ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03046927
Recruitment Status : Recruiting
First Posted : February 8, 2017
Last Update Posted : October 24, 2017
Sponsor:
Information provided by (Responsible Party):
Benjamin U. Nwosu, 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.

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 12-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 : October 19, 2017
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : July 31, 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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 Name: 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



Primary Outcome Measures :
  1. Residual beta-cell function (RBCF) [ Time Frame: 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 :
  1. Glycemic control (HbA1c) [ Time Frame: 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).

  2. Glucagon-like peptide-1 (GLP-1) [ Time Frame: 12 months ]
    Investigation of the effect of vitamin D supplementation on GLP-1 and VDBP during PCR.

  3. Differences in the duration of PCR in subjects with high-risk SNPs receiving vitamin D vs. placebo [ Time Frame: 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

  4. Vitamin D Binding Protein (VDBP) [ Time Frame: 12 months ]
    Investigation of the effect of vitamin D supplementation on VDBP during PCR.

  5. Duration of Partial Clinical Remission (PCR) [ Time Frame: 12 months ]
    Investigation of the effect of vitamin D on PCR in the first 12 months after the diagnosis of T1D



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   10 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03046927


Contacts
Contact: Benjamin U Nwosu, M.D. 5083347872 Benjamin.Nwosu@umassmemorial.org
Contact: Carol A Ciccarelli, RN 5088562828 Carol.Ciccarelli@umassmed.edu

Locations
United States, Massachusetts
Benjamin Nwosu Recruiting
Worcester, Massachusetts, United States, 01609-1123
Contact: Benjamin U Nwosu, MD    508-752-5477    Benjamin.Nwosu@umassmemorial.org   
Contact: Danielle Pichette    508-856-3077    Danielle.Pichette-Patsky@umassmed.edu   
Principal Investigator: Benjamin U Nwosu, MD         
Sub-Investigator: Carol A Ciccarelli, RN         
Sub-Investigator: Bruce A Barton, PhD         
Sub-Investigator: Yahui Kong, PhD         
Sub-Investigator: Jody Fleshman, RD         
Sub-Investigator: Susan Hutchinson, RN         
Sub-Investigator: Laura C Alonso, MD         
Sub-Investigator: Sanaa Ayyoub, MD         
University of Massachusetts Medical School Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Carol Ciccarelli    508-856-2828    Carol.Ciccarelli@umassmed.edu   
Contact: Danielle Pichette    508-856-3077    Danielle.Pichette-Patsky@umassmed.edu   
Sponsors and Collaborators
University of Massachusetts, Worcester
Investigators
Principal Investigator: Benjamin U Nwosu, MD University of Massachusetts, Worcester

Responsible Party: Benjamin U. Nwosu, Associate Professor, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT03046927     History of Changes
Other Study ID Numbers: H00010550
First Posted: February 8, 2017    Key Record Dates
Last Update Posted: October 24, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No.

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

Keywords provided by Benjamin U. Nwosu, University of Massachusetts, Worcester:
Type 1 diabetes
vitamin D
honeymoon phase

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Vitamins
Vitamin D
Ergocalciferols
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents