High vs Low Dose Vitamin D in Patients With Diabetic Peripheral Neuropathy
High-dose Vitamin D Supplementation Reduces Inflammation and Improves Microcirculation in Patients With Diabetic Peripheral Neuropathy
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.
Panoramica dello studio
Stato
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 4
Contatti e Sedi
Luoghi di studio
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Saint Petersburg, Federazione Russa, 197143
- Almazov National Medical Research Centre
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- males and females with T2DM aged 18 to 65 years
- diabetes duration ≥5 years,
- HbA1c <9%,
- stable hypoglycemic,
- hypotensive and hypolipidemic therapy
- neurological deficit 4 points and more according to the neuropathy disability score (NDS).
Exclusion Criteria:
- patients with type 1 diabetes
- hypothyroidism
- glomerular filtration rate (GFR) <45 ml/min/1.73 m2
- current and former smokers
- obliterating atherosclerosis
- diabetic foot or Charcot osteoarthropathy
- inflammatory joint diseases
- oncological diseases
- ongoing infectious diseases or in the preceding four weeks
- alcohol and drug addiction
- history of В12 deficiency
- anemia or current therapy with vitamin B12
- regular use of glucocorticoids
- vitamin D supplements
- anticoagulants
- antidepressants
- tricyclic antidepressants
- anticonvulsants
- opiates
- non-steroidal anti-inflammatory drugs
- vasoprotective and microcirculation correctors
- alpha lipoic acid
- group B vitamins.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Comparatore attivo: high dose
vitamin D (40,000 IU weekly) for 24 weeks
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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
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Comparatore attivo: Low dose
vitamin D (5,000 IU weekly) for 24 weeks
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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
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Microcirculation
Lasso di tempo: Baseline and 24 weeks
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Assessment of microcirculatory changes using laser doppler
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Baseline and 24 weeks
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Interleukins
Lasso di tempo: Baseline and 24 weeks
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Serum interleukins (IL) will be determined by enzyme-linked immunosorbent assay (Bio-Rad 680 Microplate Reader, USA) using the appropriate sets of reagents for enzyme immunoassay to determine the concentration of IL-1β (reference values 0-5.0 pg/ml), IL-6 (reference values 0-7.0 pg/ml), IL-10 (reference values 0-9.1 pg/ml), (Vector-Best, Novosibirsk, Russia) compared from baseline
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Baseline and 24 weeks
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Tumor necrosis factor-α (TNFα)
Lasso di tempo: Baseline and 24 weeks
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Tumor necrosis factor-α (TNFα) will be determined by enzyme-linked immunosorbent assay (Bio-Rad 680 Microplate Reader, USA) using the appropriate sets of reagents for enzyme immunoassay to determine the concentration of TNFα (reference values 0-8.21 pg/ml) (Vector-Best, Novosibirsk, Russia)
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Baseline and 24 weeks
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Neuropathy disability score
Lasso di tempo: Baseline and 24 weeks
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Using standard scoring systems and questionnaires.
Scoring is: Neuropathy disability score (0-10),
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Baseline and 24 weeks
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Pain score
Lasso di tempo: Baseline and 24 weeks
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Patients will be asked to score pain on a visual analog scale 0-10 with 10 being the worst pain ever
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Baseline and 24 weeks
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Neuropathic symptom score
Lasso di tempo: Baseline and 24 weeks
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This will be scored using standard questionnaire 0-9
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Baseline and 24 weeks
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Collaboratori e investigatori
Collaboratori
Investigatori
- Investigatore principale: Tatiana Karonova, PhD, Almazov National Medical Research Centre
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Disturbi del metabolismo del glucosio
- Malattie metaboliche
- Malattie del sistema nervoso
- Malattie del sistema endocrino
- Complicanze del diabete
- Diabete mellito
- Disturbi della nutrizione
- Malattie neuromuscolari
- Avitaminosi
- Malattie da carenza
- Malnutrizione
- Diabete mellito, tipo 2
- Malattie del sistema nervoso periferico
- Carenza di vitamina D
- Neuropatie diabetiche
- Effetti fisiologici delle droghe
- Micronutrienti
- Vitamine
- Agenti di conservazione della densità ossea
- Vitamina D
Altri numeri di identificazione dello studio
- AAAA-A18-118042390157-9
Piano per i dati dei singoli partecipanti (IPD)
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Informazioni su farmaci e dispositivi, documenti di studio
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