A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT

November 13, 2020 updated by: Jessie Bodea, MD, Phoenix Children's Hospital

A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 (Stoss Therapy) in Pediatric Patients Undergoing HSCT to Prevent Vitamin D Deficiency and Insufficiency During Transplant

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single, high dose oral vitamin D3
Patients will take a single oral dose of vitamin D3 based on age and initial vitamin D level. A patient will be classified as sufficient, insufficient, or deficient at the start of therapy. Following this dose, patients will also be given standard vitamin D3 supplementation according to current Endocrine Society Guidelines.
Dietary supplement: Vitamin 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 supplement: Standard 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.
Active Comparator: Standard Vitamin D Supplementation
Patients will be given standard vitamin D3 supplementation during transplant in accordance with standard of care per Endocrine Society Guidelines. This supplementation is based on a patient's initial vitamin D level.
Dietary supplement: Standard 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of Stoss Therapy
Time Frame: 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.
100 days
Efficacy of vitamin D repletion
Time Frame: 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.
100 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Graft-versus-host disease
Time Frame: 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
100 days
Immune Recovery
Time Frame: 100 days
Immune recovery will be obtained at Day +100 as per standard of care and recorded in the medical record
100 days
Rejection
Time Frame: 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
100 days
Relapse
Time Frame: 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
100 days
Infection Rates
Time Frame: 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
100 days
Mortality
Time Frame: 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
100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Phoenix Children's Hospital

Investigators

  • Study Chair: Kayla Burgett, Phoenix Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2017

Primary Completion (Actual)

July 1, 2019

Study Completion (Actual)

July 1, 2019

Study Registration Dates

First Submitted

May 26, 2017

First Submitted That Met QC Criteria

June 1, 2017

First Posted (Actual)

June 6, 2017

Study Record Updates

Last Update Posted (Actual)

November 17, 2020

Last Update Submitted That Met QC Criteria

November 13, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-076

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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