Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 68 of 356 for:    Recruiting, Not yet recruiting, Available Studies | "nutrition disorders" | Child

Rapid Normalization of Vitamin D Deficiency in PICU (VITdALIZE-KIDS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03742505
Recruitment Status : Recruiting
First Posted : November 15, 2018
Last Update Posted : August 6, 2019
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
EURO-PHARM International Canada, Inc.
Canadian Critical Care Trials Group
Information provided by (Responsible Party):
James Dayre McNally, Children's Hospital of Eastern Ontario

Brief Summary:

Vitamin D plays an important role in calcium balance, heart and lung health, inflammation, infection prevention, and muscle strength. Due to these roles, it has been suggested that critically ill patients with low vitamin D levels might have higher rates of death and worse long-term health. We believe that identifying critically ill children with vitamin D deficiency and then restoring vitamin D levels quickly could represent a safe, easy and inexpensive means of reducing patient illness, preventing death and improving quality of life. This clinical trial will determine whether rapid normalization of vitamin D deficiency improves survival and health-related quality of life following critical illness. The VITdALIZE-KIDS trial is a multicentre randomized clinical trial in Canadian Pediatric Intensive Care Units (PICUs). Critically ill children who agree to participate (consent given by caregivers) will have their blood vitamin D level measured, and those who are vitamin D deficient will be randomized to receive a single dose of either high-dose vitamin D3 or placebo (no drug).

Study participants assigned to the high-dose vitamin D arm will receive 10,000 IU/kg of enteral cholecalciferol (up to a maximum of 400,000 IU). We have tested this dose in a pilot trial, and no patient experienced serious adverse events related to vitamin D administration. Patients will be followed for 90 days to determine whether they survived and had a significant change in their health and quality of life. Vitamin D deficiency is a common problem not only among critically ill Canadian children, but in PICUs worldwide. In addition to being applicable in Canada, our study protocol was designed to be generalizable and meaningful to critically ill children worldwide.


Condition or disease Intervention/treatment Phase
Vitamin D Deficiency Drug: Cholecalciferol Other: Placebo Phase 3

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 766 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Pragmatic, Phase III, multi-centre, double-blinded randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The randomization lists will only be accessible to the Methods Centre at the Ottawa Hospital Research Institute and the research pharmacist(s). The active drug and placebo are identical (e.g. colour, consistency, volume, taste, smell, containers).
Primary Purpose: Treatment
Official Title: Rapid Normalization of Vitamin D Deficiency in PICU: A Multi-Centre Phase III Double-Blind Randomized Controlled Trial
Actual Study Start Date : June 17, 2019
Estimated Primary Completion Date : May 31, 2023
Estimated Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Vitamin D

Approximately half of the subjects randomized into VITdALIZE-KIDS will be randomized into the Vitamin D Group and will receive a single dose of cholecalciferol at enrolment.

Participants may also receive standard vitamin D dosing at the discretion of the care team (e.g. 400-1000 IU/day).

Drug: Cholecalciferol
Single enteral cholecalciferol load at a dose of 10,000 IU/kg (maximum 400,000 IU)

Placebo Comparator: Placebo

Approximately half of the subjects randomized into VITdALIZE-KIDS will be randomized into the Placebo Group and will receive a single dose of placebo at enrolment.

Participants may also receive standard vitamin D dosing at the discretion of the care team (e.g. 400-1000 IU/day).

Other: Placebo
Single enteral placebo dose equivalent in volume to the appropriate weight-based dose of cholecalciferol




Primary Outcome Measures :
  1. Health related quality of life [ Time Frame: 28 days ]
    The primary outcome will be health related quality of life. Health related quality of life will be measures using the age-appropriate PedsQL scale (Ages: 2-7, PedsQL 4.0 Generic Core Scales; Ages 1-24 months: PedsQL™ Infant Core Scales (1-24 months). The PedsQL requires only 23 items to score (36 items for the infant scales), a task easily completed in 5-7 minutes and assesses four domains: physical, emotional, social, and school functioning. The mean PedsQL Core Scale is equal to the sum of all items over the number of items answered on all the Scales and generates a number out of 100. The scoring for the scale is the same for both the PedsQL 4.0 Generic Core Scale and PedsQL Infant Core Scale, allowing the score from either scale to be reported together as one outcome.


Secondary Outcome Measures :
  1. New and/or progressive multiple organ dysfunction [ Time Frame: 28 days ]
    The proportion of patients who develop new or progressive multiple organ dysfunction (NPMODS) will be determined using the updated Pediatric Logistic Organ Dysfunction Score (PELOD-2). For patients with no organ dysfunction at randomization, new multiple organ dysfunction syndrome (MODS) will be defined as the development of ≥2 simultaneous organ dysfunctions during the 28 days following randomization (for patients without organ dysfunction at enrolment) or ≥1 simultaneous organ dysfunction (for patients with at least one existing organ dysfunction at enrolment). Progressive MODS will be defined as development of ≥1 additional simultaneous organ dysfunction in a patient with MODS at enrolment. All deaths will be considered Progressive MODS.


Other Outcome Measures:
  1. Functional status [ Time Frame: 28 and 90 days ]
    Will be measured using the Functional Status Scale (FSS), which was developed specifically for PICU research, has been both validated against the pediatric performance scales (PCPC/POPC) and has had meaningful change established (3 points). The FSS includes 6 functional domains (mental status, sensory function, communication, motor function, feeding, and respiratory status) and uses a 5-point scale to rate infant function from 1 (normal) to 5 (very severe dysfunction); total scores range from 6 (normal) to 30 (very severe dysfunction).

  2. Mortality [ Time Frame: 28 and 90 days ]
    Consistent with most critical care studies we will evaluate mortality alone

  3. PICU length of stay [ Time Frame: Up to 90 days post-randomization ]
    Duration (in hours and days) of PICU length of stay from time of PICU admission and from time of study enrollment

  4. Hospital length of stay [ Time Frame: Up to 90 days post-randomization ]
    Duration (in days) of hospital length of stay from time of admission and from time of study enrollment

  5. Serious adverse events [ Time Frame: Randomization to 90 days post-randomization ]
    We will report on the frequency of expected and unexpected serious adverse events plausibly associated with vitamin D administration.

  6. Vitamin D toxicity [ Time Frame: Randomization to 90 days post-randomization ]
    We will report on the frequency of biochemical and clinical events potentially related to vitamin-D. Biochemical and clinical events possible related to vitamin D administration include hypercalcemia, nephrocalcinosis/renal stones (symptomatic), and gastric perforation/bleeding.

  7. Change in vitamin D status and axis functioning [ Time Frame: Enrolment and on >48 hours following enrollment (range: Day 2-7) ]
    We will evaluate for change in vitamin D status and axis functioning through blood concentrations of the 1,25(OH)2D and 25OHD metabolites.

  8. Metabolomic profiling [ Time Frame: Enrolment and on >48 hours following enrollment (range: Day 2-7) ]
    Non-targeted metabolomics analysis will be performed on blood and urine using an extensively validated multiplexed separation method for high throughput metabolic phenotyping based on muti-segment injection capillary electrophoresis-mass spectrometry10. This method is applicable to the analysis of a wide array of ionic/polar metabolites in volume-limited biological samples with data fidelity, including matching serum and urine specimens.

  9. Biomarker Analysis - C-Reactive Protein [ Time Frame: Enrolment and on >48 hours following enrollment (range: Day 2-7) ]
    In a sub-set of 100 patients (assuming adequate biological sample volume is obtained), we will report on and compare, by group, the baseline and post-intervention levels of multiple biomarkers shown to be vitamin D responsive in other related populations.

  10. Biomarker Analysis - Pro-inflammatory cytokines [ Time Frame: Enrolment and on >48 hours following enrollment (range: Day 2-7) ]
    In a sub-set of 100 patients (assuming adequate biological sample volume is obtained), we will report on and compare, by group, the baseline and post-intervention levels of multiple biomarkers shown to be vitamin D responsive in other related populations.

  11. Biomarker Analysis - Anti-inflammatory cytokines [ Time Frame: Enrolment and on >48 hours following enrollment (range: Day 2-7) ]
    In a sub-set of 100 patients (assuming adequate biological sample volume is obtained), we will report on and compare, by group, the baseline and post-intervention levels of multiple biomarkers shown to be vitamin D responsive in other related populations.

  12. Biomarker Analysis - Brain natriuretic peptide [ Time Frame: Enrolment and on >48 hours following enrollment (range: Day 2-7) ]
    In a sub-set of 100 patients (assuming adequate biological sample volume is obtained), we will report on and compare, by group, the baseline and post-intervention levels of multiple biomarkers shown to be vitamin D responsive in other related populations.

  13. Biomarker Analysis - Cathelicidin [ Time Frame: Enrolment and on >48 hours following enrollment (range: Day 2-7) ]
    In a sub-set of 100 patients (assuming adequate biological sample volume is obtained), we will report on and compare, by group, the baseline and post-intervention levels of multiple biomarkers shown to be vitamin D responsive in other related populations.

  14. Biomarker Analysis - Bone markers [ Time Frame: Enrolment and on >48 hours following enrollment (range: Day 2-7) ]
    In a sub-set of 100 patients (assuming adequate biological sample volume is obtained), we will report on and compare, by group, the baseline and post-intervention levels of multiple biomarkers shown to be vitamin D responsive in other related populations.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Anticipated PICU stay ≥48 hours
  • Corrected gestational age 37 weeks to age 18 years
  • Expected to require clinically indicated blood work >48 hours following study enrollment (Range: 2-7 days)
  • Vitamin D deficiency, as defined by blood 25OHD < 50 nmol/L at the time of screening

Exclusion Criteria:

  • Treating physician refuses enteral drug administration due to gastrointestinal disorder,
  • Persistent hypercalcemia (ionized calcium >1.40 mmol/L (age >2 months), >1.45 (age <2 months) excluding transient abnormalities and those related to parenteral calcium administration for hypocalcemia;
  • Confirmed or suspected William's syndrome;
  • Known nephrolithiasis or nephrocalcinosis;
  • Imminent plan for withdrawal of treatment or transfer to another ICU not participating in the VITdALIZE-KIDS trial;
  • Physician refusal;
  • Previous enrollment in this trial;
  • Granulomatous disease (tuberculosis or sarcoidosis);
  • Severe liver failure;
  • Hypersensitivity or allergy to vitamin D or any of the non-medicinal ingredients of the formulation;
  • Patient on thiazide diuretics also receiving regular ongoing calcium supplementation above the daily recommended intake;
  • Adolescent female of child-bearing age with a positive pregnancy serum test;
  • Patient on digoxin-therapy; and
  • Treating physician intends to administer vitamin D doses above 1000 IU (e.g. patient presents with isolated clinical symptoms of severe VDD, severe burns).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03742505


Contacts
Layout table for location contacts
Contact: Dayre McNally, MD, PhD 613-737-7600 ext 3553 dmcnally@cheo.on.ca
Contact: Katie O'Hearn, MSc 613-737-7600 ext 4006 kohearn@cheo.on.ca

Locations
Layout table for location information
Canada, Alberta
Alberta Children's Hospital Not yet recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Simon Parsons, MD         
Canada, British Columbia
BC Children's Hospital Not yet recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Srinivas Murthy, MD, CM         
Principal Investigator: Srinivas Murthy, MD, CM         
Canada, Nova Scotia
IWK Health Centre Not yet recruiting
Halifax, Nova Scotia, Canada, B3K 6R8
Contact: Kristina Krmpotic, MD         
Principal Investigator: Kristina Krmpotic, MD         
Canada, Ontario
McMaster Children's Hospital Not yet recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: Karen Choong, MB, MSc         
Principal Investigator: Karen Choong, MB, MSc         
Principal Investigator: Philip Britz-McKibbin, PhD         
Division of Critical Care, Department of Pediatrics, Victoria Hospital Not yet recruiting
London, Ontario, Canada, N6C 3T6
Contact: Anna Gunz, MD         
Principal Investigator: Anna Gunz, MD         
Children's Hospital of Eastern Ontario Recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Dayre McNally, MD, PhD         
Principal Investigator: Dayre McNally, MD, PhD         
Sub-Investigator: Kusum Menon, MD, MSc         
Sub-Investigator: Margaret Lawson, MD         
Sub-Investigator: Pavel Geier, MD, PhD         
Canada, Quebec
Montreal Children's Hospital Not yet recruiting
Montreal, Quebec, Canada, H4A 3J1
Contact: Patricia Fontela, MD, PhD         
Principal Investigator: Patricia Fontela, MD, PhD         
Centre hospitalier universitaire Sainte-Justine Not yet recruiting
Montréal, Quebec, Canada, H3T 1C5
Contact: Marisa Tucci, MD, PhD         
Principal Investigator: Philippe Jouvet, MD, PhD         
Sponsors and Collaborators
Children's Hospital of Eastern Ontario
Canadian Institutes of Health Research (CIHR)
EURO-PHARM International Canada, Inc.
Canadian Critical Care Trials Group
Investigators
Layout table for investigator information
Principal Investigator: Dayre McNally, MD, PhD Children's Hospital of Eastern Ontario

Layout table for additonal information
Responsible Party: James Dayre McNally, Pediatric Intensivist, Children's Hospital of Eastern Ontario
ClinicalTrials.gov Identifier: NCT03742505     History of Changes
Other Study ID Numbers: VITdALIZE-KIDS
First Posted: November 15, 2018    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Nutrition Disorders
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents