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Efficacy and safety of high-dose intramuscular vitamin D2 injection in type 2 diabetes mellitus with distal symmetric polyneuropathy combined with vitamin D insufficiency: study protocol for a multicenter, randomized, double-blinded, and placebo-controlled trial.

  • 2023-07-07
  • Frontiers in endocrinology 14
    • Tao Chen
    • Xiaoyan Xing
    • Lihua Huang
    • Mei Tu
    • Xiaoli Lai
    • Shidi Wen
    • Jin Cai
    • Shenglong Lin
    • Youping Zheng
    • Yuehui Lin
    • Lijuan Xu
    • Yuwen Qiu
    • Lumin Qiu
    • Yuebo Xu
    • Peiwen Wu

Study Design

Type
Randomized Controlled Trial (RCT)
Population
patients with T2DM and DSPN combined with vitamin D insufficiency
Methods
multicenter, randomized, double-blinded, and placebo-controlled trial; intramuscular injection of vitamin D2 or placebo monthly for 3 months
Blinding
Double-blind
Duration
3 months

Background

Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of type 2 diabetes mellitus (T2DM). DSPN may lead to more serious complications, such as diabetic foot ulcer, amputation, and reduced life expectancy. Observational studies have suggested that vitamin D deficiency may be associated with the development of DSPN in T2DM. However, interventional studies have found that low-dose vitamin D supplementation does not significantly improve neuropathy in DSPN. This study aims to evaluate the efficacy and safety of intramuscular injection of high-dose vitamin D (HDVD) in T2DM with DSPN combined with vitamin D insufficiency.

Methods and analysis

We will conduct a multicenter, randomized, double-blinded, and placebo-controlled trial in four large hospitals. All eligible participants will be randomly assigned to either the vitamin D2 supplement or placebo control group and injected intramuscularly monthly for 3 months. Additionally, anthropometric measurements and clinical data will be collected at baseline and 3 months. Adverse events will be collected at 1, 2, and 3 months. The primary outcome measure is the change in the mean Michigan Neuropathy Screening Instrument (MNSI) score at baseline and 3 months post-intervention. We will use the gold-standard liquid chromatography-tandem mass spectrometry method to distinguish between 25(OH)D2 and 25(OH)D3 levels. The MNSN score before the intervention will be used as a covariate to compare the changes between both groups before and after the intervention, and the analysis of covariance will be used to analyze the change in the MNSI score after HDVD supplementation.

Discussion

Glycemic control alone does not prevent the progression of DSPN in T2DM. Some studies have suggested that vitamin D may improve DSPN; however, the exact dose, method, and duration of vitamin D supplementation are unknown. Additionally, neuropathy repair requires HDVD supplementation to sustain adequate vitamin D levels. This once-a-month intramuscular method avoids daily medication; therefore, compliance is high. This study will be the first randomized controlled trial in China to analyze the efficacy and safety of HDVD supplementation for patients with T2DM and DSPN and will provide new ideas for pharmacological research and clinical treatment of diabetic neuropathy.

Clinical trial registration

https://www.chictr.org.cn/, identifier ChiCTR2200062266.

Research Insights

  • Vitamin D2→Reduced Michigan Neuropathy Screening Instrument Score

    This study aims to evaluate the efficacy and safety of intramuscular injection of high-dose vitamin D (HDVD) in T2DM with DSPN combined with vitamin D insufficiency.

    Effect
    Beneficial
    Effect size
    Small
    Dose
    high-dose intramuscular injection monthly for 3 months

Adverse Events Reported

  • Vitamin D2→Overall tolerability

    Adverse events will be collected at 1, 2, and 3 months.

    Finding
    Reported
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