Effect of Vitamin D in Patients With Diabetic Peripheral Neuropathy to Alleviate Pain and Improvement of Symptoms
Condition: Diabetic Peripheral Neuropathy
MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies
Study type: Interventional

Summary: 
      Diabetic peripheral neuropathy(DPN) is one of the major complications of diabetes mellitus
      which accelerates the occurrence of ulceration of diabetic foot and amputation of lower
      extremities as well as severely affects the quality of life. The treatment of this condition
      has remained unsatisfactory with a good response to conventional medications. It is now
      evident that vitamin D deficiency is common in diabetic patients and especially in these
      patients diagnosed with diabetic peripheral neuropathy. The present research is therefore
      designed to observe the effect of exogenous administration of vitamin D in diabetic
      peripheral neuropathy patients of Bangladesh.
    

Detailed description: 
      Diabetic peripheral neuropathy is one of the common complications of long-standing diabetes
      mellitus with a prevalence of 30% to 50%. It accelerates the occurrence of ulcers of diabetic
      foot and amputation of lower extremities as well as severely affects the quality of life. The
      treatment of this condition has remained unsatisfactory in spite of a good response to
      conventional medications. Studies showed that Vitamin D3 exerts a neuroprotective effect
      through the production of nerve growth factor (NGF) and neurotrophins. However, some recent
      trials demonstrated that vitamin D3 could be a promising agent in this regard. This proposed
      study was therefore an effort whether there is any role of vitamin D3 in improving symptoms
      of diabetic peripheral neuropathy patients. This study was a randomized, double-blind,
      placebo-controlled trial, conducted in the Department of Pharmacology in collaboration with
      the Department of Endocrinology of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka
      from September 2019 to January 2022. A total of 72 patients suffering from diabetic
      peripheral neuropathy was enrolled according to inclusion and exclusion criteria. A validated
      version of the Michigan Neuropathy Screening Instrument (MNSI) and Visual Analogue Scale
      (VAS) was used to assess peripheral neuropathy. Then the patients were randomly allocated
      into two arms: control and intervention. The patient in the control arm received the standard
      antidiabetic medications plus one placebo capsule weekly orally for 8 weeks starting from the
      day of an initial assessment. On the other hand, the intervention arm received the standard
      antidiabetic medications plus one capsule of vitamin D3 (40,000 IU) weekly orally for 8 weeks
      starting from the day of an initial assessment. Data of HbA1c level was recorded and a blood
      sample was collected to measure serum 25(OH) D level at baseline and after 8 weeks of
      therapeutic intervention. Confirmation of the regular intake of medicine was ensured over the
      telephone, pill count, and from the patient's compliance sheet. After 8 weeks each patient
      was evaluated again using VAS and MNSI tools. Out of 72, 53 patients had completed the study
      and met the criteria for analysis. Therefore, Intention to Treat (ITT) was 72 and Per
      Protocol (PP) treatment was 53. The statistical tests used to analyze the data were the
      chi-square (x2) test, paired t-test, unpaired t-test, and Pearson correlation test. The
      chi-square (x2) test was used to compare categorical data between two groups. The independent
      t-test was used to compare the continuous data between two groups. P-value ≤ 0.05 was
      considered significant. After 8 weeks of treatment, the VAS score of pain in DPN patients in
      the intervention arm reduced significantly (P=0.00) from 5.50 ± 0.64 to 4.23 ± 0.98. In the
      intervention arm, statistically significant improvement was also observed in the MNSI score
      both for the questionnaire (from 8.54 ± 1.15 to 6.00 ± 1.32; P=0.00) and physical assessment
      (from 3.44 ± 1.22 to 2.40 ± 1.06; P=0.00) respectively. Serum 25(OH)D level significantly
      improved (P=0.00) after oral administration of vitamin D3 in the intervention arm from 10.83
      ± 4.47 ng/ml to 17.79 ± 7.53 ng/ml. The reduction observed in HbA1c level in the intervention
      arm (from 8.66 ± 1.39 to 7.25 ± 0.87) was significant (P=0.00). This should be noted that a
      significant reduction of VAS score (P= 0.04) and MNSI questionnaire score (P=0.00) was
      observed in the placebo arm after 8 weeks, though the difference between the reduction
      achieved was significant between placebo and intervention arm (for VAS, P=0.00 and for MNSI,
      P=0.00). However, in the control arm, there was no significant reduction (P=0.69) in MNSI
      physical assessment score. A negative correlation was observed between serum 25(OH) D level
      and VAS (r= -0.1) and MNSI score (r= -0.17) respectively. Oral administration of 40,000 IU
      vitamin D3 weekly for 8 weeks along with standard antidiabetic medications produces a
      significant reduction of the level of pain and other neuropathic symptoms in the patients
      with Diabetic Peripheral Neuropathy.
    

Intervention name(s): Vitamin D3; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Dietary supplement:Vitamin D3
1 capsule of Vitamin D3 (40,000IU) weekly for 8 weeks with antidiabetic drug; 1 capsule weekly for 8 weeks with antidiabetic drug
Other intervention name(s): Cholecalciferol
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Diagnosed case of Type 2 Diabetes Mellitus with peripheral neuropathy
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: DPN; Vitamin D3; MNSI