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

Phase 2

Completed

Conditions: Type 1 Diabetes

Interventions: Other: Placebo
Drug: Ergocalciferol

Registration Number: NCT03046927

Lead Sponsor: Benjamin U. Nwosu, MD

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

Inclusion Criteria

Age: 10-21 years.
Sex: male and female subjects will be enrolled.
Tanner stage: I-V.
T1D duration of <3 months (i.e., from first insulin injection) to ensure the inclusion of patients in PCR.
Presence of at least one diabetes-associated autoantibody.
Normal-weight, overweight-, and obese subjects with T1D
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

Subjects on weight altering medications, such as orlistat.
Subjects with eating disorders
Subjects on medications other than insulin that can affect blood glucose level.
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.
Subjects with systemic diseases other than T1D.
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.
Pregnant or breast-feeding female subjects.
The receipt of any investigational drug within 6 months prior to this trial.
Active malignant neoplasm.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Oral administration of placebo one capsule per week for 2 months; and then once every 2 weeks for 10 months in 20 subjects of 10-21yr with newly diagnosed T1D
Ergocalciferol	Ergocalciferol	Oral administration of 50,000 IU of ergocalciferol one capsule per week for 2 months; and then once every 2 weeks for 10 months in 20 subjects of 10-21yr with newly diagnosed T1D

Primary Outcome Measures

Name	Time	Method
Residual Beta-cell Function (RBCF)	Baseline to 12 months at 3 months interval	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.

Secondary Outcome Measures

Name	Time	Method
Change in Percent of HbA1c From Baseline Over Time During Partial Clinical Remission (PCR)	Baseline to 12 months	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.
Glucagon-like Peptide-1 (GLP-1)	Baseline to 12 months at 3 months interval	Investigation of the effect of vitamin D supplementation on GLP-1 during PCR.
Vitamin D Binding Protein (VDBP)	Baseline to 12 months at 3 months interval	Investigation of the effect of vitamin D supplementation on VDBP during PCR.
Effect of Vitamin D Supplementation on the Duration of Partial Clinical Remission (PCR) of Type 1 Diabetes	Baseline to12 months 3 monthly	Insulin dose-adjusted hemoglobin A1c (HbA1c) (IDAA1C)