Elemental Diet for Treatment of Inflammatory Bowel Disease in Patients With Chronic Granulomatous Disease

Background:

Bacteria that live inside the stomach and intestines are important for health. Chronic granulomatous disease (CGD) and inflammatory bowel disease (IBD) can make people have unhealthy bacteria. This can lead to gastrointestinal (GI) problems. Researchers want to see if people with CGD and IBD feel better when they change the bacteria in the stomach by following a special liquid diet.

Objective:

To see if an elemental diet can change the bacteria in the stomach and intestines of people with CGD and IBD. Also, to see if this helps GI symptoms.

Eligibility:

People ages 8-65 years with CGD, CGD-associated colitis, and IBD.

Design:

Participants will first be screened with:

Upper GI endoscopy and/or colonoscopy. A long, thin tube with a tiny camera at the end will be passed into the participant s body through the mouth or anus. Tissue will be collected. Participants will be sedated for the procedure. They will be sedated using a special mask or small plastic tube placed in an arm vein using a needle.

Participants will be put on the special diet for up to 4 weeks. They will stay in the hospital for the first 1-2 weeks. They will have check-ups. They will have blood, urine, and stool samples collected. They will keep a symptom diary to record how they feel and any GI symptoms.

Participants will have 2 follow-up visits. The first will be right after they finish the diet. The second will be 4 weeks later. They will have blood, urine, and stool samples collected. They will learn about re-introducing other foods into their diet.

Study Overview

• Status: Enrolling by invitation
• Conditions: Chronic Granulomatous Disease; Inflammatory Bowel Disease
• Intervention / Treatment: Other: Neocate Splash

Detailed Description

Chronic granulomatous disease (CGD) is a rare genetic immune disorder that results in recurrent and severe infections, and inflammatory dysregulation. For almost 50% of patients with CGD, this inflammation causes severe inflammatory bowel disease (IBD). However, treatment is long term and challenging as CGD-IBD is prone to relapse, and use of immune modulators must be balanced with increased risk of infectious complications. Conventional IBD (Crohn disease and ulcerative colitis) is likely caused by an inappropriate inflammatory response to intestinal microbes, which is influenced by the environment in a genetically susceptible host. While it is not yet clear if intestinal dysbiosis is a result or cause of intestinal inflammation, studies suggest that correcting intestinal dysbiosis may improve intestinal inflammation. Studies in patients with conventional IBD suggest that strict dietary restrictions can resolve symptoms of IBD and induce remission as effectively as glucocorticoids but without the side effects of those drugs. Because these diets alter the gut microbiome, they may serve as effective treatment for CGD-IBD.

In this study, we propose to treat 5 patients >= 8 years old who have CGD and IBD with 4 weeks of an elemental diet. Participants will stay as inpatients for up to 2 weeks and will return for follow-up at the end of the diet to begin tapering off and be reintroduced to normal food. The primary objective of this study is the evaluation of changes in the microbiome before and after the elemental diet. Secondary objectives are evaluations of tolerability and safety of the diet, along with changes in local and systemic markers of inflammation, and improvement of IBD symptoms as determined by reduction in Harvey-Bradshaw Index score.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

Individuals must meet all of the following criteria to be eligible for study participation:

• Aged 8-65 years.
• Have confirmed diagnoses of CGD, CGD-associated colitis, and IBD.
• Have a Simple Endoscopic Score for Crohn Disease (SES-CD) > 3 and/or HBI >= 5.
• Able to provide informed consent.
• Willing to allow storage of biological samples for future research.
• Willing to allow genetic testing on biological samples.
• Willing to be admitted as inpatient for up to 2 weeks to initiate the elemental diet.

EXCLUSION CRITERIA:

• Pregnancy.
• Active or ongoing infection that requires antibiotics other than the participant s known prophylaxis medications.
• Any condition that, in the opinion of the investigator, contraindicates participation in this study will be excluded from study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Participants will be on this diet for 4 weeks. The amount per serving will be determined on the basis of the participant s weight and caloric needs, as determined by a staff dietician.	Other: Neocate Splash; Neocate Splash is a hypoallergenic, amino acid based elemental liquid diet that is taken orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the relative abundance of proteobacteria in stool samples obtained after elemental diet.	Change in the relative abundance of proteobacteria in stool samples obtained after elemental diet.	Day 56

Secondary Outcome Measures

Outcome Measure	Time Frame
Unexpected AEs possibly, probably, or definitely related to the elemental diet.	Day 0 to 56
Ability to tolerate 4 weeks of elemental diet as measured by > 75% of caloric intake via elemental diet over the 4-week period.	Day 0 to 27
Weight loss.	Day 0 to 56
Initiation of antibiotics.	Day 0 to 56
Changes in fecal calprotectin, ESR, and CRP.	Day 56
Changes in the HBI at completion of the elemental diet and at 4 weeks after completion.	Day 28 and 56
Change in alpha and beta diversity after diet	Day 56

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Christa S Zerbe, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• Jones LB, McGrogan P, Flood TJ, Gennery AR, Morton L, Thrasher A, Goldblatt D, Parker L, Cant AJ. Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry. Clin Exp Immunol. 2008 May;152(2):211-8. doi: 10.1111/j.1365-2249.2008.03644.x.
• Magnani A, Brosselin P, Beaute J, de Vergnes N, Mouy R, Debre M, Suarez F, Hermine O, Lortholary O, Blanche S, Fischer A, Mahlaoui N. Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease. J Allergy Clin Immunol. 2014 Sep;134(3):655-662.e8. doi: 10.1016/j.jaci.2014.04.014. Epub 2014 Jun 27.
• van den Berg JM, van Koppen E, Ahlin A, Belohradsky BH, Bernatowska E, Corbeel L, Espanol T, Fischer A, Kurenko-Deptuch M, Mouy R, Petropoulou T, Roesler J, Seger R, Stasia MJ, Valerius NH, Weening RS, Wolach B, Roos D, Kuijpers TW. Chronic granulomatous disease: the European experience. PLoS One. 2009;4(4):e5234. doi: 10.1371/journal.pone.0005234. Epub 2009 Apr 21.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2021
• Primary Completion (Estimated): June 23, 2026
• Study Completion (Estimated): June 23, 2026

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (Actual): June 12, 2019

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 2, 2023
• Last Verified: November 30, 2023

More Information

Terms related to this study

• Keywords: Microbiome; Ulcerative Colitis; Inflammatory Bowel Disease; Crohn disease; Glucocorticoids
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Disease Attributes; Hematologic Diseases; Gastrointestinal Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Gastroenteritis; Leukocyte Disorders; Phagocyte Bactericidal Dysfunction; Chronic Disease; Inflammatory Bowel Diseases; Intestinal Diseases; Granuloma; Granulomatous Disease, Chronic
• Other Study ID Numbers: 190108; 19-I-0108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: .Human data generated in this study will be shared for future research as follows:@@@-De-identified data in an NIH-funded or approved public repository.@@@-De-identified data in another public repository. @@@-Identified data in the Biomedical Translational Research Information System (automatic for activities in the CC).@@@-De-identified or identified data with approved outside collaborators under appropriate agreements.
• IPD Sharing Time Frame: Data will be shared at the time of or shortly after publication.
• IPD Sharing Access Criteria: Requests for data will be reviewed and approved/disapproved by the PI.
• IPD Sharing Supporting Information Type: CSR

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