Pilot Study of OMEGA-3 and Vitamin D in High-Dose in Type I Diabetic Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pilot, Safety and Feasibility Trial of High-Dose Omega-3 Fatty Acids and High-Dose Cholecalciferol (Vitamin D) Supplementation in Type 1 Diabetes

Conditions
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Diabetes Mellitus, Type 1, Hypoglycemia, Diabetes Mellitus, Diabetes, Autoimmune

Intervention / Treatment
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* Drug: Cholecalciferol
* Drug: Omega 3 fatty acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients must meet all of the following criteria to be eligible to participate in this study: Subjects or their parents if under 18 years old must be able to understand and provide informed consent. Males and females, 6-65 years of age. For new onset T1D subjects, ≤180 days from T1D diagnosis at the time of randomization with a MMTT stimulated C-peptide peak level ≥0.2 ng/ml prior to randomization. For established T1D subjects, >180 days and ≤10 years of T1D duration at the time of randomization and MMTT stimulated C-peptide peak level ≥0.2 ng/ml prior to 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 autoantibodies (if patient has been treated with insulin for less than 2 weeks). 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 Potential participants must not meet any of the following exclusion criteria: Inability or unwillingness of a participant or their parents to give written informed consent or comply with study protocol. BMI>30 Kg/m2. Contra-indications to Omega-3 Fatty Acids and/or Vitamin-D (e.g., knowledge of hypersensitivity to drugs or its excipients, allergies with fish or shellfish etc.). 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 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. Subjects on weight altering medications, such as Orlistat. Subjects with eating disorders 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. People who chronically take drugs that affect bleeding time, such as anticoagulants (blood thinners) or nonsteroidal anti-inflammatory drugs (NSAIDs), will not qualify to enroll in the study. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 6 weeks of randomization. Use of investigational drugs within 4 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. History of gastroparesis or other severe gastrointestinal disease. History or diagnosis of malignancy with the exception of a history of localized basal or squamous cell carcinoma. There is conflicting evidence about whether omega-3 fatty acids found in seafood and fish oil might increase the risk of prostate cancer. Until additional research on the association of omega-3 consumption and prostate cancer risk is conducted, subjects with family history of prostate cancer in a first-degree relative will be excluded from the study. 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 a 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. All patients who have coagulation, bleeding, or blood disorders will be excluded due to the effect of high dose of Omega 3 Fatty Acids on coagulation and bleeding process.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Omega-3 and Vitamin D Combination<br>The treatment arm A includes Omega-3 Fatty Acids and Cholecalciferol (Vitamin D) supplement. | Drug: Cholecalciferol<br>* Oral Administration<br>* Other names: Vitamin D;Drug: Omega 3 fatty acid<br>* Oral Administration<br>* Other names: Omega 3;|
| Active Comparator: Vitamin D Only<br>The treatment arm B (control group) will receive only Cholecalciferol (Vitamin D) supplement. | Drug: Cholecalciferol<br>* Oral Administration<br>* Other names: Vitamin D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMTT (Mixed Meal Tolerance Test) | Stimulated (90 minute sample of a MMTT) C-peptide greater or equal to baseline level. | Through study completion, and average of one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c Level Reduction | Reduction in HbA1c at the one year visit compared to baseline | Through study completion, and average of one year | 
| Reduction in Insulin Requirements | Reduction in insulin requirement at the 1 year visit compared to baseline | Through study completion, and average of one year | 
| Incidence of Adverse Events (AE) | Incidence of adverse events (AE) comparable to general diabetes population | Through study completion, and average of one year |