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Vitamin D, Chronic Kidney Disease (CKD) and the Microcirculation

This study has been completed.
Sponsor:
Information provided by:
Barts & The London NHS Trust
ClinicalTrials.gov Identifier:
NCT00882401
First received: April 15, 2009
Last updated: March 21, 2011
Last verified: March 2011
History of Changes
  Purpose

Overall research aims: This study will examine the effect of vitamin D supplementation on the function of the endothelium and microcirculation of patients with chronic kidney disease and vitamin D deficiency.

Hypothesis: Vitamin D therapy in patients with CKD and concomitant vitamin D deficiency will improve endothelial, and therefore microcirculatory function, reduce levels of oxidative stress and thus reduce the risk of future CVS events in this population.


Condition Intervention Phase
Chronic Kidney Disease
Vitamin D Deficiency
 Drug: Ergocalciferol (Vitamin D)
Drug: Placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Vitamin D on the Microcirculation of Patients With Chronic Kidney Disease (CKD) and Vitamin D Deficiency

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Barts & The London NHS Trust:

Primary Outcome Measures:
  • Microcirculatory function - iontophoresis [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Key clinical parameters of CKD management [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: April 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ergocalciferol (oral)
ergocalciferol: 50,000 IU per week for 1 month followed by 50,000 IU per month for 5 months.
 Drug: Ergocalciferol (Vitamin D)
ergocalciferol: 50,000 IU per week for 1 month followed by 50,000 IU per month for 5 months.
Other Name: Drisdol
Placebo Comparator: Placebo
Matching placebo at same dose schedule as ergocalciferol
 Drug: Placebo
Matching placebo at same dose schedule as ergocalciferol

Detailed Description:

Research rationale: Cardiovascular (CVS) diseases are the major cause of death in patients with chronic kidney disease (CKD), accounting for approximately half of all deaths. Patients with CKD are far more likely to die of CVS disease than progress to end stage renal disease. Recently, vitamin D deficiency has been identified as a non-traditional CVS risk factor. However, vitamin D is not routinely prescribed in the early stages of CKD.

Previous publications have established that endothelial, and therefore, microcirculatory dysfunction is a marker of CVS health and a predictor of future CVS events. Studies have also shown that clinical assessments of the microcirculation reflect the overall health and function of the endothelium. Vitamin D has been shown to improve endothelial function in diabetic patients with vitamin D deficiency and normal kidney function. However, no study has examined endothelial dysfunction in patients with CKD and vitamin D deficiency.

With the prevalence of CKD and concomitant vitamin D deficiency increasing worldwide, there is a pressing need to examine the effects of vitamin D therapy in the early stages of CKD. This study involves the use of four, non-invasive, detailed assessments of the microcirculation which could be used in a clinical setting to enhance CVS risk profiling. The current study design includes novel clinical and in vitro work examining endothelial function, oxidative stress levels and potential cellular mechanisms by which vitamin D improves endothelial function. Early detection of endothelial dysfunction, before end stage renal disease is reached, will provide a powerful tool for predicting future CVS events and thus provide an opportunity to intervene with therapies, including vitamin D, at an early stage of renal dysfunction.

Study objectives: Primary study objective - to evaluate the effects of vitamin D therapy on endothelial function in patients with CKD and vitamin D deficiency. Secondary study objective: to evaluate the effects of vitamin D therapy on key clinical parameters in patients with CKD and vitamin D deficiency.

Research plan: We will conduct a double blind, randomised control trial comparing oral ergocalciferol to a placebo in adult, non-diabetic patients with CKD stages 3-4 and vitamin D deficiency (defined as < 10ng/ml (<30nmol/L)). Based on power calculations, 40 subjects will be recruited in each arm as well as 15 healthy control subjects. Subjects will be followed for 7 months in total.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. eGFR between 15 and 60 ml/min/1.73m2
  2. Serum 25 (OH) vitamin D levels <30nmol/L
  3. No evidence of diabetes mellitus (fasting blood sugar <7.1, not taking any diabetic medication)
  4. Not receiving haemo or peritoneal dialysis
  5. No dialysis therapy within the last 3 months
  6. Age > 18 years and < 80 years
  7. Patient agrees not use any medications (prescribed or over-the-counter including herbal remedies) judged to be clinically significant by the Principal Investigator during the course of the study.
  8. Able to understand and sign the written Informed Consent Form.
  9. Able and willing to follow the Protocol requirements.

Exclusion Criteria:

  1. Currently receiving oral ergocalciferol at any dose
  2. Received IM ergocalciferol therapy within last 3 months
  3. Receiving renal replacement therapy of any type or having recently received any form of dialysis (within 3 months)
  4. Pacemaker or any other implanted cardiac device
  5. Serum calcium above 2.6 mmol/L at screening
  6. Pregnant or lactating
  7. Known hypersensitivity to ergocalciferol
  8. Patient known to have a condition which predisposes to hypercalcaemia (multiple myeloma, sarcoidosis, other granulomatous disease)
  9. Initial blood pressure of >160/100 mmHg
  10. History of significant liver disease or cirrhosis
  11. Anticipated requirement for dialysis in 6 months
  12. Malabsorption, severe chronic diarrhea, or ileostomy
  13. Known diagnosis of hypervitaminosis D
  14. Known to have diabetes mellitus
  15. Known to have renal calculi
  16. Known to have systemic sclerosis, Raynaud's phenomenon or other disease associated with known microcirculatory dysfunction
  17. Concurrent participation in any other research study
  18. Unwilling or unable to complete study protocol
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00882401

Locations
United Kingdom
Barts and the London NHS Trust
London, United Kingdom, E1 1BB
Sponsors and Collaborators
Barts & The London NHS Trust
Investigators
Study Chair: Magdi Yaqoob, MB ChB Barts and the London NHS Trust
  More Information

No publications provided

Responsible Party: Dr Gavin Dreyer, Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT00882401     History of Changes
Other Study ID Numbers: 2008-008745-38, EUDRACT number 2008-008745-38
Study First Received: April 15, 2009
Last Updated: March 21, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Kidney Diseases
Vitamin D Deficiency
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Urologic Diseases
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
 Renal Insufficiency
Ergocalciferols
Vitamin D
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on May 19, 2013