Oral N-acetylglucosamine in Crohn's Disease

NCT ID: NCT07225998

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-01
• Study Completion Date: 2027-10-31

Brief Summary

This study is a clinical trial of oral N-acetylglucosamine (GlcNAc) in patients with Crohn's disease (CD). This study includes two study groups divided by gene variation in a transporter protein that regulates manganese levels. This genetic variant increases the risk of Crohn's disease (especially involving the ileum) and is carried by approximately 10% of individuals with Crohn's disease. This genetic variant lowers manganese levels, and manganese is important in a cellular process called glycosylation, therefore, glycosylation is changed. Glycosylation in the gut controls the barrier function, interactions with the bugs in the gut, and immune function - all important in Crohn's disease. In this study, the investigators will test if this problem with glycosylation can be targeted by giving GlcNAc. GlcNAc is a key ingredient for glycosylation, and it is currently marketed as a dietary supplement in the United States.

Detailed Description

While many new medications improved care for patients with Crohn's disease, clinical remission is only achieved in ~40% of patients - a therapeutic ceiling that has not changed in 20 years. These data underscore the need for new treatment strategies and (the investigators hypothesize) greater focus on personalized medicine using factors like genetics.

This study is a clinical trial of oral N-acetylglucosamine (GlcNAc) in patients with Crohn's disease. The investigators are aiming for approximately half of the participants to carry a genetic variant in a gene called ZIP8. ZIP8 regulates levels of manganese and the variant lowers levels of manganese; manganese levels may also be reduced for reasons other than just ZIP8 genetics - including variation in dietary intake, water sources, and inflammation - therefore, the investigators are also enrolling participants who do not have the ZIP8 variant. Manganese is a nutrient absorbed from food that is required for glycosylation, but direct supplementation of excess manganese may carry risk of neurologic side effects. An alternative approach is to supplement with GlcNAc, the critical building block of glycosylation that regulates intestinal health and inflammation. GlcNAc is preferred given its positive safety profile and prior small studies in patients with inflammatory bowel disease.

Key study information:

• The investigators will check if participants carry the ZIP8 variant at study enrollment. (Approximately 10% of patients with Crohn's disease carry the variant.)
• This is an open-label study, meaning participants will receive active drug (GlcNAc) and never placebo.
• GlcNAc is provided to participants as a powder that the participant mixes in a small amount of water 3 times per day.
• GlcNAc is a naturally-occurring substance found in nature and tastes sweet when mixed with water.
• The study runs for 16 weeks. There are brief weekly check-ins and 5 in-person visits.
• The investigators will ask participants to provide blood, stool, and saliva samples for a total of 5 times.
• Participants will be paid to participate in the study (total $100); there are no costs to participants.

Conditions

Crohns Disease

Keywords

Crohns disease; manganese; GlcNAc; N-acetylglucosamine; ZIP8 protein; SLC39A8 gene; genetics; glycosylation disorder

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants with Crohn's disease and carry ZIP8 391-Thr (heterozygous or homozygous carriers)

N-acetylglucosamine

Group Type: EXPERIMENTAL

N-Acetylglucosamine (GlcNAc)

Intervention Type: DRUG

Participants will gradually increase the dose of GlcNAc to 12 g/day (in 3 divided daily doses) over 2 weeks and take drug through week 13.

Participants with Crohn's disease who do not carry ZIP8 391-Thr

N-acetylglucosamine

Group Type: EXPERIMENTAL

N-Acetylglucosamine (GlcNAc)

Intervention Type: DRUG

Participants will gradually increase the dose of GlcNAc to 12 g/day (in 3 divided daily doses) over 2 weeks and take drug through week 13.

Interventions

N-Acetylglucosamine (GlcNAc)

Participants will gradually increase the dose of GlcNAc to 12 g/day (in 3 divided daily doses) over 2 weeks and take drug through week 13.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Between 13 and 80 years of age
• Diagnosis of CD involving ileum (Montreal Criteria L1) or ileocolonic disease (Montreal Criteria L3) of any disease behavior
• Willing to undergo genetic testing for ZIP8 genotype
• On maintenance dosing of any CD treatment for >/= 8 weeks
• Prednisone or equivalent dose of ≤20 mg with plans to taper over first 6 weeks of study
• No antibiotics within 2 weeks of study start
• Willing to provide informed consent
• Willing to participate in all at-home and clinic-based follow-up
• Willing to provide most recent endoscopy and imaging results; when possible, access to prior pathology specimens
• Willing to use all forms of FDA approved contraception (female participants of child-bearing age)

Exclusion Criteria

• Have taken GlcNAc or glucosamine in the previous 3 months
• Allergy to shellfish
• Dose >20 mg of prednisone or equivalent at screening
• Antibiotics within 2 weeks
• History of type 1 diabetes, inadequately controlled type 2 diabetes (HbA1c>6.5%), type 2 diabetes on insulin
• History of peripheral vascular disease, coronary artery disease, stroke, transient ischemic attack
• History of cancer
• History of organ transplant
• History of bleeding disorder
• History of chronic respiratory disorder, including asthma
• History of chronic renal failure
• History of chronic liver disease
• History of seizure disorder
• Pregnant, less than 6 months postpartum, breastfeeding, or attempting to conceive

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leona M. & Harry B. Helmsley Charitable Trust

UNKNOWN

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joanna Melia, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Countries

United States

Central Contacts

Joanna MP Melia, MD

Role: CONTACT

Phone: 410-502-1559

Email: jpeloqu2@jhmi.edu

Facility Contacts

Joanna MP Melia, MD

Role: primary

Lynn Kobeissi, MD

Role: backup

References

Salvatore S, Heuschkel R, Tomlin S, Davies SE, Edwards S, Walker-Smith JA, French I, Murch SH. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79. doi: 10.1046/j.1365-2036.2000.00883.x.

Reference Type: BACKGROUND

PMID: 11121904 (View on PubMed)

Tomar V, Kang J, Lin R, Brant SR, Lazarev M, Tressler C, Glunde K, Zachara N, Melia J. Aberrant N-glycosylation may be a therapeutic target in carriers of a common and highly pleiotropic variant in the manganese transporter ZIP8. HGG Adv. 2025 Sep 16;7(1):100517. doi: 10.1016/j.xhgg.2025.100517. Online ahead of print.

Reference Type: BACKGROUND

PMID: 40963256 (View on PubMed)

Other Identifiers

2604-09127

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRB00533883

Identifier Type: -

Identifier Source: org_study_id