Vitamin D Supplementation in CKD - Vascular Function, Structure and Immune Regulation

Impact of Vitamin D Supplementation on Vascular Function, Vascular Structure and Immune Regulation in Patients With Chronic Kidney Disease and Low Vitamin D Levels - A Pilot Randomised Trial

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).

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Chronic Kidney Disease
• Intervention / Treatment: Dietary supplement: Vitamin D (cholecalciferol)

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Tooting
    • London, Tooting, United Kingdom, sw17 0QT
      • Debasish Banerjee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D Group; Six doses of cholecalciferol 100,000units (5x aviticol 20,000units capsules) administered monthly over 20 weeks.	Dietary supplement: Vitamin D (cholecalciferol); (aviticol) 5x 20,000unit capsules administered monthly over 20 weeks
No Intervention: Control; No vitamin D given

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	Percentage of patients recruited from those eligible for the study.	3 months
Retention rate	Percentage of patients recruited who completed the follow up investigations	6 months
Acceptability to patients of randomisation procedures	Acceptability as assessed by quantitative and qualitative analysis of Participant Experience Survey	6 months
Randomisation procedure	Comparison of baseline indices of two patient groups	6 months
Maintenance of single (observer) blinding	Incidences of unblinding of study investigator	6 months
Adherence to vitamin D supplementation	Subjective adherence as assessed by Participant Experience Survey and biochemical correlation by comparison of follow up vitamin D levels	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Witnessed change in FMD between treated and untreated subjects	Flow Mediated Dilatation	6 months
Witnessed change in CIMT between treated and untreated subjects	Carotid Intima Media Thickness	6 months
Witnessed change in T lymphocyte subset frequency between treated and untreated subjects	CD4+CD28null T lymphocytes and Regulatory T cells as determined by flow cytometry of whole blood	6 months

Collaborators and Investigators

• Sponsor: St George's, University of London
• Investigators: Principal Investigator: Debasish Banarjee, St Georges University NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: July 19, 2016
• First Submitted That Met QC Criteria: May 7, 2020
• First Posted (Actual): May 8, 2020

Study Record Updates

• Last Update Posted (Actual): May 8, 2020
• Last Update Submitted That Met QC Criteria: May 7, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Vitamin D; Cardiovascular Disease; Atherosclerosis; Chronic Kidney Disease; Cholecalciferol; Flow Mediated Dilatation; Carotid Intima Media Thickness; CD4+CD28null T lymphocyte; Regulatory T lymphocyte
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Atherosclerosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 15.0236

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED