Modulating Early Life Microbiome Through Dietary Intervention in Crohn's Disease

The MELODY Trial: Modulating Early Life Microbiome Through Dietary Intervention in Crohn's Disease

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pregnancy; Crohn Disease
• Intervention / Treatment: Other: Diet-CD

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.

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diet-CD; dietary intervention: 8-10 weeks of diet intervention	Other: Diet-CD; CD patients will self-select into the intervention arm to follow the diet for 8-10 weeks during their third trimester of pregnancy.; Other Names: Diet Arm
No Intervention: No-Diet-CD; Usual diet with no intervention
No Intervention: No-Diet-Control; Unaffected controls at the same gestational stage will follow usual diet and no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in overall number of proteobacteria	Change in overall number of proteobacteria in pregnant CD patients at 4 years as compared to baseline	Baseline and 4 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calprotectin level	Calprotectin is a stool marker of inflammation	4 Years
Harvey Bradshaw index (HBI)	Assessments of CD symptom severity	4 Years
SF-12	Quality of life will be assessed using the SF-12. Mental and physical functioning is assessed by the Medical Outcomes Study Short Form 12 (SF-12) Health Survey. The questions in the SF-12 target eight dimensions of health and are weighted and summed to provide two composite measures, the Physical Composite Scale and Mental Composite Scale (PCS and MCS). The PCS and MCS are scored to range from 0 to 100, with 0 indicating the lowest level of health and 100 indicating the highest level of health.	4 Years
The Rome IV Criteria	The Rome IV Criteria for Functional Gastrointestinal Disorders in Infants will be used to assess infant's functional gastrointestinal disorders at 3 months of age. The Rome IV is a validated diagnostic criteria used to improve clinical care in infants and toddlers, adequately diagnose functional gastrointestinal disorders in order to provide proper treatment, and improve homogeneity in research study design.	3 months
The Center for Epidemiologic Studies Depression Scale-Revised (CESD-R)	The CES-D is a 20-item measure assessing symptoms of depression based on a 4-point Likert scale ranging from 0 -3, with higher score indicating more depression. and depressive disorder. The symptoms it measures are those defined by the American Psychiatric Association Diagnostic and Statistical Manual (DSM-V) for a major depressive episode.	4 Years
The Bristol Stool Form Scale	A validated 7 point scale used extensively in clinical practice and research for classification of stool form. The scale is from 1-7 and a higher score indicates looser stool. A score of 1 is classified as "separate hard lumps, like nuts (hard to pass), while a score of 7 is classified as "Watery, no solid pieces (entirely liquid)."	4 Years
Alternative Healthy Eating Index	Alternative Healthy Eating Index (AHEI) - total score ranging from 2.5 (least desirable) to 87.5 (most desirable) dietary pattern	4 Years

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: University of Massachusetts, Worcester; The Leona M. and Harry B. Helmsley Charitable Trust
• Investigators: Principal Investigator: Inga Peter, PhD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Barbara Olendzki, RD,MPH, LDN, University of Massachusetts, Worcester; Principal Investigator: Ana Maldonado-Contreras, PhD, University of Massachusetts, Worcester

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2019
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: February 15, 2019
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (Actual): February 22, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Microbiota; Diet; Immune System
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: GCO 18-2246

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No