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

NCT ID: NCT03046927

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-19
• Study Completion Date: 2021-04-20

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.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Ergocalciferol

Intervention Type: DRUG

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

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

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

Intervention Type: DRUG

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

Intervention Type: OTHER

Other Intervention Names

Vitamin D

Eligibility Criteria

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.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Massachusetts, Worcester

OTHER

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Benjamin U. Nwosu, MD

OTHER

Sponsor Role: lead

Responsible Party

Benjamin U. Nwosu, MD

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Benjamin U Nwosu, MD

Role: PRINCIPAL_INVESTIGATOR

University of Massachusetts, Worcester

Locations

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1R21DK113353

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H00010550

Identifier Type: -

Identifier Source: org_study_id