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

Sponsor

Benjamin U. Nwosu, MD (Other)

Overall Status

Completed

CT.gov ID

NCT03046927

Collaborator

University of Massachusetts, Worcester (Other), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

Actual Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Drug: Ergocalciferol Other: Placebo	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

12-month randomized, double-blind, placebo-controlled, parallel design trial12-month randomized, double-blind, placebo-controlled, parallel design trial

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.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 19, 2017

Actual Primary Completion Date :

Apr 12, 2021

Actual Study Completion Date :

Apr 20, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Residual beta-cell function (RBCF) [12 months]
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

Glycemic control (HbA1c) [12 months]
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).
Glucagon-like peptide-1 (GLP-1) [12 months]
Investigation of the effect of vitamin D supplementation on GLP-1 and VDBP during PCR.
Differences in the duration of PCR in subjects with high-risk SNPs receiving vitamin D vs. placebo [12 months]
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
Vitamin D Binding Protein (VDBP) [12 months]
Investigation of the effect of vitamin D supplementation on VDBP during PCR.
Duration of Partial Clinical Remission (PCR) [12 months]
Investigation of the effect of vitamin D on PCR in the first 12 months after the diagnosis of T1D

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.