Diabetes, Autoimmune, Diabetes Mellitus, Diabetes Mellitus, Type 1, Hypoglycemia
Conditions
Brief summary
The investigator propose to test the safety and efficacy of a regimen that combines Omega-3 Fatty Acids and Vitamin D in a design that considers timing and duration of administration in relation to their effects and predicted synergies.
Detailed description
These agents may afford promote sustained immune regulation, reduce inflammation, and provide support for the residual beta cell mass. This integrated therapeutic regimen addresses major pathogenic mechanisms in T1D (Type 1 Diabetes) and thus represents a rational and well supported approach to preserve insulin secretion in T1D (Type 1 Diabetes). This approach could halt the disease progress, preserve β-cell function and hopefully reduce dose of insulin required to manage T1D (Type 1 Diabetes). The investigator hypothesizes that Omega-3 Fatty Acids and Vitamin D, administered to patients with newly or established T1D (Type 1 Diabetes) and residual stimulated C-peptide secretion will be safe and may preserve insulin secretion.
Interventions
DRUGCholecalciferol
Oral Administration
DRUGOmega 3 fatty acid
Oral Administration
Sponsors
Diabetes Research Institute Foundation
Rodolfo Alejandro
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study is a two-arm, open label, randomized trial. All four groups will receive standard intensive diabetes treatment with insulin and dietary management. Group I: Fourteen (14) adults (18-65 years) of established T1D \> 6 months (\>180 days) and up to 10 years of T1D duration Group II: Fourteen (14) adults (18-65 years) of new-onset T1D diagnosed within last 6 months (≤ 180 days) Group III: Fourteen (14) children (6-17 years) of established T1D \> 6 months (\>180 days) and up to 10 years of T1D duration Group IV: Fourteen (14) children (6-17 years) of new-onset T1D diagnosed within last 6 months (≤ 180 days) Participants in each group will be randomly assigned in a 1:1 ratio to receive either one year of high dose Omega-3 fatty acids and Vitamin D combination (Arm A) or Vitamin D alone (Arm B). Both arms will receive Vitamin D supplementation.
Eligibility
Sex/Gender
ALL
Age
6 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following criteria to be eligible to participate in this study: * Subject must be able to understand and provide informed consent. * Males and females, 6-17 years for children and 18-65 years of age for adult group. * For new onset T1D - from onset to 6 months (180 days) post-diagnosis at the time of randomization. * For established T1D - At least 6 months and up to 10 years from the diagnosis at the time of randomization. * Affected by T1D, according to ADA standard criteria, and confirmed by positivity of at least one T1D-associated autoantibody, to GAD65, IA-2, ZnT8, or insulin autoantibody (if patient has been treated with insulin for less than 2 weeks). * T1D must be treated with insulin (except if participant is in Honeymoon period/phase). * Stimulated C-peptide peak level, at the baseline 1 visit MMTT, ≥ 0.2 ng/ml. * Female subjects of childbearing potential must have a negative pregnancy test upon study entry. * Adequate venous access to support study required blood draws.
Exclusion criteria
Patients must not meet any of the following criteria to be eligible to participate: * Inability or unwillingness of a participant to give written informed consent or comply with study protocol. * BMI\>30 kg/m2. * Contra-indications to any of the drugs used in the trial (as per package insert, e.g., knowledge of hypersensitivity to drugs or its excipients). * Uncompensated heart failure, fluid overload, myocardial infarction or liver disease or severe impairment of a vital organ within the last 6 weeks before enrollment. * Any of the following laboratory findings indicating hemoglobin \<10.0 g/dL; leukocytes \<3,000/μL; neutrophils \<1,500/μL; lymphocytes \<800/μL; platelets \<100,000/μL. * Any sign or diagnosis of significant chronic active infection (e.g., hepatitis, tuberculosis, EBV, or CMV), or screening laboratory evidence consistent with a significant chronic active infection (such as positive for HIV, IGRA test for TB, or hepatitis B-C). * Ongoing acute infections, e.g., acute respiratory tract, urinary tract, or gastrointestinal tract infections. * Ongoing or anticipated use of diabetes medications other than insulin. * Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening. * Recent recipient of any licensed or investigational live attenuated vaccine(s) within 6 weeks of randomization. * Use of investigational drugs within 3 months of participation. * Concomitant therapy with immunosuppressive drugs, immunomodulators, or cytotoxic agents, or previous therapy less than 3 months from randomization. * History or diagnosis of malignancy, with the exception of a history of localized basal or squamous cell carcinoma. * History of gastroparesis or other severe gastrointestinal disease.. * Presence of an allograft. * AST, ALT or Alkaline Phosphatase \>2 times upper limit of normal or total bilirubin \>1.5 times upper limit of normal. * History of mental illness deemed to be clinically unstable or any situation that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements. * History of illicit drug or alcohol abuse. * Pregnancy or ongoing breastfeeding for women; unwillingness or inability of both females and males of childbearing age to use a reliable and effective form of contraception, for the entire duration of the study. * Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in MMTT (Mixed Meal Tolerance Test) 90 Min C-peptide | Baseline and 1-Year Visit | Stimulated (90-minute sample of a MMTT) C-peptide at the 1-year visit greater or equal to baseline level measured by ng/mL. Change in 90-minute C-peptide between baseline and 1-year visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin A1c Level | Baseline and 1-Year Visit | Change in HbA1c between baseline and 1-year |
| Change in Insulin Requirements | Baseline and 1-Year Visit | Difference in insulin requirement at the 1-year visit compared to baseline measured in units/kg/day |
| Number of Adverse Events (AE) | Through study completion, and average of one year | Number of adverse events (AE) comparable to general diabetes population |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omega-3 and Vitamin D Combination The treatment arm A includes Omega-3 Fatty Acids and Cholecalciferol (Vitamin D) supplement.
Cholecalciferol: Oral Administration
Omega 3 fatty acid: Oral Administration | 12 |
| Vitamin D Only The treatment arm B (control group) will receive only Cholecalciferol (Vitamin D) supplement.
Cholecalciferol: Oral Administration | 15 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Omega-3 and Vitamin D Combination | Vitamin D Only | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 10 Participants | 12 Participants | 22 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White, Hispanic | 5 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized White, Non-Hispanic | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment United States | 12 participants | 15 participants | 27 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 15 |
| other Total, other adverse events | 8 / 12 | 8 / 15 |
| serious Total, serious adverse events | 0 / 12 | 2 / 15 |
Outcome results
Primary
Change in MMTT (Mixed Meal Tolerance Test) 90 Min C-peptide
Stimulated (90-minute sample of a MMTT) C-peptide at the 1-year visit greater or equal to baseline level measured by ng/mL. Change in 90-minute C-peptide between baseline and 1-year visit
Time frame: Baseline and 1-Year Visit
Population: Group A: 7/12 subjects completed 1year follow-up. Group B: 8/15 subjects completed 1year follow up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Omega-3 and Vitamin D Combination | Change in MMTT (Mixed Meal Tolerance Test) 90 Min C-peptide | -1.23 ng/mL |
| Vitamin D Only | Change in MMTT (Mixed Meal Tolerance Test) 90 Min C-peptide | -0.62 ng/mL |
Secondary
Change in Hemoglobin A1c Level
Change in HbA1c between baseline and 1-year
Time frame: Baseline and 1-Year Visit
Population: Group A: 7/12 subjects completed 1year follow-up. Group B: 8/15 subjects completed 1year follow up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Omega-3 and Vitamin D Combination | Change in Hemoglobin A1c Level | 0.00 percentage of HbA1c |
| Vitamin D Only | Change in Hemoglobin A1c Level | -0.55 percentage of HbA1c |
Secondary
Change in Insulin Requirements
Difference in insulin requirement at the 1-year visit compared to baseline measured in units/kg/day
Time frame: Baseline and 1-Year Visit
Population: Group A: 7/12 subjects completed 1year follow-up. Group B: 8/15 subjects completed 1year follow up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Omega-3 and Vitamin D Combination | Change in Insulin Requirements | 0.16 units/kg/day |
| Vitamin D Only | Change in Insulin Requirements | 0.15 units/kg/day |
Secondary
Number of Adverse Events (AE)
Number of adverse events (AE) comparable to general diabetes population
Time frame: Through study completion, and average of one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omega-3 and Vitamin D Combination | Number of Adverse Events (AE) | 31 number of adverse events |
| Vitamin D Only | Number of Adverse Events (AE) | 28 number of adverse events |