Vitamin D and Residual Beta-Cell Function in Type 1 Diabetes

Benjamin U. Nwosu, MD48 enrolled

Overview

This project is designed to study the role of vitamin D supplementation on the honeymoon phase of type 1 diabetes in children who are on standardized insulin treatment. The results could lead to significant changes in the approach to the early phase of type 1 diabetes with a strong emphasis on prolonging the honeymoon phase by using vitamin D and maintaining these patients on a standardized insulin regimen. The overall goal is to reduce the long-term complications of type 1 diabetes.

Prolonging the duration of the partial clinical remission (PCR), or 'honeymoon' phase, of type 1 diabetes (T1D) improves glycemic control and reduces long-term complications. Recent studies suggest the exciting possibility that vitamin D supplementation, a safe and easy-to-implement therapy in children, may lengthen PCR and increase residual beta cell function (RBCF). However, existing studies employed a suboptimal vitamin D dose or lacked a standardized insulin treatment protocol, precluding solid conclusions and preventing the field from moving forward with translation to clinical practice. This trial's rationale is to securely establish the effect of an adequate dose of vitamin D on PCR and RBCF. We hypothesize that vitamin D will increase RBCF and prolong PCR. The primary aim is to determine the effect of adjunctive vitamin D on RBCF and PCR in youth with T1D maintained on a standardized insulin protocol. We propose a 12-month randomized, double-blind, placebo-controlled, parallel design trial of ergocalciferol vs. placebo in 40 subjects of 10-21 years with newly-diagnosed T1D. The primary outcome is the change over time in stimulated C-peptide (a measure of RBCF). Secondary outcomes include change over time in insulin-dose-adjusted-hemoglobin-A1c (HbA1c) (IDAA1C; a measure of PCR), HbA1c, and total daily dose of insulin. Mechanistic studies will explore whether beneficial effects of vitamin D are associated with increased GLP-1 levels or decreased inflammatory markers, and whether response to vitamin D is impacted by T1D-risk polymorphisms. If our hypotheses are true, these findings may completely alter the approach to the early management of T1D, with strong emphasis on prolonging the honeymoon phase using a readily available and easily affordable vitamin D while maintaining these patients on a standardized insulin treatment regimen.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Type 1 Diabetes

Interventions

ErgocalciferolDRUG

Each subject on the experimental arm will receive one capsule of ergocalciferol per week for 2 months; and then once every 2 weeks for 10 months

PlaceboOTHER

Each subject on the placebo arm will receive one capsule of placebo per week for 2 months; and then once every 2 weeks for 10 months

Eligibility

Sex: ALLMin age: 10 YearsMax age: 21 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age: 10-21 years. 2. Sex: male and female subjects will be enrolled. 3. Tanner stage: I-V. 4. T1D duration of \<3 months (i.e., from first insulin injection) to ensure the inclusion of patients in PCR. 5. Presence of at least one diabetes-associated autoantibody. 6. Normal-weight, overweight-, and obese subjects with T1D 7. Fasting serum C-peptide level of \>0.1 nmol/L (0.3 ng/mL)1; or 2-hour post-meal stimulated C-peptide level of 0.2 nmol/L (≥0.6 ng/mL). Exclusion Criteria: 1. Subjects on weight altering medications, such as orlistat. 2. Subjects with eating disorders 3. Subjects on medications other than insulin that can affect blood glucose level. 4. Subjects with 25-hydroxyvitamin D \[25(OH)D\] levels of \>70 ng/mL, as this may lead to vitamin D toxicity in the study subjects. 5. Subjects with systemic diseases other than T1D. 6. Subjects with recurrent diabetic ketoacidosis (\>2 episodes since the diagnosis of T1D or in the preceding 3 months); or \>2 episodes of severe hypoglycemia in the preceding 3 mo. 7. Pregnant or breast-feeding female subjects. 8. The receipt of any investigational drug within 6 months prior to this trial. 9. Active malignant neoplasm.

Locations (1)

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Outcomes

Primary Outcomes

Residual Beta-cell Function (RBCF)

Investigation of the effect of vitamin D on residual beta cell function (RBCF) in the first 12 months after the diagnosis of T1D by using stimulated C-peptide levels to quantify RBCF.

Time frame: Baseline to 12 months at 3 months interval

Secondary Outcomes

Change in Percent of HbA1c From Baseline Over Time During Partial Clinical Remission (PCR)

Effect of vitamin D supplementation on glycemic control during the partial clinical remission phase as shown by the change in percent HbA1c from baseline across longitudinal measurements at 0, 3, 6, 9, and 12 months.

Time frame: Baseline to 12 months

Glucagon-like Peptide-1 (GLP-1)

Investigation of the effect of vitamin D supplementation on GLP-1 during PCR.

Time frame: Baseline to 12 months at 3 months interval

Vitamin D Binding Protein (VDBP)

Investigation of the effect of vitamin D supplementation on VDBP during PCR.

Time frame: Baseline to 12 months at 3 months interval

Effect of Vitamin D Supplementation on the Duration of Partial Clinical Remission (PCR) of Type 1 Diabetes

Insulin dose-adjusted hemoglobin A1c (HbA1c) (IDAA1C)

Time frame: Baseline to12 months 3 monthly

Data from ClinicalTrials.gov

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