Impact of Vitamin D Therapy on Thyroid Function and Antibody Levels in Pediatric Graves' Disease

Impact of Vitamin D Therapy on Thyroid Function and Antibody Levels in Pediatric Graves' Disease: A Pilot Feasibility Trial

The goal of this randomized pilot feasibility clinical trial is to determine the feasibility of implementing a protocol for a larger trial to assess the effects of high-dose vitamin D supplementation in pediatric patients (9-17 years old) newly diagnosed with Graves' disease. The main questions it aims to answer are:

What are the recruitment and adherence rates for a larger trial using this protocol? Is the data collection process complete and robust enough for a larger trial? What are the potential barriers to implementing a larger-scale trial? Researchers will compare vitamin D supplementation plus standard methimazole therapy to methimazole therapy alone (with participants permitted to take up to 1000 International Units of vitamin D2 daily) to explore potential effects on thyroid hormone and antibody levels.

Participants will:

Be randomized to either the intervention or control group. Take study medications (vitamin D or placebo) as directed. Attend regular study visits for blood tests and clinical assessments. Complete medication logs.

Study Overview

• Status: Recruiting
• Conditions: Graves Disease; Hyperthyroidism; Graves' Disease
• Intervention / Treatment: Drug: Ergocalciferol 50,000 IU; Drug: Methimazole

Detailed Description

This pilot feasibility study will evaluate the practicality of conducting a larger randomized controlled trial (RCT) investigating the impact of high-dose vitamin D2 (ergocalciferol) supplementation as an adjunctive therapy to standard methimazole treatment in pediatric patients aged 9-17 years newly diagnosed with Graves' disease (GD). This study aims to address the current gap in research regarding vitamin D supplementation's effect on antibody and thyroid hormone trends in this population. Specifically, the study will examine the feasibility of recruitment, adherence to the intervention regimen, completeness of data collection, and any potential barriers to implementing a larger-scale trial.

The rationale for this study stems from the observed association between low vitamin D levels and an increased risk of Graves' disease, coupled with the limited data on vitamin D supplementation's influence on disease progression in children. This pilot study will investigate whether high-dose vitamin D supplementation, alongside methimazole, affects Thyroid Receptor Antibody (TRAb) and Thyroid Stimulating Immunoglobulin (TSI) antibody levels, as well as thyroid hormone levels (Total T3, Free Thyroxine, Total Thyroxine, TSH), in newly diagnosed pediatric GD patients.

Participants will be randomized 1:1 to either an intervention arm (methimazole + high-dose vitamin D2) or a control arm (methimazole only, with the option of taking up to 1000 IU/day of vitamin D2). The intervention arm will receive 50,000 IU of vitamin D2 weekly for 8 weeks, followed by 50,000 IU every two weeks for 16 weeks, along with standard methimazole therapy as directed by their treating endocrinologist. The control arm will receive standard methimazole therapy alone, per their physician's orders, with the option of taking up to 1000 IU of Over-the-counter (OTC) vitamin D2 daily, if desired. The study will not provide this OTC vitamin D.

The primary feasibility outcomes will be: (1) recruitment rate; (2) adherence rate to the vitamin D supplementation, assessed through pill counts, medication logs, and self-report; (3) data completeness; and (4) identification of any barriers encountered during study implementation. Exploratory clinical outcomes will include time to normalization of thyroid function tests and the percentage change from baseline in TRAb and TSI antibody levels at 24 weeks. Safety and tolerability will be closely monitored, with particular attention to hypercalcemia and hypervitaminosis D. Data on adverse events will be collected and graded using the CTCAE v5.0.

Data analysis will primarily focus on descriptive statistics for feasibility outcomes. Exploratory clinical outcomes will be analyzed to estimate effect sizes and variability, informing the design of a future, adequately powered RCT. This pilot study is not powered to detect statistically significant differences in clinical outcomes.

This study will provide critical preliminary data and feasibility metrics to inform the development of a larger, more definitive RCT evaluating vitamin D's efficacy as an adjunctive therapy in pediatric Graves' disease. This research has the potential to significantly advance our understanding of the role of vitamin D in autoimmune thyroid disease and contribute to improved treatment strategies for children with Graves' disease.

The FDA has granted an Investigational New Drug (IND) exemption (PIND 176865, dated April 30, 2025) for this pilot feasibility study evaluating high-dose vitamin D2 in children with Graves' disease. The exemption allows the study to proceed without a full IND application.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sharon Hyman, MD; Phone Number: 15164723750; Email: Shyman1@northwell.edu
• Study Contact Backup: Name: Sofya Ilmer, MD; Phone Number: 5164723750; Email: silmer@northwell.edu

Study Locations

• United States
  • New York
    • New Hyde Park, New York, United States, 11042
      • Recruiting
      • Pediatric Endocrinology at Northwell Health
      • Contact: Sofya Ilmer, MD; Phone Number: 516-472-3750; Email: silmer@northwell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All new pediatric participants aged 9-17 years with a new diagnosis of GD who will be started on methimazole, will be offered to participate at the time of diagnosis.
• Biochemical features include:
• Suppressed TSH <0.1.
• Elevated T3
• Elevated Free T4
• Elevated T4
• Positive TSI or TRAb. The presence of antibodies is diagnostic.
• Our study will offer enrollment to non-English speaking participants

Exclusion Criteria:

• Initial hydroxy vitamin D levels >80 ng/mL
• Hypocalcemia, corrected calcium based on albumin <8.4 mg/dL
• Hypercalcemia, corrected calcium based on albumin >10.5 mg/dL
• Conditions that affect vitamin D metabolism such as: malabsorption, chronic kidney or liver disease, nephrocalcinosis, hyperparathyroidism
• Current use of medications which are known to affect thyroid function or vitamin D metabolism such as thyroid hormone replacement, corticosteroids, anticonvulsants
• Allergy to vitamin D or methimazole
• Diagnosis of Hashitoxicosis or thyrotoxicosis (both TSH receptor antibody (TRAb) and thyroid-stimulating immunoglobulin (TSI) levels are negative)
• Participants under the age of 9 years at the time of diagnosis
• Pregnant participants
• Active or uncontrolled infections, other significant medical conditions deemed by the investigator to interfere with study participation or pose undue risk to the participant.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Dose Vitamin D2 + Methimazole; Participants in this arm will receive methimazole at a dose determined by their treating physician, according to standard clinical practice guidelines for pediatric Graves' disease. In addition, they will receive high-dose vitamin D2 (ergocalciferol) 50,000 IU orally weekly for the first 8 weeks, followed by 50,000 IU orally every two weeks for the remaining 16 weeks of the study.	Drug: Ergocalciferol 50,000 IU; Participants will receive ergocalciferol 50,000 IU oral capsules weekly for the first 8 weeks, followed by 50,000 IU every two weeks for the subsequent 16 weeks (total 24 weeks).; Drug: Methimazole; Methimazole is considered standard of care for pediatric Graves' disease. Dosing is determined and adjusted by the participant's treating physician
Placebo Comparator: Methimazole (with optional low dose Vitamin D2); Participants in this arm will receive methimazole at a dose determined by their treating physician, according to standard clinical practice guidelines for pediatric Graves' disease. Participants will have the option of taking up to 1000 IU of vitamin D2 daily, purchased over-the-counter, but this will not be provided by the study. This is to address potential vitamin D deficiency while maintaining a comparison group.	Drug: Methimazole; Methimazole is considered standard of care for pediatric Graves' disease. Dosing is determined and adjusted by the participant's treating physician

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility Metrics: Recruitment Rate	Percentage of eligible participants approached who consent to participate in the study. This metric will assess the efficiency of recruitment strategies.	through study completion, an average of 1 yea
Feasibility Metrics: Adherence Rate	Percentage of prescribed vitamin D doses taken by participants in the intervention arm. Adherence will be tracked via pill counts and participant self-report.	From enrollment to 24 week/6month follow up visit
Feasibility Metrics: Data Completeness	Percentage of completed data fields for key outcome measures (thyroid function tests, TSI levels, etc.). This will assess the quality and completeness of data collection.	From baseline data collection to the 24-week/6-month follow-up visit.
Feasibility Metrics: Implementation Barriers	A qualitative assessment of any challenges encountered during the study implementation (e.g., recruitment difficulties, adherence issues, logistical problems). This assessment will inform strategies for overcoming these barriers in a future, larger-scale RCT.	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Normalization and Thyroid function Trends	We hypothesize that patients receiving high-dose vitamin D will achieve normal TSH, T3, Free T4 and T4 levels significantly faster than those receiving methimazole alone. Thyroid function tests will be measured at baseline, 6, 12 and 24 weeks, and time to normalization will be compared between groups.	from enrollment to 24 week/6month follow up visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in TRAb and TSI Levels	We hypothesize that patients receiving high-dose vitamin D will experience a significantly greater percentage reduction in TSH R-Ab and TSI levels at 24 weeks compared to those receiving methimazole alone. Antibody levels will be measured at baseline and 24 weeks, and the percentage change from baseline will be compared between groups.	from enrollment to 24 week/6month visit

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Sharon Hyman, MD, Northwell Health

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: July 14, 2025
• First Submitted That Met QC Criteria: January 23, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: vitamin d; hyperthyroidism; graves disease
• Additional Relevant MeSH Terms: Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Exophthalmos; Orbital Diseases; Goiter; Thyroid Diseases; Graves Disease; Hyperthyroidism; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lipids; Azoles; Polycyclic Compounds; Imidazoles; Steroids; Fused-Ring Compounds; Sulfhydryl Compounds; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Ergocalciferols; Methimazole
• Other Study ID Numbers: 25-0285

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data from this pilot feasibility study will not be shared immediately due to the small sample size and the increased risk of participant re-identification. However, data sharing aligned with journal requirements will be considered upon publication of the study results. A detailed data sharing plan will be developed at that time, addressing ethical considerations and ensuring participant privacy while maximizing the scientific value of the data. This plan will outline the specific data to be shared (e.g., de-identified data, specific variables) and the process for requesting access.
• IPD Sharing Time Frame: Data sharing will be considered upon acceptance of the manuscript for publication in a peer-reviewed journal.
• IPD Sharing Access Criteria: Researchers may request access to the de-identified individual participant data by contacting Dr Sharon Hyman or Dr Sofya Ilmer. Requests will be reviewed based on scientific merit, adherence to data use agreements, and capacity to protect participant confidentiality. A data use agreement will be required. Data will be shared in a format compliant with relevant privacy regulations (e.g., HIPAA).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes