Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers

Neurodevelopmental Disorders Clinical Trial

— GD-BRAIN  

Official title:

Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers (GD-BRAIN)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03032991
• Other study ID #: SAF2015-69265
• Status: Recruiting
• Phase: N/A
• First received: January 13, 2017
• Last updated: January 23, 2017
• Start date: January 2016
• Est. completion date: December 2020

Study information

• Verified date: January 2017
• Source: Universidad de Murcia
• Contact: Elvira Larqué, Dr
• Phone: 0034868884239
• Email: elvirada[@]um.es
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The prospective multicenter study GD-Brain provides a better knowledge on the basis of neurological impairment in children born to mothers with gestational diabetes (GDM). GDM modifies placental structure and affect materno-fetal nutrient transfer. Docosahexaenoic acid (DHA) play an important role on neurodevelopment, and it is reduced in venous cord blood of newborns born to GDM. In previous studies, we have already demonstrated impaired DHA fetal levels not only using label fatty acids with stable isotopes administrated to pregnant women, but also in observational studies in GDM as the prevention of obesity study (PREOBE study) in Granada and other similar study in Murcia. The impaired cord DHA levels were associated to disturbed neurodevelopment in these children during the first year of life. However, it is uncertain the mechanisms underlying this impaired materno-fetal DHA transfer and implications for later life.

The recent publication in Nature Journal of a selective transmembrane carrier for DHA in brain named "major facilitator superfamily domain 2a" (MFSD2a) open new expectations. We detected disturbed MFSD2a levels in placentas from GDM which could be due to structural problems in this organ; inflammation, oxidation and metabolic changes related to diabetes might affect MFSD2a activity. Moreover, it is difficult to know whether disturbed MFSD2a levels in placenta may also indicate altered levels of this carrier in the brain from children born to GDM mothers, which could contribute to neurodevelopment impairment in these subjects. Recent studies also indicate that obesity alters the biosynthesis of eicosanoids derived from DHA, with a decrease of protectins and resolvin of D-series, which have powerful anti-inflammatory properties.

The main aim of this study is to analyse potential differences on neurodevelopment, and brain structure and functioning, in children 8 years old born to GDM respect to those born to healthy normoweight mothers, as well as to identify early biomarkers consistently related to neurodevelopment from early stages of life.

Description:

We will contact to participants from the PREOBE study and Murcia's cohorts study to get involved a total of 174 children at 8 years of age. The results from neurodevelopment evaluation by neuropsychological testing, neurological functions rhythms and neuroimaging (fMRI and DTI) at 8 years old will be associated to clinical and metabolic data recorded during pregnancy.

As secondary aim, we would discern whether the decrease on DHA levels in offspring of GDM at birth is associated to disturbed neurodevelopment at 8 years old.

The impact of maternal diabetes on placental MFSD2a and children's resolvin and protectins derived from DHA will be measured in urine samples at 8 years old.

Gut microbiota composition and function will be also studied to detect its role in the potential disturbances regarding the production of anti-inflammatory mediators.

A part from the clinical study, we will perform an intervention trial using animal models. Gestational rats with diabetes and control rats will be treated with antioxidants and adipoRon in order to delay neuro-degeneration in these animals because of the diabetes, as well as their influence on MFSD2a levels in placenta and brain. All these studies may provide to the industry of valuable information to improve nutritional supplements during gestation or infancy to avoid potential delay of cognitive functions in offspring of diabetic mothers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 174
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 9 Years

Eligibility

Inclusion Criteria:

• Children from healthy pregnancies and GDM pregnancies from the ^PREOBE study and GDM Murcia study.

Exclusion Criteria:

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes Mellitus in Childbirth
• Neurodevelopmental Disorders

Locations

Country	Name	City	State
Spain	Elvira Larqué	Murcia

Sponsors (2)

Lead Sponsor	Collaborator
Universidad de Murcia	Universidad de Granada

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Microbiome	Metagenome	8 years old
Other	Maturation of circadian rhythm	Analysis of the circadian rhythm of temperature, activity and sleep	8 years old
Other	Nutritional evaluation	Dietary assessment by food frequency questionnaire and by 3 day of dietary record	8 years old
Other	Physical activity	questionnaires	8 years old
Other	Physical Activity	Accelerometers will be used also to record activity of the subjects	8 years old
Primary	Neuropsychological battery	Neuropsychological battery to cover different neuropsychological domains: processing speed, memory, attention, language, executive functions, and behaviour (parent-completed measure).	8 years old
Primary	Neuroimaging ( functional MRI)	Anatomical magnetic resonance imaging (fMRI)	8 years
Primary	Electroencephalography (EEG)	Stereotyped electrophysiological response to several external stimulus	8 years
Secondary	Fatty acids	Fatty acid profile in oral mucose	8 years old
Secondary	Metabolomic	Prostaglandins, thromboxans, isoprostanes, resolvin in urine samples	8 years old