Atherosclerosis, Chronic Kidney Disease
Conditions
Keywords
Vitamin D, Cholecalciferol, Chronic Kidney Disease, Cardiovascular Disease, Atherosclerosis, Flow Mediated Dilatation, Carotid Intima Media Thickness, CD4+CD28null T lymphocyte, Regulatory T lymphocyte
Brief summary
A pilot study to assess feasibility of methods of an observer-blinded randomised controlled trial of the effect of vitamin D supplementation in Chronic Kidney Disease and low vitamin D levels on markers of vascular function (Flow Mediated Dilatation of Brachial Artery), vascular structure (Carotid Intima Media Thickness) and Immune Regulation (frequencies of CD4+CD28null T lymphocytes ad Regulatory T lymphocytes).
Detailed description
The study is a single (observer) blinded feasibility pilot randomised study. Study subjects will be recruited from clinics run by St George's Hospital Renal Department and randomised to treatment arm or no treatment arm. In treatment arm, six doses of vitamin D tablets (cholecalciferol 100,000 IU, five capsules total) will be administered on weeks 0, 4, 8, 12, 16 and 20. In the no-treatment arm the participants receive no cholecalciferol. Participants will have serum calcium levels measured at week 12. All participants will undergo estimation of endothelial function, carotid intima-media thickness, CD4+CD28null and regulatory T cell frequency in week 0 and week 26. The observer will be blinded to whether the patient is in the treatment or no-treatment arm whilst the following tests are performed: 1. Measurement of Brachial Artery Flow Mediated Dilatation 2. Measurement of Carotid Intima Media Thickness 3. Quantification of CD4+CD28null and regulatory T cell frequency The pilot study will assess feasibility of the study methods.
Interventions
DIETARY_SUPPLEMENTVitamin D (cholecalciferol)
(aviticol) 5x 20,000unit capsules administered monthly over 20 weeks
Sponsors
St George's, University of London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80 years 2. Calcium \< 2.58mmol/l 3. On an ACE inhibitor/ARB 4. Vitamin D \<75nmol/l 5. eGFR 15- 60ml/min/1.73m2 and stable 6. Informed consent to participate
Exclusion criteria
1. Patients already on Vitamin D or calcium supplementation 2. Patients with known malignancies 3. Patients with autoimmune conditions 4. Patients with heart failure (ejection fraction \<40%, Plasma NT pro-BNP\>500pg/ml) 5. Patients with active infection 6. Rapidly deteriorating renal function 7. Recent Acute coronary syndrome or cerebro-vascular event (within the last 6 months) 8. Uncontrolled hypertension (BP\>160 systolic)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adherence to vitamin D supplementation | 6 months | Subjective adherence as assessed by Participant Experience Survey and biochemical correlation by comparison of follow up vitamin D levels |
| Acceptability to patients of randomisation procedures | 6 months | Acceptability as assessed by quantitative and qualitative analysis of Participant Experience Survey |
| Randomisation procedure | 6 months | Comparison of baseline indices of two patient groups |
| Maintenance of single (observer) blinding | 6 months | Incidences of unblinding of study investigator |
| Recruitment rate | 3 months | Percentage of patients recruited from those eligible for the study. |
| Retention rate | 6 months | Percentage of patients recruited who completed the follow up investigations |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Witnessed change in CIMT between treated and untreated subjects | 6 months | Carotid Intima Media Thickness |
| Witnessed change in T lymphocyte subset frequency between treated and untreated subjects | 6 months | CD4+CD28null T lymphocytes and Regulatory T cells as determined by flow cytometry of whole blood |
| Witnessed change in FMD between treated and untreated subjects | 6 months | Flow Mediated Dilatation |
Countries
United Kingdom
Outcome results
None listed