Clinical trial NCT03850600: Modulating Early Life Microbiome Through Dietary Intervention in Crohn's Disease
Official title: The MELODY Trial: Modulating Early Life Microbiome Through Dietary Intervention in Crohn's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Crohn Disease
Pregnancy
Keywords: Microbiota
Diet
Immune System
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: The Leona M. and Harry B. Helmsley Charitable Trust
name: University of Massachusetts, Worcester
First posted: 2019-02-22
Enrollment: 194
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study design is a three-arm, prospective, pre-post intervention trial. Crohn's Disease (CD) patients at 27-29 weeks of pregnancy will self-select to Arm 1 or Arm 2. Controls will be in Arm 3.

1. Arm 1 (diet-CD): 8-10 weeks of dietary intervention (n=66)
2. Arm 2 (no-diet-CD): usual diet with no intervention (n=66)
3. Arm 3 (no-diet-control): unaffected controls at the same gestational stage will follow their usual diet and no intervention (n=66).
Primary purpose: SUPPORTIVE_CARE

Brief summary: The MELODY Trial: Modulating Early Life Microbiome through Dietary Intervention in Crohn's Disease, will test whether a non-invasive dietary intervention during pregnancy can improve the gut microbiota composition in both pregnant Crohn's disease patients and their babies during the sensitive time window of infant immune system development, and whether this can lead to decreased risk of maternal disease relapse postpartum and decreased functional gastrointestinal disorders and gut inflammation in their babies. Through this trial, the study team hopes to better understand the origin of the initial gut bacterial colonization in babies, providing potential intervention targets to prevent Crohn's disease development in high risk individuals.

Detailed description: The study design is a three-arm, prospective, pre-post intervention trial. Crohn's Disease (CD) patients at 27-29 weeks of pregnancy will self-select to Arm 1 or Arm 2. Controls will be in Arm 3.

1. Arm 1 (diet-CD): 8-10 weeks of dietary intervention (n=66)
2. Arm 2 (no-diet-CD): usual diet with no diet intervention (n=66)
3. Arm 3 (no-diet-control): unaffected controls at the same gestational stage will follow their usual diet and no intervention (n=66).

The goal of this study is to prospectively test the hypothesis that a non-invasive dietary intervention during the last trimester of pregnancy could beneficially shift the microbiome of CD patients and their babies, hereby promoting a healthier immune system during a critical time of the immune system development. Particularly, the study team will test whether favorable diet-driven changes in the microbiome can lead to a reduced risk of postpartum relapse and lower gut inflammation in the offspring.

Stool, saliva, breast milk and umbilical cord blood samples will be collected, and questionnaires administered. Self-selected participants to Arm 1 will adopt a specified diet, which will be adapted to address specific needs of third trimester pregnancy without compromising the diet principles. Subjects will receive nutritional counseling and training, and compliance to dietary recommendations will be recorded.

Analysis will be performed to correlate dietary change and assessed changes in quality of life with microbial composition in the gut and with circulating markers of inflammation in moms. The study team will also compare the effect of diet vs. non-diet on babies' microbiome and the impact of the early life microbiome in levels of inflammatory markers after 1-year of partum.

This study will help better understand the origin of the initial bacterial colonization in high-risk babies, providing potential intervention targets for primary CD prevention. The study team will also generate an extensive collection of serial samples and longitudinal clinical data, including identification of specific dietary components correlated with certain functional and quantitative bacterial patterns for future investigations. This study will help create new opportunities to foster a healthy microbiome in high risk babies of microbiome and immunity-mediated diseases, thereby hopefully reducing their risk later in life.

Eligibility criteria: Inclusion Criteria:

* Capacity to sign informed consent
* At least 18 years old
* Singleton pregnancy of less than 27-29 weeks gestation
* English-speaking

Exclusion Criteria:

* Inability to provide informed consent
* HIV/AIDS
* Multi-fetus pregnancy
* Fetal chromosomal or structural abnormalities
* Active infection (including chorioamnionitis or sepsis)
* Alcohol use disorder
* Diagnosis of diabetes, renal disease, or intrauterine growth restriction
* Non-English speaking
* Active perianal or extraintestinal disease
* Antibiotic or steroid treatment at recruitment
* Scheduled cesarean section prior to gestational week 37

Primary outcomes:
measure: Change in overall number of proteobacteria
timeFrame: Baseline and 4 Years
Secondary outcomes:
measure: Calprotectin level
timeFrame: 4 Years
measure: Harvey Bradshaw index (HBI)
timeFrame: 4 Years
measure: SF-12
timeFrame: 4 Years
measure: The Rome IV Criteria
timeFrame: 3 months
measure: The Center for Epidemiologic Studies Depression Scale-Revised (CESD-R)
timeFrame: 4 Years
measure: The Bristol Stool Form Scale
timeFrame: 4 Years
measure: Alternative Healthy Eating Index
timeFrame: 4 Years
Other outcomes:
Locations:
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Inga Peter, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Massachusetts, Worcester
name: Barbara Olendzki, RD,MPH, LDN
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Massachusetts, Worcester
name: Ana Maldonado-Contreras, PhD
role: PRINCIPAL_INVESTIGATOR
References: