Oral N-acetylglucosamine in Crohn's Disease

Not Applicable

Not yet recruiting

• Conditions: Crohns Disease
• Interventions: Drug: N-Acetylglucosamine (GlcNAc)

• Registration Number: NCT07225998
• Lead Sponsor: Johns Hopkins University

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.

Study Timeline

• Study First Submitted: 2025-10-29
• Status Verified: 2025-11
• Study First Submitted QC: 2025-11-05
• Last Update Submitted: 2025-11-05
• Study First Posted: 2025-11-10
• Last Update Posted: 2025-11-10
• Study Start: 2026-02-01
• Primary Completion: 2027-06-30
• Study Completion: 2027-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Participants with Crohn's disease and carry ZIP8 391-Thr (heterozygous or homozygous carriers)	N-Acetylglucosamine (GlcNAc)	N-acetylglucosamine
Participants with Crohn's disease who do not carry ZIP8 391-Thr	N-Acetylglucosamine (GlcNAc)	N-acetylglucosamine

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of oral GlcNAc as assessed by number of participants that initiate new CD therapy	Week 0, 6, 13; Washout Week 16	Monitoring of exacerbation of Crohn's disease (CD) activity, defined as Initiation of new CD therapy due to symptom worsening.
Safety and tolerability of oral GlcNAc as assessed by number of CD associated hospitalizations	Week 0, 6, 13; Washout Week 16	Monitoring of exacerbation of Crohn's disease (CD) activity, defined as CD-associated hospitalization (e.g. for bowel obstruction, intra-abdominal abscess)
Safety and tolerability of oral GlcNAc as assessed by number of CD associated surgeries	Week 0, 6, 13; Washout Week 16	Monitoring of exacerbation of Crohn's disease (CD) activity, defined as CD-associated surgery (e.g. ileocecal resection)
Safety and tolerability of oral GlcNAc as assessed by adverse events grades 3-5	Week 0, 6, 13; Washout Week 16	Monitoring for adverse events graded as CTCAE grades 3-5.

Secondary Outcome Measures

Name	Time	Method
Mean change in Short Crohn's Disease Activity Index (sCDAI)	Week 0, 6, 13; Washout Week 16	Patient reported disease activity index: sCDAI score range from 0 to 600; scores \<150 define remission, 150 to 219 mild activity, 220 to 450 moderate activity, and greater than 450 severe activity.
Mean Change in Harvey-Bradshaw Index (HBI) score	Week 0, 6, 13; Washout Week 16	Patient reported disease activity index: Mean change in scores from baseline and follow-up time points. The activity index is comprised of 5 items. General well being (0-4), abdominal pain (0-3), number of liquid stools per day (no maximum score), presence of an abdominal mass on physical exam (0-3), and complications (1 point per item). The total score is the sum of the individual parameters with scores less than 5 consistent with clinical remission. The minimum score is 0 and there is no pre-specified maximum score as it depends on the number of liquids stools; HBI score of \</= 4 will be considered clinical remission); reduction of \>/= 3 points (clinical response).
Mean Change in FACIT-Fatigue Patient-reported measure (Fatigue)	Week 0, 6, 13; Washout Week 16	Patient-reported measure. Mean change in FACIT-Fatigue scores from baseline (Week 0) to final intervention (Week 13), with a clinical significant threshold set at \>/= 4 points. Score ranges from 0 to 52 with higher scores indicating worse fatigue.
Mean Change in Fecal calprotectin	Week 0, 6, 13; Washout Week 16	Measure of inflammation. Mean change in fecal calprotectin (%) from baseline to follow-up
Mean change in serum C-Reactive Protein (CRP)	Week 0, 6, 13; Washout Week 16	Measure of inflammation: CRP (ng/ml) from baseline to follow-up
Change in panel-based blood inflammatory cytokines	Week 0, 6, 13; Washout Week 16	Measure of inflammation: Change in panel-based blood inflammatory cytokines (pg/ml) measures from baseline to follow-up.
Mean change in sCD14	Week 0, 6, 13; Washout Week 16	Measure of intestinal permeability sCD14 (pg/ml). Mean change in sCD14 from baseline to follow-up.
Change in serum N-glycome	Week 0, 6, 13; Washout Week 16	Measure of glycosylation Serum N-glycome (%): Change in Serum N-glycome from baseline to follow-up
Change in saliva N-glycome	Week 0, 6, 13; Washout Week 16	Measure of glycosylation: Change in saliva N-glycome (%) from baseline to follow-up.
Mean change in serum UDP-GlcNAc	Week 0, 6, 13; Washout Week 16	Measure of glycosylation: Serum UDP-GlcNAc (uM). Mean change in serum UDP-GlcNAc from baseline to follow-up.
Change in T cell N-glycan branching	Week 0, 6, 13; Washout Week 16	Measure of glycosylation: Change in T cell N-glycan branching (%) from baseline to follow-up
Change in T cell activity/responsiveness	Week 0, 6, 13; Washout Week 16	Measure of glycosylation: Change in T cell activity/responsiveness (%) from baseline to follow-up
Change in Fecal mucins	Week 0, 6, 13; Washout Week 16	Measure of glycosylation: Change in fecal mucins (%) from baseline to follow-up
Mean Change in Simple Ultrasound Activity (SUS-CD) Score Disease activity measured by intestinal ultrasound	Week 0, 13	Disease activity: Mean change in simple ultrasound activity score (includes bowel wall thickness and color Doppler signals) for Crohn's disease at Week 13. Score range 0-5 with 0-1 indicating normal or very mild disease; 2-3 moderate disease; 4-5 severe active disease.

Trial Locations

Locations (1)

Johns Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States