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High vs Low Dose Vitamin D in Patients With Diabetic Peripheral Neuropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04377399
Recruitment Status : Completed
First Posted : May 6, 2020
Last Update Posted : May 6, 2020
Sponsor:
Collaborator:
Tameside Hospital NHS Foundation Trust
Information provided by (Responsible Party):
Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

Brief 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.


Condition or disease Intervention/treatment Phase
Diabetes Type 2 Diabetic Neuropathies Vitamin D Deficiency Drug: Vitamin D Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: High-dose Vitamin D Supplementation Reduces Inflammation and Improves Microcirculation in Patients With Diabetic Peripheral Neuropathy
Actual Study Start Date : January 10, 2018
Actual Primary Completion Date : June 20, 2019
Actual Study Completion Date : January 25, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Vitamin D

Arm Intervention/treatment
Active Comparator: high dose
vitamin D (40,000 IU weekly) for 24 weeks
Drug: Vitamin D
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

Active Comparator: Low dose
vitamin D (5,000 IU weekly) for 24 weeks
Drug: Vitamin D
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




Primary Outcome Measures :
  1. Microcirculation [ Time Frame: Baseline and 24 weeks ]
    Assessment of microcirculatory changes using laser doppler


Secondary Outcome Measures :
  1. Interleukins [ Time Frame: Baseline and 24 weeks ]
    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

  2. Tumor necrosis factor-α (TNFα) [ Time Frame: Baseline and 24 weeks ]
    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)

  3. Neuropathy disability score [ Time Frame: Baseline and 24 weeks ]
    Using standard scoring systems and questionnaires. Scoring is: Neuropathy disability score (0-10),

  4. Pain score [ Time Frame: Baseline and 24 weeks ]
    Patients will be asked to score pain on a visual analog scale 0-10 with 10 being the worst pain ever

  5. Neuropathic symptom score [ Time Frame: Baseline and 24 weeks ]
    This will be scored using standard questionnaire 0-9



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04377399


Locations
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Russian Federation
Almazov National Medical Research Centre
Saint Petersburg, Russian Federation, 197143
Sponsors and Collaborators
Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
Tameside Hospital NHS Foundation Trust
Investigators
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Principal Investigator: Tatiana Karonova, PhD Almazov National Medical Research Centre
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Responsible Party: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
ClinicalTrials.gov Identifier: NCT04377399    
Other Study ID Numbers: AAAA-A18-118042390157-9
First Posted: May 6, 2020    Key Record Dates
Last Update Posted: May 6, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Diabetic Neuropathies
Vitamin D Deficiency
Diabetes Mellitus, Type 2
Neuromuscular Diseases
Nervous System Diseases
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vitamin D
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents