Condition category
Nutritional, Metabolic, Endocrine
Date applied
26/11/2019
Date assigned
02/12/2019
Last edited
02/12/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Background and study aims
Vitamin D is a fat-soluble vitamin that our body gets mainly when we expose the skin to sunlight. Its primary role is to maintain adequate blood levels of calcium and phosphorus needed for keeping our bones healthy. Beside its skeletal effects, increasing evidence shows that vitamin D could play an important role in developing some chronic conditions like type 2 diabetes mellitus (T2DM). Patients with T2DM usually have a lack of vitamin D but it is still unknown if this is a coincidence or low levels of vitamin D may cause the disease. This could mean that giving vitamin D to patients with T2DM might help them in better control of their disease. Unfortunately, there is a lack of evidence to clarify if vitamin D could be used with the standard pharmacological treatment. In order to help clarify its role in treating patients with T2DM the aim of this study is to compare patients using vitamin D supplements and antidiabetic drugs with patients using antidiabetic drugs only.

Who can participate?
Patients from Primary Health Care Center Podgorica, diagnosed with T2DM, aged 30 and older with good metabolic control of the disease (HbA1c≤7 %)

What does the study involve?
Participation in this study is completely voluntary. Half of the participants are randomly allocated to receive the vitamin D supplement in addition to standard antidiabetic treatment (metformin and lifestyle advice) while the other half of the participants continue using antidiabetic treatment only. Vitamin D supplements are given in the form of oil drops (Vigantol oil). Dosing is carried out according to the available clinical practice guideline in relation to vitamin D baseline levels. If their starting levels of vitamin D are 50 nmol/L or less participants are asked to take 15 drops of Vigantol oil daily (equal to 50,000 IU weekly) for the first 3 months, and 4 drops of Vigantol oil (equal to 14,000 IU weekly) for the next 3 months. Participants whose vitamin D levels are more than 50 nmol/L are asked to take 4 drops of Vigantol oil (equal to 14,000 IU weekly) during their participation in the study (6 months). All participants are given recommendations regarding nutrition and sunlight exposure, where the compliance is carefully controlled by medical staff. During the study all participants are asked to provide a small amount of blood at the start of the study and after 3 and 6 months. The purpose of the blood test is to check each participant’s vitamin D levels when they enter the study and again at the 3 and 6 month assessment points. From the same blood sample the researchers also check general blood chemistry, including calcium levels and hormones that are linked to glycemic control (insulin) as well as oxidative stress markers. To monitor their physical health the researchers ask each participant’s permission to measure their weight, height, waist and blood pressure measurements at the start of the study and after 3 and 6 months.

What are the possible benefits and risks of participating?
Participants using vitamin D supplements will have benefit for their bone and muscle health. The researchers will closely monitor their vitamin D and calcium levels in blood in order to prevent the negative effects of excessive vitamin D supplementation. All participants will benefit from their close and regular contact with the medical team regarding their disease control.

Where is the study run from?
Primary Health Care Center Podgorica (Montenegro)

When is the study starting and how long is it expected to run for?
April 2018 to December 2018

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Dr Milena Cojić
milenac@ac.me

Trial website

Contact information

Type

Public

Primary contact

Dr Milena Cojic

ORCID ID

https://orcid.org/0000-0002-4395-0626

Contact details

ul.Bracana Bracanovica 34
Podgorica
81000
Montenegro
+382 (0)69160909
milenac@ac.me

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

05/01-E.K.-5989/1

Study information

Scientific title

The effects of vitamin D supplementation on insulin resistance, Castelli Risk Index I and TG/ TBARS Index in patients with type 2 diabetes: a 6-month follow-up randomized controlled study

Acronym

EVID T2DM

Study hypothesis

Six-month vitamin D supplementation will improve insulin resistance, atherogenic risk index and oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin and lifestyle advice.

Ethics approval

Approved 10/04/2019, Ethical Committee of Primary Health Care Center in Podgorica (Trg Nikole Kovačevića 6, Podgorica, Montenegro; Tel: +382 (0)20481900; Email: domzdravljapdg@t-com.me), ID number 05/01-E.K.-5989/1

Study design

Prospective randomized controlled open-label study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Type 2 diabetes mellitus

Intervention

The eligible participants recruited consecutively were randomly assigned to two groups in 1:1 ratio. The serum level of 25(OH)D (marker of vitamin D status) was measured at baseline in all participants. Half of the patients (n=65) were randomly prescribed vitamin D3 therapy and continued their prescribed metformin therapy for 6 months, while the other group (n=65) continued their prescribed metformin therapy only. The dosing was carried out according to the Endocrine Society's clinical practice guidelines as for the vitamin D baseline levels. The participants in the first group who were vitamin D deficient [defined as serum levels of 25(OH)D ≤ 50 nmol/L] were asked to take 50 000 IU of vitamin D3 weekly (equal to 15 drops of vitamin D supplement-Vigantol oil daily) during the first 3 months and 14 000 IU weekly (4 drops daily) for the next 3 months. The participants in the same group whose 25(OH)D levels were > 50 nmol/L were asked to take 14 000 IU weekly (4 drops daily) until the end of the study.

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

1. Glycemic control measured through assessing blood levels of glycated hemoglobin (HbA1c) immunoturbidimetrically at baseline, 3 months and 6 months.
2. Insulin resistance measured using levels of HOMA-IR (the homeostasis model assessment of insulin resistance calculated by the formula: HOMA−IR=Fasting Blood Glucose (mmol/L)×Fasting Insulin (μIU/L)/22.5) at baseline, 3 months and 6 months

Secondary outcome measures

1. Atherogenic risk index is determined through the total cholesterol/HDL cholesterol ratio (Castelli risk I) at baseline, 3 months and 6 months
2. Oxidative stress is measured in plasma through markers of:
2.1. Lipid peroxidation measured in plasma and expressed as the Thiobarbituric acid-reactive substances (TBARS) biomarker malondyadehide (MDA) at baseline, 3 months and 6 months
2.2. Advanced oxidation protein product level (AOPP) measured in plasma spectrophotometrically, expressed as chloramine-T equivalents at baseline, 3 months and 6 months

Overall trial start date

02/04/2018

Overall trial end date

15/12/2018

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Diabetes mellitus type 2
2. ≥ 30 years of age
3. Good metabolic control (HbA1c ≤ 7 %)
4. Treated with metformin and lifestyle advice

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

130 participants

Participant exclusion criteria

1. Use of vitamin D supplements and any diabetes pharmacotherapy other than metformin
2. Use of drugs which affect the metabolism of vitamin D (corticosteroids and anticonvulsants)
3. Severe anemia
4. Chronic liver or kidney failure
5. Alcoholism
6. Pregnancy
7. Malabsorption
8. Urolithiasis
9. Hypercalcemia
10. Body mass index (BMI) ≥ 40 kg/m2
11. Presence of acute or chronic inflammatory conditions

Recruitment start date

03/05/2018

Recruitment end date

31/05/2018

Locations

Countries of recruitment

Montenegro

Trial participating centre

Primary Health Center Podgorica
trg Nikole Kovacevica 6
Podgorica
81000
Montenegro

Sponsor information

Organisation

Primary Health Care Center Podgorica

Sponsor details

Trg Nikole Kovačevića 6
Podgorica
-
Montenegro
+382 (0)20481900
domzdravljapdg@t-com.me

Sponsor type

Hospital/treatment centre

Website

http://www.dzpg.me/

Funders

Funder type

Other

Funder name

Investigator initiated and funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The preparation and submission for publication of manuscripts containing the study results shall be in accordance with a process determined by mutual agreement among the participating institutions.
Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication.

Intention to publish date

15/01/2020

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

02/12/2019: Trial's existence confirmed by Ethical Committee of Primary Health Care Center Podgorica.