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

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

Sponsors

Lead sponsor: Benjamin U. Nwosu, MD

Collaborator: University of Massachusetts, Worcester
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Source University of Massachusetts, Worcester
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.

Overall Status Active, not recruiting
Start Date October 19, 2017
Completion Date March 31, 2021
Primary Completion Date March 31, 2021
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Residual beta-cell function (RBCF) 12 months
Secondary Outcome
Measure Time Frame
Glycemic control (HbA1c) 12 months
Glucagon-like peptide-1 (GLP-1) 12 months
Differences in the duration of PCR in subjects with high-risk SNPs receiving vitamin D vs. placebo 12 months
Vitamin D Binding Protein (VDBP) 12 months
Duration of Partial Clinical Remission (PCR) 12 months
Enrollment 48
Condition
Intervention

Intervention type: Drug

Intervention name: Ergocalciferol

Description: 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

Arm group label: Ergocalciferol

Other name: Vitamin D

Intervention type: Other

Intervention name: Placebo

Description: 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

Arm group label: Placebo

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.

Gender: All

Minimum age: 10 Years

Maximum age: 21 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Benjamin U Nwosu, MD Principal Investigator University of Massachusetts, Worcester
Location
facility University of Massachusetts Medical School
Location Countries

United States

Verification Date

March 2020

Responsible Party

Responsible party type: Sponsor-Investigator

Investigator affiliation: University of Massachusetts, Worcester

Investigator full name: Benjamin U. Nwosu, MD

Investigator title: Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Ergocalciferol

Arm group type: Experimental

Description: 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

Arm group label: Placebo

Arm group type: Placebo Comparator

Description: 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

Acronym PCR
Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: 12-month randomized, double-blind, placebo-controlled, parallel design trial

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking description: Ergocalciferol and placebo will be prepared as identical capsules by Boulevard Pharmaceutical Compounding Center. Randomization will be conducted by the Investigational Drug Services (IDS), UMMS, using a randomization scheme generated by Dr. Barton. Randomization will be 1:1 (ergocalciferol: placebo) and will use a permuted block design with blocking for every 2 or 4 subjects (at random). IDS will maintain blinding information and PI will contact IDS for emergency unblinding.

Source: ClinicalTrials.gov