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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Ergocalciferol; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Ergocalciferol; 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; Other Names: Vitamin D
Placebo Comparator: 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	Other: Placebo; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic control (HbA1c)	Exploration of the effect of vitamin D supplementation on glycemic control during PCR by comparing HbA1c values across longitudinal measurements (at 0, 3, 6, 9, and 12 months).	12 months
Glucagon-like peptide-1 (GLP-1)	Investigation of the effect of vitamin D supplementation on GLP-1 and VDBP during PCR.	12 months
Differences in the duration of PCR in subjects with high-risk SNPs receiving vitamin D vs. placebo	Determination of whether a single nucleotide polymorphism (SNP)-based T1D genetic risk score influences the effect of vitamin D supplementation on PCR, and the magnitude of RBCF	12 months
Vitamin D Binding Protein (VDBP)	Investigation of the effect of vitamin D supplementation on VDBP during PCR.	12 months
Duration of Partial Clinical Remission (PCR)	Investigation of the effect of vitamin D on PCR in the first 12 months after the diagnosis of T1D	12 months

Collaborators and Investigators

• Sponsor: Benjamin U. Nwosu, MD
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Massachusetts, Worcester
• Investigators: Principal Investigator: Benjamin U Nwosu, MD, University of Massachusetts, Worcester

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2017
• Primary Completion (Actual): April 12, 2021
• Study Completion (Actual): April 20, 2021

Study Registration Dates

• First Submitted: February 1, 2017
• First Submitted That Met QC Criteria: February 5, 2017
• First Posted (Estimate): February 8, 2017

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 9, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Type 1 diabetes; vitamin D; honeymoon phase
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Ergocalciferols
• Other Study ID Numbers: H00010550; 1R21DK113353 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No.

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.: No