Clinical trial NCT03911843: Omega-3 and Vitamin D Supplements in Childhood T1D
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type 1 Diabetes Mellitus
Keywords: omega3
T1D remission period
honeymoon period
AA/EPA ratio
Lead sponsor: Azienda Ospedaliero Universitaria Maggiore della Carita
Sponsor class: OTHER
Collaborators: name: University of Eastern Piedmont
First posted: 2019-04-11
Enrollment: 64
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months
timeFrame: 12 months
measure: HbA1c Percentage
timeFrame: 12 months
measure: Number of Participants With Insulin Demand Adjusted for HbA1c %(IDAA1c) <9
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Pediatric Clinic of AOU Novara
name: Francesco Cadario, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cadario F, Savastio S, Ricotti R, Rizzo AM, Carrera D, Maiuri L, Ricordi C. Administration of vitamin D and high dose of omega 3 to sustain remission of type 1 diabetes. Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):512-515. doi: 10.26355/eurrev_201801_14203.
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.