Clinical trial NCT03046927: Vitamin D and Residual Beta-Cell Function in Type 1 Diabetes
Official title: Vitamin D and Residual Beta-Cell Function in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type 1 Diabetes
Keywords: Type 1 diabetes
vitamin D
honeymoon phase
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
Collaborators: name: University of Massachusetts, Worcester
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-02-08
Enrollment: 48
Sex: ALL
Minimum age (years): 10
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 12-month randomized, double-blind, placebo-controlled, parallel design trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Residual Beta-cell Function (RBCF)
timeFrame: Baseline to 12 months at 3 months interval
Secondary outcomes:
measure: Change in Percent of HbA1c From Baseline Over Time During Partial Clinical Remission (PCR)
timeFrame: Baseline to 12 months
measure: Glucagon-like Peptide-1 (GLP-1)
timeFrame: Baseline to 12 months at 3 months interval
measure: Vitamin D Binding Protein (VDBP)
timeFrame: Baseline to 12 months at 3 months interval
measure: Effect of Vitamin D Supplementation on the Duration of Partial Clinical Remission (PCR) of Type 1 Diabetes
timeFrame: Baseline to12 months 3 monthly
Other outcomes:
Locations:
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
Study officials:
affiliation: University of Massachusetts, Worcester
name: Benjamin U Nwosu, MD
role: PRINCIPAL_INVESTIGATOR
References: