Omega-3 and Vitamin D Supplements in Childhood T1D

Study Overview
=================
Brief Summary
-----------------
The study was conducted in 64 patients with T1D of which 26 had the onset in 2017, and 38 in 2016, 2015 and 2014. All received vitamin D 1000 IU /day since disease's onset. Moreover in the 2017 group omega-3 were supplemented, starting within 3 and 6 months from the disease's outbreak, and those were considered cases; the other 38 were enrolled as controls. Four cases and one control dropped out. Finally in 59/64 were compared data of glycosylated hemoglobin percentage (HbA1c%), average insulin daily requirement (IU/Kg/day), and IDAA1c [Insulin Daily dose Adjusted for HbA1c, a surrogate index of residual endogen insulin secretion, calculated as insulin daily dose (IU/Kg/24 h) x 4 + HbA1c%] at recruitment (T0), and 3 (T3), 6 (T6), 12 (T12) months after. T0 in cases was at the start of supplementation of omega-3, and consequently 3, 6 and 12 months after; in controls were found data in clinical records of outpatient beginning from the 3rd month and 3-6-12 months thereafter. Then 22 cases and 37 controls were compared.

Detailed Description
-----------------
Was assessed the comparability of cases and controls at baseline for gender, age, body weight, HbA1c% and device for insulin therapy. The preparation of omega-3 administered was a highly purified fish oil to avoid pollutants, containing a mixture of omega-3 long chain fatty acids standardized for contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a 2: 1 ratio, in capsules or in liquid form. The liquid preparation was used in the case of difficulties in swallowing capsules or concomitant celiac disease because it was certified as gluten-free (Ener Zone Omega 3 RX® Equipe Enervit). The preparations contained antioxidants to preserve omega-3 LCFA, tocopherol (1 mg in 1 g of omega-3 LCFA), palmitate, and rosemary extract. EPA and DHA were administered at 50-60 mg/kg/day for 12 months. The investigation of Arachidonic Acid (AA)/EPA ratios was performed in cases on recruitment (T0), and repeated after 3 (T3), 6 (T6), and 12 months (T12). Cholecalciferol supplementation was fixed at 1000 IU/day (25 mcg/day), both in cases and controls. Vitamin D level was determined as 25(OH)D level at the clinical onset of T1D, at T0, T3, T6, and T12 in cases, and at clinical onset of controls.

Official Title
-----------------
Omega 3 Long Chain Polyunsaturated Fatty Acids, Enriched Mediterranean Diet and Vitamin D Supplementation in Childhood Type 1 Diabetes: One Year Case-cohort Study

Conditions
-----------------
Type 1 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: omega-3 supplementation
* Drug: Vitamin D supplementation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All T1D patients aged 1-18 years whose disease onset had been in 2017, 2016, 2015, 2014 affering to the Pediatric Diabetology of AOU Novara (Italy) written consents of parents without assumption of omega 3 supplementation before 2017 Exclusion Criteria: renal cysts sarcoidosis histoplasmosis hyperparathyroidis lymphoma tuberculosis Patients treated with drugs that could affect immunity or glucose metabolism, including corticosteroids, ciclosporin and tacrolimus

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A cohort study was performed in 2017, in all T1D patients 1-18 years old with onset in the years 2014-2017. Supplementation with omega3 was proposed to all subjects with onset in 2017. Patients with onset in 2014-2015-2016 were enrolled only as control subjects. The work was performed on retrospectively collected data in medical records for patients with start of the disease in 2014-2016. Patients enrolled since 2017 have been studied prospectively.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CASES<br>Of eligible subjects, 26/64 started an intervention program with Ω-3 (CASES). The intervention consisted in supplementation with highly purified Ω-3, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a dose of 50-60 mg/kg/day for 12 months | Drug: omega-3 supplementation<br>* Supplementation with Ω-3, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a dose of 50-60 mg/kg/day for 12 months, currently underway or completed after 12 months of omega-3 administration, in 22/64 T1D children<br>* Other names: Ener Zone Omega 3 RX® Equipe Enervit;Drug: Vitamin D supplementation<br>* Cholecalciferol 1000 IU/die<br>|
| Active Comparator: CONTROLS<br>Others 38/64 subjects joined to the study as data contributors, and were entered as controls (CONTR). | Drug: Vitamin D supplementation<br>* Cholecalciferol 1000 IU/die<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months | The Daily Insulin Needs (IU/Kg/day), and the Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/day) respectively represent the average total (sum of boluses and basal) and average pre-meal (sum of pre-meal boluses) insulin doses administered in one day to each patient. They have been calculated over a week, and were expressed in International Units / Kg of weight, higher values mean a worse outcome. | 12 months | 
| HbA1c Percentage | percentage of glycated hemoglobin measured through the high-performance liquid chromatography (HPLC). | 12 months | 
| Number of Participants With Insulin Demand Adjusted for HbA1c %(IDAA1c) <9 | The IDAA1c (insulin daily dose adjusted for glycosylated hemoglobin percentage) was calculated as HbA1c percentage + average daily insulin dose (IU/kg/24 h) x 4. A score <9 meet definition of partial remission and Residual Endogenic Insulin Secretion (REIS). IDAA1c represents a surrogate index of insulin secretion and of metabolic control. In a scale from 5 to 12, higher score mean a worse outcome (e.g. <5.5 is expected in a normal individual, <9 in an individual in partial remission. See reference). | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
omega3, T1D remission period, honeymoon period, AA/EPA ratio