High vs Low Dose Vitamin D in Patients With Diabetic Peripheral Neuropathy
Condition: Diabetes Type 2; Diabetic Neuropathies; Vitamin D Deficiency
MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies; Vitamin D Deficiency; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      Aim. To assess the effect of different doses of vitamin D supplementation on peripheral
      neuropathy in patients with type 2 diabetes mellitus (T2DM).

      68 patients with T2DM and peripheral neuropathy will be randomized into two treatment groups:
      cholecalciferol 5,000 IU once/week and cholecalciferol 40,000 IU once/week orally for 24
      weeks. Severity of neuropathy (neuropathy symptom score (NSS), neuropathy disability score
      (NDS), visual analog scale (VAS)), body mass index (BMI), glycated hemoglobin (HbA1c),
      25-hydroxycalciferol (25(OH)D), parathyroid hormone (PTH), serum interleukins (IL) 1β, 6 and
      10, C-reactive protein, tumor necrosis factor α and microcirculation (MC) parameters assessed
      before and after treatment. The initial and final indicators of the skin blood flow (M, σ,
      Kv) and MC parameters after postural and occlusal tests by laser Doppler flowmetry (LDF).
      Sixteen subjects without diabetes will represent the control group.
    

Detailed description: 
      It is well known that vitamin D deficiency along with type 2 diabetes mellitus (T2DM) is a
      modern pandemic. Development of microvascular complications in T2DM worsens both the
      prognosis and the patients' quality of life. There is increasing evidence of a possible
      contribution of vitamin D deficiency to the pathogenesis of diabetes and its complications.
      Large-scale studies have shown 40% increased risk of developing diabetes in individuals with
      a reduced 25(OH)D level. A recent interventional prospective study demonstrated no decrease
      in the risk of T2DM development in patients with prediabetes after two-year treatment with
      4,000 IU of vitamin D per day. But, some experts suggested that 4,000 IU is not sufficient
      supplementation dose for patients with already existing impaired glucose metabolism and on
      the other hand most study participants had normal basal 25(OH)D level. Along with
      immune-mediated mechanisms, microcirculation deterioration in patients with diabetes has been
      found to play an important role in the pathogenesis of microvascular complications including
      peripheral neuropathy (DPN).

      It is believed that vitamin D deficiency also plays a role in the progression of DPN. Thus,
      the correction of vitamin D deficiency in patients with T2DM is becoming increasingly
      attractive for the prevention and treatment of microvascular complications. However, the
      question of the required vitamin D dose and the treatment duration remain highly debatable.
      The aim of this study was to assess the effect of therapy with different doses of
      cholecalciferol for 24 weeks on clinical manifestations of peripheral neuropathy,
      inflammatory markers, and parameters of microcirculation in patients with T2DM.

      Patients and Methods: Baseline characteristics will be recorded for all patients including
      Height, weight, BMI, diabetes status and biochemical parameters. All will be repeated at 24
      weeks. Blood will be collected after an overnight fast and stored at -20 degrees until
      analysis.

      Patients will be recruited from the Almazov Research centre, St Petersburg, Russia
      Federation.

      68 patients with T2DM and peripheral neuropathy will be randomized into two treatment groups:
      cholecalciferol 5,000 IU once/week and cholecalciferol 40,000 IU once/week orally for 24
      weeks. Severity of neuropathy (neuropathy symptom score (NSS), neuropathy disability score
      (NDS), visual analog scale (VAS)), body mass index (BMI), glycated hemoglobin (HbA1c),
      25-hydroxycalciferol (25(OH)D), parathyroid hormone (PTH), serum interleukins (IL) 1β, 6 and
      10, C-reactive protein, tumor necrosis factor α and microcirculation (MC) parameters assessed
      before and after treatment. The initial and final indicators of the skin blood flow (M, σ,
      Kv) and MC parameters after postural and occlusal tests by laser Doppler flowmetry (LDF).
      Sixteen subjects without diabetes will represent the control group.
    

Intervention name(s): Vitamin D
Intervention type(s): Drug
Intervention description(s): Patients will be randomised to receive either high dose vitamin D (40,000 IU weekly) or low dose vitamin D (5,000 IU weekly) for 24 weeks
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment