Prevention of Vitamin D Deficiency Following Pediatric CHD Surgery: a Phase II Dose Evaluation Randomized Controlled Trial Comparing Usual Care With a High Dose Pre-operative Supplementation Regimen Based on the Institute of Medicine Daily Upper Tolerable Intake Level (HICCUPS 2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Children's Hospital of Eastern Ontario
Sponsor:
Collaborators:
The Ottawa Hospital
McGill University
Children's University Hospital, Ireland
Ottawa Hospital Research Institute
Information provided by (Responsible Party):
James Dayre McNally, Children's Hospital of Eastern Ontario
ClinicalTrials.gov Identifier:
NCT01838447
First received: April 11, 2013
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

Our research group has shown that almost all children with congenital heart disease (CHD) are vitamin D deficient following heart surgery. This work strongly suggests that the vitamin D intake presently recommended for healthy children, and also given to children with CHD, is inadequate to prevent vitamin D deficiency following surgery. Unfortunately, there have been no studies investigating any other vitamin D dose in children with heart disease. Recently, a higher dose of vitamin D intake has been approved (by the Institute of Medicine and Health Canada) and recent work on healthy children has shown it to be safe. The objective of this study is to determine whether this recently approved higher dose of vitamin D can safely reduce the number of children who are vitamin D deficient following surgery. This dose evaluation study will also evaluate whether it is possible to perform a large study (across Canada) to determine whether vitamin D supplementation can improve outcomes following surgery. It is hypothesized that a daily high dose vitamin D regimen, modeled on the Institute of Medicine daily upper tolerable intake level (UL), will significantly reduce vitamin D deficiency following CHD surgery, when compared with usual intake.


Condition Intervention Phase
Vitamin D Deficiency
Thoracic Surgery
Pediatric Disorders
Heart Defects, Congenital
Dietary Supplement: Cholecalciferol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prevention of Post-Cardiac Surgery Vitamin D Deficiency in Children With Congenital Heart Disease: A Pilot Dose Evaluation Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Eastern Ontario:

Primary Outcome Measures:
  • Blood 25 hydroxyvitamin D (25OHD) concentrations [ Time Frame: 1 day (On admission to the pediatric intensive care unit (PICU) following CHD surgery) ] [ Designated as safety issue: No ]
    Blood 25OHD will be measured to determine vitamin D deficiency, with a concentration below 50 nmol/L used to define deficiency.


Secondary Outcome Measures:
  • Hypercalcemia as a Vitamin D related adverse event [ Time Frame: Immediately before surgery, on admission to the PICU following CHD surgery, and on post-operative days 1,3,5 & 10 ] [ Designated as safety issue: Yes ]
    Hypercalcemia will be defined as an ionized calcium level above 1.40 mmol/L; or above 1.45 mmol/L for children under 8 weeks. Hypercalcemia will be evaluated in blood collected immediately before CHD surgery and throughout the post-operative course (measurements are standard of care).

  • Hypercalcuria as a vitamin D related adverse event [ Time Frame: Immediately before surgery, on admission to the PICU following CHD surgery, and on the first post-operative day ] [ Designated as safety issue: Yes ]
    Hypercalcuria will be identified using calcium:creatine ratios defined using age-specific norms and thresholds

  • Vitamin D parathyroid renal axis function through changes in blood 1,25-dihydroxycholecalciferol [ Time Frame: Immediately before surgery, on admission to the PICU following CHD surgery, and on post-operative days 1,3,5 & 10 ] [ Designated as safety issue: No ]
    Impaired vitamin D axis function will be defined as an inability to restore and maintain active hormone levels in the normal range following surgery after the first post-operative day

  • Changes in cathelicidin as measure of innate immune function [ Time Frame: Immediately before surgery, on admission to the PICU following CHD surgery, and on post-operative days 1,3,5 & 10 ] [ Designated as safety issue: No ]
  • Post-operative PICU catecholamine requirements [ Time Frame: At any point between PICU admission and discharge, an average length of 5-7 days and not longer than 60 days ] [ Designated as safety issue: No ]
    Primarily, post-operative catecholamine requirements during the PICU admission will be evaluated as a dichotomous variable (yes/no). Secondarily, inotrope requirements will be determine using the inotrope score, evaluated as the maximum score and in a time to event approach (off all inotropes, score of zero)

  • Cardiovascular function through an echocardiogram [ Time Frame: Post-operative day 1 ] [ Designated as safety issue: No ]
    The post-operative day 1 echocardiogram will be used to evaluate for differences in cardiovascular function between study arms.


Estimated Enrollment: 62
Study Start Date: July 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Usual care group
This group will receive daily cholecalciferol (vitamin D3) based on the Adequate Intake (AI) for infants and the Recommended Dietary Allowance (RDA) for children over 1 year. Specific dose amounts are 400 IU per day for infants (0-1 year), and 600 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a placebo solution.
Experimental: High Dose Group
This group will receive cholecalciferol (vitamin D3) based on the age-specific tolerable daily upper intake level (UL). Specific dose amounts are 1600 IU per day for infants (0-1 year), and 2400 IU per day for children between 1-17 years. Infants under 12 months of age who are formula fed will be given a dose of 1200 IU per day to account for vitamin D in formula.
Dietary Supplement: Cholecalciferol
The High Dose group is based on the age-specific UL. These doses were chosen to elevate 25OHD well above 50 nmol/L, while minimizing the risk of vitamin D toxicity (e.g. hypercalcemia, hypercalciuria)
Other Name: Vitamin D3

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   36 Weeks to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Corrected gestational age between 36 weeks gestational age and 18 years
  • Has CHD that will require surgery within the next 12 months
  • CHD requiring surgical intervention with cardiopulmonary bypass

Exclusion Criteria:

  • Born at less than 32 weeks gestational age
  • Corrected gestational age of less than 36 weeks
  • Cardiac or gastrointestinal disease preventing enteral feeds or drug administration prior to surgery
  • Patient has confirmed or suspected Williams syndrome
  • Proposed surgery to take place at another centre (outside of CHEO)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01838447

Contacts
Contact: James D McNally, M.D., Ph.D. 613-737-7600 ext 3553 dmcnally@cheo.on.ca

Locations
Canada, Ontario
Children's Hospital of Eastern Ontario Recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Tara Girolamo, RN, B.Sc.N.    613-737-7600 ext 3639    girolamo@cheo.on.ca   
Contact: Katharine J O'Hearn, M.Sc.    613-737-7600 ext 4006    kohearn@cheo.on.ca   
Principal Investigator: James D McNally, M.D., Ph.D.         
Sub-Investigator: Kusum Menon, M.D.         
Sub-Investigator: Gyaandeo Maharajh, M.D., C.M.         
Sub-Investigator: Margaret Lawson, M.D.         
Sub-Investigator: Osama Y Al-Dirbashi, Ph.D.         
Sub-Investigator: Stephanie Redpath, MD         
Sub-Investigator: Jane Loughead, MD         
Sponsors and Collaborators
Children's Hospital of Eastern Ontario
The Ottawa Hospital
McGill University
Children's University Hospital, Ireland
Ottawa Hospital Research Institute
Investigators
Principal Investigator: James D McNally, M.D., Ph.D. Children's Hospital of Eastern Ontario
Study Chair: Kusum Menon, M.D. Children's Hospital of Eastern Ontario
Study Chair: Lauralyn McIntyre, M.D. Ottawa Hospital
Study Chair: Dermot R Doherty, M.B., B.Ch. Temple Street Children's University Hospital Dublin and University College
Study Chair: Dean Ferguson, Ph.D. Ottawa Hospital Research Institute
Study Chair: Hope Weiler, Ph.D. McGill University
  More Information

Publications:
Bogermann J. 1,25-Dihydroxyvitamin D fluctuations in cardiac surgery are related to age and clinical outcome. Critical Care Medicine 40:2073-2081, 2012.
Schlingmann KP et al. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. The New England Journal of Medicine 365: 410-421, 2011.

Responsible Party: James Dayre McNally, Dr. James Dayre McNally, Pediatric Intensivist, Department of Pediatrics, CHEO, Associate Investigator, CHEO Research Institute, Children's Hospital of Eastern Ontario
ClinicalTrials.gov Identifier: NCT01838447     History of Changes
Other Study ID Numbers: VITAMINDINCHD-01
Study First Received: April 11, 2013
Last Updated: July 15, 2013
Health Authority: Canada: Health Canada

Keywords provided by Children's Hospital of Eastern Ontario:
Vitamin D
Congenital Heart Disease
Cardiac Surgery
Pediatrics
Phase II Clinical Trial

Additional relevant MeSH terms:
Heart Defects, Congenital
Congenital Abnormalities
Heart Diseases
Vitamin D Deficiency
Cardiovascular Abnormalities
Cardiovascular Diseases
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on July 22, 2014