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Vitamin D Supplementation in Children With Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT03417947
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : April 4, 2019
Sponsor:
Collaborator:
Euro-Pharm
Information provided by (Responsible Party):
Genevieve Mailhot, St. Justine's Hospital

Brief Summary:
Sickle cell disease (SCD) is a genetic disease characterized by abnormal hemoglobin, the main constituent of red blood cells. People with SCD have nutritional deficiencies, and vitamin D deficiency is one of the most common. Symptoms of vitamin D deficiency are similar to those of SCD and include chronic pain and bone complications. Correcting vitamin D nutrition of children with SCD represents a treatment that will improve their health. A single oral high-dose of vitamin D3 will be given to SCD children during one of their follow-up visits at the SCD clinic of CHU Sainte-Justine, Montreal, Canada. This mode of administration was chosen to ensure a better adherence to the treatment. The investigators will determine whether this dose is safe and its administration feasible in clinic. The impact of this dose on blood vitamin D and calcium, urinary calcium, growth, inflammation, bone health, pain and quality of life will also be assessed. This study intends to propose a new intervention to improve the nutrition of children with this disease.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Dietary Supplement: Vitamin D bolus Dietary Supplement: Placebo Phase 3

Detailed Description:
Vitamin D deficiency is one of the most common nutritional conditions among patients with sickle cell disease (SCD). Since vitamin D deficiency and SCD share common manifestations including chronic pain, poor bone health and chronic systemic inflammation, it is reasonable to postulate that vitamin D deficiency may contribute to these complications. Thus, optimizing vitamin D nutrition represents an inexpensive strategy that may improve vitamin D status and health outcomes in SCD children. The working hypothesis is that administration of a single oral bolus of 300,000 IU of vitamin D3 to SCD children will result in the attainment of vitamin D sufficiency (25OHD levels >75 nmol/L) in 80% of participants after 3 months. The primary objectives are to assess feasibility, acceptability, and safety of the vitamin D3 bolus while secondary objectives are related to the mean change in serum 25OHD from baseline to 3 months post-bolus and its clinical impact. Seventy-two SCD children (5-17 years, SS and SC genotypes) will be randomized to one bolus of 300,000 IU of vitamin D3 or identical placebo. Blood will be collected at baseline and 3-month post-bolus to measure serum 25OHD and calculate the change from baseline at 3 months (efficacy outcomes). Other outcomes include urinary calcium/creatinine ratio and serum calcium (safety), questionnaires (acceptability and musculoskeletal pain) and parameters related to growth, haematology, inflammation and bone health (exploratory outcomes).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a randomised, quadruble-blind, placebo-controlled, parallel-group trial of vitamin D3 bolus supplementation.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The Applied Clinical Research Unit of Sainte-Justine UHC will generate the randomisation scheme. Group allocation codes will be held in a secure location with a restricted access by the Central pharmacy (Sainte-Justine UHC). All participants and research personnel, including the nurse, research trainee and research team will be blinded to group assignment.

The supplier Euro-Pharm will provide the placebo and vitamin D3 preparations in coded bottles. Pharmacy will prepare the 6-mL bolus in coded syringes following the randomisation scheme.

Primary Purpose: Other
Official Title: Vitamin D Intervention in Children With Sickle Cell Disease: A Pilot Randomized Controlled Trial
Actual Study Start Date : November 30, 2018
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : October 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin D

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo identical to the vitamin D bolus in taste and appearance. The placebo will be administered once, at the beginning of the study. The oral liquid placebo will be prepared at the Pharmacy in coded syringes and will be administered to the participants by a nurse at the sickle cell disease Clinic.
Dietary Supplement: Placebo
Placebo identical in taste and appearance to the vitamin D bolus

Experimental: Vitamin D bolus
The vitamin D bolus is an oral liquid supplement that will be administered once, at the beginning of the study. The oral liquid vitamin D bolus will be prepared at the Pharmacy in coded syringes and will be administered to the participants by a nurse at the sickle cell disease Clinic.The dose of vitamin D3 contained in the bolus is 300 000 IU.
Dietary Supplement: Vitamin D bolus
One single oral liquid vitamin D3 supplement of 300 000 IU
Other Name: Cholecalciferol




Primary Outcome Measures :
  1. Mean change in total serum 25-hydroxyvitamin D levels [ Time Frame: 3 months ]
    Group difference in the mean change in total serum 25OHD from baseline to 3 months.


Secondary Outcome Measures :
  1. Vitamin D sufficiency [ Time Frame: 3 months ]
    Difference in the proportion of children with serum 25-hydroxyvitamin D ≥75nmol/L at 3 months


Other Outcome Measures:
  1. Hypercalciuria [ Time Frame: 7 days post-intervention ]
    Number of patients with urinary calcium to creatinine ratio above normal reference range for age

  2. Hypercalcemia [ Time Frame: 3 months ]
    Number of patients with serum calcium above normal reference range for age

  3. Serum 25-hydroxyvitamin D levels [ Time Frame: 3 months ]
    Number of patients with serum 25-hydroxyvitamin D levels >250 nmol/L

  4. Mean change in weight [ Time Frame: 3 months ]
    Group difference in the mean change of weight (kg) from baseline to 3 months.

  5. Mean change in height [ Time Frame: 3 months ]
    Group difference in the mean change of height (kg) from baseline to 3 months.

  6. Mean change in hemoglobin [ Time Frame: 3 months ]
    Group difference in the mean change of circulating hemoglobin from baseline to 3 months.

  7. Mean change in fetal hemoglobin [ Time Frame: 3 months ]
    Group difference in the mean change of circulating fetal hemoglobin from baseline to 3 months.

  8. Mean change in leucocyte counts [ Time Frame: 3 months ]
    Group difference in the mean change of blood leucocyte counts from baseline to 3 months.

  9. Mean change in platelet counts [ Time Frame: 3 months ]
    Group difference in the mean change of blood platelet counts from baseline to 3 months.

  10. Mean change in reticulocyte counts [ Time Frame: 3 months ]
    Group difference in the mean change of blood reticulocyte counts from baseline to 3 months

  11. Mean change in neutrophil counts [ Time Frame: 3 months ]
    Group difference in the mean change of blood neutrophil counts from baseline to 3 months

  12. Mean change in mean corpuscular volume [ Time Frame: 3 months ]
    Group difference in the mean change of blood mean corpuscular volume from baseline to 3 months

  13. Mean change in serum creatinine [ Time Frame: 3 months ]
    Group difference in the mean change of serum creatinine from baseline to 3 months.

  14. Mean change in serum bilirubin [ Time Frame: 3 months ]
    Group difference in mean change of serum bilirubin from baseline to 3 months.

  15. Mean change in serum parathyroid hormone [ Time Frame: 3 months ]
    Group difference in mean change of serum parathyroid hormone from baseline to 3 months

  16. Mean change in serum P1NP [ Time Frame: 3 months ]
    Group difference in mean change of serum amino-terminal propeptide of type I collagen (P1NP) from baseline to 3 months

  17. Mean change in serum C-telopeptides [ Time Frame: 3 months ]
    Group difference in mean change of serum C-telopeptides from baseline to 3 months

  18. Mean change in musculoskeletal pain scores [ Time Frame: 3 months ]
    Musculoskeletal pain will be assessed with the Brief Pain Inventory (BPI). Group difference in the mean change in BPI scores.

  19. Mean change in quality of life scores [ Time Frame: 3 months ]
    Health-related quality of life will be assessed through the Pediatric Quality of life (PedQoL) inventory. Group difference in the mean change in PedQoL scores.

  20. Sickle cell disease-related complications [ Time Frame: 3 months ]
    Occurrence of sickle cell disease complications affecting bone, the kidneys, the retina, blood vessels, the heart, the lungs, the spleen, the liver and gallbladder during the study period

  21. Participant recruitment [ Time Frame: 3 months ]
    Percentage of patients recruited from those screened

  22. Participant retention [ Time Frame: 3 months ]
    Percentage of patients retained for the entire study duration

  23. Participant compliance [ Time Frame: 3 months ]
    Percentage of patients who comply with the study protocol



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children aged between 5 and 17 years old who are followed up at the SCD Clinic, CHU Sainte-Justine, Montreal, Canada.

Exclusion Criteria:

  • Conditions or use of medications known to interfere with calcium or vitamin D absorption or metabolism
  • Known hypercalcemia
  • Conditions characterized by a hypersensitivity to vitamin D (e.g. granulomatous disorders)
  • Patients clinically diagnosed with rickets or other conditions requiring vitamin D therapy
  • History or presence of urolithiasis
  • Anticipated difficult follow up
  • Patients already enrolled in other investigational studies
  • Patients who have recently been hospitalized for severe pain crisis or acute sickle complication in the past 2 weeks
  • Patients with unresolved pain issues

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): NCT03417947


Contacts
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Contact: Genevieve Mailhot, PhD 514-345-4931 ext 6200 genevieve.mailhot@umontreal.ca
Contact: Nathalie Alos, MD 514-345-4931 ext 2993 nathalie.alos@umontreal.ca

Locations
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Canada, Quebec
CHU Sainte-Justine Recruiting
Montreal, Quebec, Canada, H3T 1C5
Contact: Genevieve Mailhot, PhD    5143454931 ext 6200    genevieve.mailhot@umontreal.ca   
Sponsors and Collaborators
St. Justine's Hospital
Euro-Pharm
Investigators
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Principal Investigator: Genevieve Mailhot, PhD St. Justine's Hospital
  Study Documents (Full-Text)

Documents provided by Genevieve Mailhot, St. Justine's Hospital:
Study Protocol  [PDF] November 30, 2017


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Responsible Party: Genevieve Mailhot, Researcher, St. Justine's Hospital
ClinicalTrials.gov Identifier: NCT03417947     History of Changes
Other Study ID Numbers: ND
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: April 4, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Genevieve Mailhot, St. Justine's Hospital:
Bolus supplementation
Pilot randomised controlled trial
Vitamin D

Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents