Impaired fasting glycaemia MedDRA version: 18.0 Level: LLT Classification code 10046242 Term: Unspecified vitamin D deficiency System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 18.0 Level: PT Classification code 10056997 Term: Impaired fasting glucose System Organ Class: 10027433 - Metabolism and nutriti
Conditions
Interventions
Trade Name: Fultium-D3 3,200 IU capsule
Product Name: Fultium D3 3,200IU (Colecalciferol)
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Coleca
Sponsors
Portsmouth Hospitals NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Individual with a diagnosis of impaired fasting glucose (fasting glucose 6.1-6.9 mmol/l as per WHO criteria) • Age 18 to 75 years inclusive • Participant is willing and able to give informed consent for participation in the study Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: • Established cardiovascular disease (ischaemic heart disease, cerebrovascular disease and peripheral vascular disease) • Individuals with chronic kidney disease (stage 3B- eGFR 30-44 ml/min/1.73 m2 , stage 4- eGFR 15-29 ml/min/1.73 m2 and stage 5- eGFR <15 ml/min/1.73 m2) • Individuals with fat malabsorption- cystic fibrosis, celiac disease, Crohn’s disease, acute or chronic pancreatitis (risk of malabsorption of Vitamin D) • Steroids therapy (increases Vitamin D metabolism and elimination) • On medications that can increase metabolism of vitamin D (phenytoin, phenobarbital, carbamazepine, ketoconazole, rifampicin, non-nucleoside reverse transcriptase inhibitors used in HIV) • Primary hyperparathyroidism • Active granulomatous diseases including sarcoidosis and tuberculosis (increased activity of 1 alfa hydroxylase within granulomas can potentially lead to increased vitamin D toxicity) • Allergy to vitamin D preparations, nitrates (GTN), beta2 agonists (salbutamol) • Already taking vitamin D or calcium supplements • On thiazide diuretics (can reduce renal excretion of calcium and increase risk of hypercalcaemia) • On cardiac glycosides (hypercalcaemia can potentiate cardiac glycosides toxicity) • On metformin • Renal stones • Peanut and soya allergy • Pregnant and intention of becoming pregnant • Breastfeeding • Unable to give consent • Participation in other clinical trials
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to examine whether Vitamin D3 3,200 IU supplementation in patients with impaired fasting glucose has an effect on: Reduction of the VCAM-1 marker (vascular circulating adhesion molecule-1) in blood. VCAM-1 molecule is released to blood circulation when endothelium of the blood vessels is activated by harmful chemicals (oxidative stress and inflammation). ; Secondary Objective: The secondary objective is to examine whether Vitamin D3 3,200 IU supplementation in patients with impaired fasting glucose has positive effect on: 1. Reducing the levels of inflammation markers in the circulation 2. Improvement of body's ability to use insulin more efficiently (insulin sensitivity) 3. Reducing the production of harmful chemicals that damage the body (oxidative stress) 4. Improvement of levels of blood fats (cholesterol, triglycerides) and HbA1c We also aim to examine in sub-analysis whether there are any differences in the above parameters in vitamin D deficient and Vitamin D sufficient participants and to examine the associations between insulin resistance, endothelial function, oxidative stress and vascular inflammation at baseline and after intervention. ;Primary end point(s): Primary outcome measure of the study is the relative change (=Absolute change on logarithmic scale) in VCAM-1 (marker of endothelial activation) folowing administration of Vitamin D3 versus placebo.;Timepoint(s) of evaluation of this end point: VCAM-1 marker will be measured in blood at participant's first study visit. Participants will then take 3,200IU of Colecalciferol daily for 12 weeks (84 days). Following this intervention participants will return for their final visit and a blood test for VCAM-1 marker will be repeated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end points are: • Change in insulin sensitivity (HOMA-B method) • Change in markers of oxidative stress (TAOS, LHP, 8-iso-Prostaglandin F2a Activity, cGMP, GSH/GSSG) • Change in markers of vascular inflammation (hsCRP and ACR) • Change in reflection index of the digital volume waveform after inhalation of salbutamol using finger photoplethysmography • Change in metabolic markers (total cholesterol, LDL and HDL cholesterol, triglycerides, HbA1c) ; Timepoint(s) of evaluation of this end point: At first study visit a blood sample is taken from intravenous line for: 0 min – glucose, insulin, lipids, 25(OH)D3, HbA1c 5 min – glucose and insulin only 10 min – glucose and insulin plus VCAM-1, LHP, cGMP, GSH/GSSG/, TAOS, hsCRP, 8-iso- Prostaglandin F2a Activity From 3 insulin and glucose values (taken 5 minutes apart) insulin sensitivity is calculated using HOMA-B method. Following blood sampling participants undergo painless measurement of endothelium dependent vasodilatation using finger photoplethysmography. Urine sample is taken for ACR. Following their first study visit participants will take 3,200IU of Colecalciferol daily for 12 weeks (84 days). Following this intervention participants will return for their final study visit and all the above tests vill be repeated. | — |
Countries
United Kingdom
Contacts
Public ContactChristine Bevan
Portsmouth Hospitals NHS Trust
Outcome results
None listed