
      degree of shortness of breath using modified Borg dyspnea scale.

      The mRNA expression Th1 and Th2 cytokines would be assessed in the PBMC drawn from 5 ml of
      the peripheral blood using the real time PCR.

      Vitamin D supplementation

      All the subjects will be randomized into three treatment groups and one placebo group in a
      double blind manner. Random code would be generated by a investigator, who will not be
      involved in distribution of medicines and assessment of the muscle strength Active drug would
      be calcium (two tablets of calcium carbonate each containing 500 mg of elemental calcium/day,
      and 60,000 IU of cholecalciferol/week obtained from the commercial source. The inactive drug
      would be lactose containing identical placebo obtained from the same source. All study
      subjects will be provided with packets containing four sachets of cholecalciferol (each
      containing 60000 IU vitamin D3; Cadila Pharmaceutical, India) /placebo; and sixty tablets of
      calcium carbonate (500mg elemental calcium & 250 IU vitamin D3; Elder Pharmaceutical,
      India)/placebo. First dose will be supervised. Subjects will be counseled for daily intake of
      two tablets of calcium carbonate and weekly intake of a cholecalciferol sachet and follow up
      at completion of 4 weeks. Similar packets will be given after 4 weeks of follow up. Drug
      compliance will be assessed by counting the empty sachets. After eight week subjects will be
      provided daily two tablets of calcium carbonate containing 500 mg elemental calcium each and
      two sachets of cholecalciferol every month for four months.

      Assessment at 8 weeks and 6 months would include serum intact PTH & 25(OH) D levels
      estimation, skeletal muscle strength testing, and 6 minute walk test and Th1/Th2 analysis

      Safety of Proposed Interventions Cholecalciferol dose of 60000 IU/week × 8 weeks has been
      considered safe to be used in healthy subjects, as shown in our recent studies.
    

Intervention name(s): Cholecalciferol; Calcium Carbonate; cholecalciferol and calcium carbonate; lactose placebo; lactose granules and tablets
Intervention type(s): Drug; Drug; Drug; Other; Other
Intervention description(s): 60,000 IU/week for ist eight weeks followed by 60,000 IU every 15 days for four months; two tablets of calcium carbonate daily containing 1 gm of elemental calcium for six months; 60,000 IU of cholecalciferol for first eight weeks and then 60,000IU for next four months along with 1 gm of elemental calcium daily for six months; similar number of granules and tablets as active group; one sachet every week for eight weeks followed by two sachets every month along with two lactose tablets daily
Other intervention name(s): Vitamin D; Calcium; vitamin D and calcium carbonate; lactose
Intervention MeSH terms: Calcium, Dietary; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Calcium Carbonate; Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Health Services Research