Clinical trial NCT03406897: Pilot Study of OMEGA-3 and Vitamin D in High-Dose in Type I Diabetic Patients
Official title: A Pilot, Safety and Feasibility Trial of High-Dose Omega-3 Fatty Acids and High-Dose Cholecalciferol (Vitamin D) Supplementation in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus, Type 1
Hypoglycemia
Diabetes Mellitus
Diabetes, Autoimmune
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Diabetes Research Institute Foundation
First posted: 2018-01-23
Enrollment: 25
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: MMTT (Mixed Meal Tolerance Test)
timeFrame: Through study completion, and average of one year
Secondary outcomes:
measure: Hemoglobin A1c Level Reduction
timeFrame: Through study completion, and average of one year
measure: Reduction in Insulin Requirements
timeFrame: Through study completion, and average of one year
measure: Incidence of Adverse Events (AE)
timeFrame: Through study completion, and average of one year
Other outcomes:
Locations:
city: Miami
country: United States
facility: Diabetes Research Institute, University of Miami Miller School of Medicine
state: Florida
Study officials:
affiliation: Professor and Center Director of Diabetes Research Institute
name: Camillo Ricordi, M.D.
role: STUDY_DIRECTOR
References:
citation: Baidal DA, Ricordi C, Garcia-Contreras M, Sonnino A, Fabbri A. Combination high-dose omega-3 fatty acids and high-dose cholecalciferol in new onset type 1 diabetes: a potential role in preservation of beta-cell mass. Eur Rev Med Pharmacol Sci. 2016 Jul;20(15):3313-8.