Aplastic Anemia, Blood Disorder, Myelodysplastic Syndromes, Pediatric Acute Lymphoid Leukemia, Pediatric Acute Myeloid Leukemia, Pediatric Cancer, Sickle Cell Anemia in Children, Stem Cell Transplant Complications, Thalassemia in Children, Vitamin D Deficiency
Conditions
Brief summary
Research has suggested that children with sufficient vitamin D levels undergoing hematopoietic stem cell transplant (HSCT) have improved outcomes, including lower incidences of infection and graft-versus-host disease (GVHD), as well as overall improved survival. However, supplementation in children undergoing HSCT has shown to be a challenge using standard or aggressive supplementation strategies. The primary objective of this study is to determine the safety and efficacy of a single, high dose oral vitamin D (Stoss Therapy) at the start of transplant followed by maintenance supplementation in children undergoing HSCT.
Detailed description
Comorbidities and complications including infection, organ system toxicity, graft-versus-host disease (GVHD) and disease recurrence are some of the biggest contributors to quality of life and mortality in children undergoing hematopoietic stem cell transplant (HSCT). Research has suggested that patients with sufficient vitamin D levels during transplant have improved outcomes, including lower incidences of infection and acute GVHD, as well as overall improved survival. Prior research has shown that chronically ill children are at risk for vitamin D deficiency, including those undergoing HSCT. Data has shown populations with as many as 70% of HSCT patients have insufficient levels of vitamin D at time of transplant. While several studies have attempted methods of vitamin D supplementation in this subset of patients, there has not been success with either standard or aggressive supplementation strategies. Single high-dose oral vitamin D therapy, known as stoss therapy, has been used in other chronically ill children where adequate levels of vitamin D are difficult to attain. Stoss therapy suggests a single high-dose followed by maintenance dosing would be adequate to replete and maintain vitamin D levels in chronically ill children. While it has been shown to be effective with no evidence of toxicity in patients with rickets and cystic fibrosis, its safety and efficacy has not been studied in the transplant setting. However, there is an urgent need to identify a modifiable factor may reduce the occurrence and/or severity of HSCT associated complications. The overall objective of this study is to determine the effectiveness of a single, high dose oral vitamin D (Stoss Therapy) followed by maintenance supplementation in children undergoing HSCT. This change will result in a new and innovative approach to maintaining adequate vitamin D levels during pediatric HSCT, with the long term goal of reducing morbidity and mortality. Our primary goal is to assess the safety and efficacy of a single, high dose of vitamin D followed by maintenance supplementation in children undergoing HSCT. Our secondary goal is to identify the effects of adequate vitamin D levels on early clinical outcomes such as cytokine levels, graft versus host disease, immune recovery, rejection, relapse, infection rates in pediatric HSCT patients.
Interventions
DIETARY_SUPPLEMENTVitamin D3
The single, oral dose of vitamin D3 is based on patient's age and baseline 25-hydroxy-vitamin D level. Dosing is as follows: (1) For children under 3 years of age. 200000IU for those deficient, 150000IU for those insufficient, and 100000IU for those sufficient; (2) For children 3-12 years of age, 400000IU for those deficient, 350000IU for those insufficient, and 200000IU for those sufficient; (3) For children greater than 12 years of age, 600000IU for those deficient, 500000IU for those insufficient, and 300000IU for those sufficient. This is a single, one time oral dose given prior to the start of transplant.
DIETARY_SUPPLEMENTStandard Vitamin D3 Supplementation
Those who have sufficient vitamin D will be supplemented with 400-600IU/day of Vitamin D3 orally. Those who have insufficient or are deficient in vitamin D will be supplemented with 50,000IU/week of Vitamin D3 orally.
Sponsors
Phoenix Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients enrolled in the study will be randomized to either a control or intervention arm prior to the start of transplant using block randomization of blocks of 6. Those randomized to the intervention arm will receive the intervention (Stoss Therapy dosing of vitamin D) at the start of transplant followed by maintenance supplementation of vitamin D according to standard of care. Those randomized into the control arm will receive only maintenance supplementation of vitamin D according to standard of care throughout transplant.
Eligibility
Sex/Gender
ALL
Age
1 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* All pediatric patients, ages 1 to 25 years of age, undergoing hematopoietic stem cell transplant at Phoenix Children's hospital * Patients must sign an informed consent
Exclusion criteria
* Prior rejection of hematopoietic stem cell transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Stoss Therapy | 100 days | In order to monitor the safety of stoss therapy, patients will be monitored for any clinical signs or symptoms of hypervitaminosis D, including abdominal pain, dehydration, and fatigue. Patients will be monitored for hypercalcemia and hyperphosphatemia with weekly complete metabolic panels and serum phosphorus during the first 100 days of transplant. Patients will have repeat measurements of serum 25(OH)D levels will be obtained at Day +30 to ensure they do not have hypervitaminosis D at that time. |
| Efficacy of vitamin D repletion | 100 days | All patients will have baseline serum 25(OH)D levels obtained prior to transplant. At baseline, patient will be classified as being sufficient (\>30ng/mL), insufficient (21- 29ng/mL), or deficient (\<20ng/mL) in serum vitamin D. All patients will then undergo treatment based on their trial arm and baseline levels of vitamin D. Patients will have repeat measurements of serum 25(OH)D levels will be obtained at Day +100 of transplant. At this time they will again be classified as being sufficient (\>30ng/mL), insufficient (21- 29ng/mL), or deficient (\<20ng/mL) in serum vitamin D following therapy to assess if the therapy was efficacious in repleting and maintaining their serum vitamin D level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rejection | 100 days | All incidences of rejection will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 |
| Relapse | 100 days | All incidences of relapse will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 |
| Graft-versus-host disease | 100 days | All incidences of GVHD will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 |
| Mortality | 100 days | All incidences of mortality will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 |
| Infection Rates | 100 days | All incidences of infection will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100 |
| Immune Recovery | 100 days | Immune recovery will be obtained at Day +100 as per standard of care and recorded in the medical record |
Countries
United States
Outcome results
None listed