Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04271774 |
| Other study ID # |
2018P002109 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2019 |
| Est. completion date |
December 2025 |
Study information
| Verified date |
October 2023 |
| Source |
Massachusetts General Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
GEMMA is a multicenter longitudinal observational study that follows children who are
genetically at-risk of developing autism for their first three years of life, seeking to
identify potential biomarkers predictive of autism development in the blood, stool, urine and
saliva. The biomarkers identified in this project will contribute to a better understanding
of the pathogenesis of ASD in at-risk children and possible solutions for alleviating and/or
preventing ASD and ASD-related symptoms in patients in the future.
Description:
The GEMMA study will address genomic, environmental, microbiome, and metabolomic factors that
may affect the development of autism spectrum disorders (ASD).
Genome: The project will study children who have a first-degree relative (sibling) with ASD
so that investigators can understand how their genes may contribute to whether they develop
ASD or not. A number of genetic variants identified to date occur in genes encoding
glycosylated extracellular proteins and in enzymes directly involved in glycosylation.
Investigators will perform whole genome sequencing in the subgroup of children that will
develop ASD in order to learn more about these specific genes and also to identify other
genes that may be involved in ASD pathogenesis. The genetic variant landscape will be mapped
and variants will be annotated and interpreted based on all contextual information available.
This effort will enable the identification of patient- and cohort-specific variations that
can then be further refined into biomarker signatures and optimized into predictive and
diagnostic markers of ASD.
Environment: When infants enroll in the study, investigators will record information about
their environment including whether they were born vaginally or by Cesarean section and
whether they have received antibiotics. Over time, investigators will also consider other
parts of the infant's medical, dietary and social history including feeding modality
(breastfeeding versus formula feeding), illnesses, infections, antibiotic use, diet and
growth to understand whether any of this information is related to ASD development. This data
will be updated monthly until each enrolled infant reaches 3 years of age, yielding a
valuable compilation of information that will provide insight on how environmental changes
affect whether the child develops ASD or not.
Microbiome: The human gut, compromised of the small and large intestine, is home to many
types of bacteria. These bacteria help to break down and digest food, provide the body with
energy, and make vitamins that the body need to thrive. This diverse community of bacteria is
called the gut microbiome, which is known to play a large role in the development of the
immune system. A main goal of the GEMMA study is to understand how the microbiome is affected
by factors such as food intake or antibiotic drugs, and how this may affect the development
of ASD. Investigators hope to learn more about this relationship by studying the members of
the gut microbiome before and after autism development in the subset of enrolled infants who
will develop ASD. The project will compare microbiota of ASD children with and without GI
symptoms to determine whether different microbiota composition and differentially expressed
bacterial genome perturb intestinal barrier function and immune response, leading to ASD in
genetically at-risk infants. By doing this, the project will uncover patterns in the gut
microbiome that may help investigators to predict who will develop ASD before it happens.
Metabolome: The processes that occur in the gut, such as the digestion of foods and
production of vitamins, create products that are called metabolites. The specific metabolites
that humans produce differ from person to person and depend on many factors, including genes,
members of the gut microbiome, and food choices. The collection of metabolites produced by a
sample is called the metabolome. The project will study the metabolomes of different infants
while taking note of any changes to their environment and monitoring them for ASD. Studying
the metabolites in this way is called metabolomics. In doing this, investigators hope to find
patterns, or specific metabolomic profiles, that might predict when someone may develop ASD
before it happens.
