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

May 5, 2020 updated by: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
68

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Saint Petersburg, Russian Federation, 197143
        • Almazov National Medical Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Microcirculation
Time Frame: Baseline and 24 weeks
Assessment of microcirculatory changes using laser doppler
Baseline and 24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Baseline and 24 weeks
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)
Baseline and 24 weeks
Neuropathy disability score
Time Frame: Baseline and 24 weeks
Using standard scoring systems and questionnaires. Scoring is: Neuropathy disability score (0-10),
Baseline and 24 weeks
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
Baseline and 24 weeks
Neuropathic symptom score
Time Frame: Baseline and 24 weeks
This will be scored using standard questionnaire 0-9
Baseline and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Tameside Hospital NHS Foundation Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tatiana Karonova, PhD, Almazov National Medical Research Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 10, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 20, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 25, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 29, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 6, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 6, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AAAA-A18-118042390157-9

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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