Vitamin D Treatment for Painful Diabetic Neuropathy
Condition: Diabetic Neuropathy
MeSH terms: Diabetic Neuropathies
Study type: Interventional

Summary: 
      The main objective of the study is to assess the effect of vitamin D treatment on painful
      diabetic neuropathy in Pakistan.

      This is a prospective study of diabetic patients with a DN score ≥ 4, administered a single
      dose of 600,000 IU of Vitamin D.

      All diabetic patients (type 1 and type 2) at the screening visit were considered eligible to
      participate in the study. The change in painful diabetic neuropathy scores was assessed using
      DN4 Neuropathic Pain Diagnostic Questionnaire and SF - MPQ for all participants at each
      visit.
    

Detailed description: 
      Background Painful diabetic neuropathy (DPN) is common in patients with long-standing
      diabetes mellitus. The prevalence of neuropathy approaches 50% in those with diabetes for 25
      years. Among patients with neuropathy, 11.6% with type 1 diabetes and 32.1% with type 2
      diabetes have neuropathic pain. In our recent observational study of a large cohort of
      diabetic patients from primary care in northwest England (n = 15,692), painful diabetic
      neuropathy (PDN), assessed using the neuropathy symptom score (NSS) and neuropathy disability
      score (NDS) (NSS >/=5 and NDS >/=3) was 21%, and the prevalence of painful symptoms (NSS
      >/=5) was 34%. Despite less neuropathy in South Asians (14%) compared to Europeans (22%) (P <
      0.0001), painful symptoms were greater in South Asians (38 vs. 32%, P < 0.0001) and they
      maintained a 50% increased risk of painful neuropathy symptoms (P < 0.0001).

      The potential for an association between vitamin D and a beneficial effect on neuropathy is
      based on experimental data which has shown that vitamin D3 can upregulate NGF and the
      products of its neuronal target genes resulting in an improvement in experimental diabetic
      neuropathy. Vitamin D insufficiency has recently been associated with retinopathy and
      self-reported peripheral neuropathy symptoms even after adjusting for demographic factors,
      obesity, comorbidities, use of medications for neuropathy and diabetes duration and glycemic
      control. Of course, there may be some overlap between the symptoms associated with vitamin D
      deficiency and diabetic neuropathy, which may partly explain the excess painful symptoms we
      have observed in Asians, particularly as the latter have excess vitamin D deficiency.

      The preliminary data suggests there is an urgent need to undertake a blinded
      placebo-controlled randomised trial of vitamin D3 in the treatment of diabetic peripheral
      neuropathy.

      Aims:

        -  To see the association of Serum Vitamin D3 levels in type 2 diabetic subjects with
           Painful neuropathy

        -  Effect of intervention through injectable Vitamin D3 on Painful diabetic neuropathy
           Study Design The study is a single centre, single (patient)-blinded, evaluation of
           injectable cholecalciferol in the treatment of painful diabetic neuropathy.

      Study Drug: Injectable cholecalciferol (inj. Vitamin D3 600,000 IU).

        1. Sample size = 165 type 2 diabetic subjects

        2. Recruitment time = 12 weeks

        3. Treatment duration = 12 weeks

      Data Analysis and Statistical Considerations:

      The normality of the data will be assessed and if the data are severely non-normal, log
      transformations will be considered. The primary analysis will compare the change from
      baseline without an alpha adjustment for the multiple comparisons. Comparisons within each
      treatment group across time will also be considered. The analysis will be performed with Last
      Observation Carried Forward (LOCF).

      Assessment during the Treatment Period:

        -  Change from baseline in DN4

        -  Change from baseline in SF-MPQ

        -  Change from baseline in NeuroQol

        -  Change from baseline in serum 25 (OH) D, serum corrected calcium; parathyroid hormone,
           serum phosphate; serum ALP

        -  Change from baseline in HbA1c; fasting glucose; CBC, urea, creatinine, electrolytes,
           urine DR, fasting lipid profile
    

Intervention name(s): cholecalciferol
Intervention type(s): Drug
Intervention description(s): Effect of Vitamin D on the symptoms of diabetic neuropathy
Other intervention name(s): Vitamin D3
Intervention MeSH terms: Vitamin D; Cholecalciferol
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care