Trial Outcomes & Findings for Omega-3 and Vitamin D Supplements in Childhood T1D (NCT NCT03911843)

Last Updated: 2021-04-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

64 participants

Primary outcome timeframe

12 months

Results posted on

2021-04-19

Participant Flow

The recruitment started 03/17/2017 with the enrollment of the first patient, and ended on 06/08/2019 with the end of the omega-3 supplementation period of the last enrolled patient. All participants were introduced since the beginning of T1D to tailored insulin therapy, to Mediterranean diet (according to a standardized item detailed in reference), and received 1000 IU/day of vitamin D supplementation.

Participant milestones

Participant milestones
Measure	CASES New T1D Onsets 2017 All the New T1D Onsets 2017 received a further supplementation of ultra refined fish oil, enriched in LC-PUFA omega 3, containing standardized concentrations EPA + DHA (2:1), at 60 mg/kg/day. The supplementation with omega 3 started within 3th and 6th months after the clinical T1D onset and lasted one year.	CONTROLS Previous T1D Onsets All Previous T1D Onsets (2014-2016) receiving vitamin D and Mediterranean diet without omega 3 supplementation, were continuously recruited. Retrospectively their available data from 3th and 6th months from the clinical onset to T1D, for the following year, were compared.
Overall Study STARTED	26	38
Overall Study COMPLETED	22	37
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	CASES New T1D Onsets 2017 All the New T1D Onsets 2017 received a further supplementation of ultra refined fish oil, enriched in LC-PUFA omega 3, containing standardized concentrations EPA + DHA (2:1), at 60 mg/kg/day. The supplementation with omega 3 started within 3th and 6th months after the clinical T1D onset and lasted one year.	CONTROLS Previous T1D Onsets All Previous T1D Onsets (2014-2016) receiving vitamin D and Mediterranean diet without omega 3 supplementation, were continuously recruited. Retrospectively their available data from 3th and 6th months from the clinical onset to T1D, for the following year, were compared.
Overall Study Adverse Event	2	0
Overall Study Protocol Violation	2	0
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Omega-3 and Vitamin D Supplements in Childhood T1D

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CASES n=26 Participants The T1D onsets were eligible subjects, of which 26/64 new onsets 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 60 mg/kg/day for 12 months. The supplementation with omega 3 started within 3th and 6th months of T1D clinical onset and lasted one year. They had been introduced to the Mediterranean diet according to a standardized item and received 1000 IU/day of vitamin D supplementation since the beginning of T1D	CONTROLS n=38 Participants The Previous T1D onsets, 38/64 subjects joined to the study as controls (CONTROLS). They received vitamin D supplementation 1000 IU/day and Mediterranean diet according to a standardized item since the onset of T1D, without omega 3; retrospectively their available data from 3th and 6th months of overt disease for the following year, were compared	Total n=64 Participants Total of all reporting groups
Age, Categorical <=18 years	26 Participants n=5 Participants	38 Participants n=7 Participants	64 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	8.7 years STANDARD_DEVIATION 4.6 • n=5 Participants	8.8 years STANDARD_DEVIATION 3.6 • n=7 Participants	8.75 years STANDARD_DEVIATION 4 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	20 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	18 Participants n=7 Participants	30 Participants n=5 Participants
Race/Ethnicity, Customized Italian	20 Participants n=5 Participants	33 Participants n=7 Participants	53 Participants n=5 Participants
Race/Ethnicity, Customized North Africa	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Albania	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Pakistan	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Italy	26 participants n=5 Participants	38 participants n=7 Participants	64 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	CASES New T1D Onsets 2017 n=22 Participants All the New T1D Onsets 2017 received a further supplementation of ultra refined fish oil, enriched in LC-PUFA omega 3, containing standardized concentrations EPA + DHA (2:1), at 60 mg/kg/day. The supplementation with omega 3 started within 3th and 6th months after the clinical T1D onset and lasted one year.	CONTROLS Previous T1D Onsets n=37 Participants All Previous T1D Onsets (2014-2016) receiving vitamin D and Mediterranean diet without omega 3 supplementation, were continuously recruited. Retrospectively their available data from 3th and 6th months from the clinical onset to T1D, for the following year, were compared.
Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months Daily insulin need	0.49 IU/Kg/day Standard Deviation 0.2	0.63 IU/Kg/day Standard Deviation 0.1
Daily Insulin Need (IU/Kg/Day) and Daily Insulin Pre-meal Demand (Pre-meal IU/Kg/Day) at 12 Months Daily Insulin Pre-meal Demand	0.22 IU/Kg/day Standard Deviation 0.1	0.34 IU/Kg/day Standard Deviation 0.1

PRIMARY outcome

Timeframe: 12 months

percentage of glycated hemoglobin measured through the high-performance liquid chromatography (HPLC).

Outcome measures

Outcome measures
Measure	CASES New T1D Onsets 2017 n=22 Participants All the New T1D Onsets 2017 received a further supplementation of ultra refined fish oil, enriched in LC-PUFA omega 3, containing standardized concentrations EPA + DHA (2:1), at 60 mg/kg/day. The supplementation with omega 3 started within 3th and 6th months after the clinical T1D onset and lasted one year.	CONTROLS Previous T1D Onsets n=37 Participants All Previous T1D Onsets (2014-2016) receiving vitamin D and Mediterranean diet without omega 3 supplementation, were continuously recruited. Retrospectively their available data from 3th and 6th months from the clinical onset to T1D, for the following year, were compared.
HbA1c Percentage	7.4 percentage of HbA1c Standard Deviation 1	7.8 percentage of HbA1c Standard Deviation 1

PRIMARY outcome

Timeframe: 12 months

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).

Outcome measures

Outcome measures
Measure	CASES New T1D Onsets 2017 n=22 Participants All the New T1D Onsets 2017 received a further supplementation of ultra refined fish oil, enriched in LC-PUFA omega 3, containing standardized concentrations EPA + DHA (2:1), at 60 mg/kg/day. The supplementation with omega 3 started within 3th and 6th months after the clinical T1D onset and lasted one year.	CONTROLS Previous T1D Onsets n=37 Participants All Previous T1D Onsets (2014-2016) receiving vitamin D and Mediterranean diet without omega 3 supplementation, were continuously recruited. Retrospectively their available data from 3th and 6th months from the clinical onset to T1D, for the following year, were compared.
Number of Participants With Insulin Demand Adjusted for HbA1c %(IDAA1c) <9	12 Participants	7 Participants

Adverse Events

CASES New T1D Onsets 2017

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

CONTROLS Previous T1D Onsets

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	CASES New T1D Onsets 2017 n=26 participants at risk；n=22 participants at risk All the New T1D Onsets 2017 received Mediterranean diet, vitamin D 1000 IU/day, and a further supplementation of ultra refined fish oil, enriched in LC-PUFA omega 3, containing standardized concentrations EPA + DHA (2:1), at 60 mg/kg/day. The supplementation with omega 3 started within 3th and 6th months after the clinical T1D onset and lasted one year.	CONTROLS Previous T1D Onsets n=38 participants at risk；n=37 participants at risk All Previous T1D Onsets (2014-2016) receiving vitamin D and Mediterranean diet without omega 3 supplementation, were continuously recruited. Retrospectively their available data from 3th and 6th months from the clinical onset to T1D, for the following year, were compared.
Gastrointestinal disorders persistent diarrhea	3.8% 1/26 • Number of events 1 • The observation interval of side effects was in each case into the period of omega-3 supplementation (T0-T12), lasting 12 months, and into a comparable period in the controls. 1. Chronic diarrhea lasting 2 weeks of duration in a female case. The administration of supplementation with omega 3 was interrupted 2. Isolated thyrotropine deficiency, in a teenager girl with pre-existing autoimmune thyroiditis. The administration of supplementation with omega 3 was interrupted 3. Activated partial thromboplastin time (observable entity) without clinical symptoms observed. At the end of the study, one year after the start of omega 3 supplementation	0.00% 0/38 • The observation interval of side effects was in each case into the period of omega-3 supplementation (T0-T12), lasting 12 months, and into a comparable period in the controls. 1. Chronic diarrhea lasting 2 weeks of duration in a female case. The administration of supplementation with omega 3 was interrupted 2. Isolated thyrotropine deficiency, in a teenager girl with pre-existing autoimmune thyroiditis. The administration of supplementation with omega 3 was interrupted 3. Activated partial thromboplastin time (observable entity) without clinical symptoms observed. At the end of the study, one year after the start of omega 3 supplementation
Endocrine disorders transient suppression of TRH	3.8% 1/26 • Number of events 1 • The observation interval of side effects was in each case into the period of omega-3 supplementation (T0-T12), lasting 12 months, and into a comparable period in the controls. 1. Chronic diarrhea lasting 2 weeks of duration in a female case. The administration of supplementation with omega 3 was interrupted 2. Isolated thyrotropine deficiency, in a teenager girl with pre-existing autoimmune thyroiditis. The administration of supplementation with omega 3 was interrupted 3. Activated partial thromboplastin time (observable entity) without clinical symptoms observed. At the end of the study, one year after the start of omega 3 supplementation	0.00% 0/38 • The observation interval of side effects was in each case into the period of omega-3 supplementation (T0-T12), lasting 12 months, and into a comparable period in the controls. 1. Chronic diarrhea lasting 2 weeks of duration in a female case. The administration of supplementation with omega 3 was interrupted 2. Isolated thyrotropine deficiency, in a teenager girl with pre-existing autoimmune thyroiditis. The administration of supplementation with omega 3 was interrupted 3. Activated partial thromboplastin time (observable entity) without clinical symptoms observed. At the end of the study, one year after the start of omega 3 supplementation
Blood and lymphatic system disorders an extension of the aPTT clotting	3.8% 1/26 • Number of events 1 • The observation interval of side effects was in each case into the period of omega-3 supplementation (T0-T12), lasting 12 months, and into a comparable period in the controls. 1. Chronic diarrhea lasting 2 weeks of duration in a female case. The administration of supplementation with omega 3 was interrupted 2. Isolated thyrotropine deficiency, in a teenager girl with pre-existing autoimmune thyroiditis. The administration of supplementation with omega 3 was interrupted 3. Activated partial thromboplastin time (observable entity) without clinical symptoms observed. At the end of the study, one year after the start of omega 3 supplementation	0.00% 0/38 • The observation interval of side effects was in each case into the period of omega-3 supplementation (T0-T12), lasting 12 months, and into a comparable period in the controls. 1. Chronic diarrhea lasting 2 weeks of duration in a female case. The administration of supplementation with omega 3 was interrupted 2. Isolated thyrotropine deficiency, in a teenager girl with pre-existing autoimmune thyroiditis. The administration of supplementation with omega 3 was interrupted 3. Activated partial thromboplastin time (observable entity) without clinical symptoms observed. At the end of the study, one year after the start of omega 3 supplementation

Additional Information

Dr. Francesco Cadario, Head of the Pediatric Diabetology service

Azienda Ospedaliero-Universitaria di Novara, Italy

Phone: +39 347 226 6507

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place