Oral N-acetylglucosamine in Crohn's Disease

Part of paid clinical trials in Baltimore, Maryland.

Sponsor
Johns Hopkins University
Study ID
NCT07225998
Phase
PHASE2
Status
Not Yet Recruiting

Notify me when recruiting opens

Save your spot on the interest list for this study. We'll keep your details with this study so our team can follow up when recruiting opens.

Not yet recruiting

Add your contact details and location so we can keep your interest tied to this study.

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • N-Acetylglucosamine (GlcNAc) — DRUG
    This is a placebo-controlled, cross-over design. The sequence in which the participant receives the GlcNAc or placebo is randomized. Participants will take GlcNAc 2 grams three times daily or placebo (glucose 2 grams three times daily) for 6 weeks. There will then be a 3 week washout period and then cross-over to GlcNAc or placebo for 6 weeks. Participants will be followed for 3 weeks off all drug/placebo to complete the study at week 18.

Study Details

Protein glycosylation is a critical post-translational modification that regulates protein trafficking and protein-protein interactions impacting a host of physiological processes. There is a growing appreciation of glycosylation defects in chronic human diseases, including Crohns disease. Crohns disease (CD), and the related condition of ulcerative colitis, are chronic inflammatory bowel diseases (IBD) that impact 3.1 million Americans. While the development of medications has revolutionized care of CD patients, 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 CD treatment strategies. The investigators are focused on understanding the role of defective N-glycosylation in CD, as an innovative strategy to identify and develop new therapeutics. Depending on ancestral background, 7-25% of CD patients carry a pathogenic, missense mutation in the manganese (Mn) transporter ZIP8 (rs13107325; ZIP8 A391T). ZIP8 regulates systemic Mn homeostasis with ZIP8 391-Thr causing a relative Mn insufficiency. Mn is a required metal cofactor for enzymes regulating key cellular processes, like N-glycosylation. In the gut, protein N-glycosylation plays key roles in host-pathogen interactions, inflammation, and cell-cell interactions. The investigator's central hypothesis is that in patients carrying ZIP8 391-Thr - CD is exacerbated by aberrant N-glycosylation and that this defect can be targeted by specific, safe therapy. Supporting this hypothesis, Mn levels are reduced (\~15%) in ZIP8 391-Thr allele carriers and this is associated with a decrease in complex N-glycan branching in plasma. Further, the investigators uncovered a microbiota signature in the ileal mucosa that implicated altered bile acid homeostasis in ZIP8 391-Thr carriers. To better understand CD in ZIP8 391 carriers, the investigators generated a knock-in mouse model of ZIP8 391-Thr (Zip8393T/393T). Like patient data, the investigators observe reduced branching of N-glycans and disrupted bile acid homeostasis in the Zip8393T/393T mice. Promising human trials have shown that defects in N-glycan branching can be safely restored by raising levels of the rate-limiting metabolite UDP-N-acetylglucosamine (GlcNAc) via supplementation with free GlcNAc. The investigator's preliminary data in Zip8393T/393T mice have demonstrated that GlcNAc supplementation restores N-glycan branching deficits, rescues the defect in bile acid homeostasis, and ameliorates colitis susceptibility. Thus, the objective of the proposed research is to test a safe and effective therapy for patients carrying ZIP8 391-Thr and others who may have underlying changes in N-glycosylation. The investigators will perform a multi-center, randomized, double-blind, placebo-controlled cross-over study to test the safety and tolerability of oral GlcNAc as a proof-of-concept study. The investigators will use two cohorts stratified by ZIP8 391-Thr genotype status (carriers and non-carriers, n= 20 participants in each cohort, total= 40 participants).

Key Dates

Start date
Jun 30, 2026
Status verified
May 2026
Primary completion
Jul 31, 2028
Completion
Dec 31, 2028

Study Design

Enrollment
40 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT

Arms

  • Experimental: Participants with Crohn's disease and carry ZIP8 391-Thr (heterozygous or homozygous carriers)
    N-acetylglucosamine
  • Experimental: Participants with Crohn's disease who do not carry ZIP8 391-Thr
    N-acetylglucosamine

Primary Outcome Measure

Safety and tolerability: Number of Crohn's disease exacerbations [ Time Frame: Weeks 0-6, Weeks 6-9, Weeks 9-15, Weeks 15-18 ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Johns Hopkins University School of MedicineBaltimoreMaryland21205
Joanna MP Melia, MD
[email protected]
410-502-1559
Lynn Kobeissi, MD
[email protected]

Find similar trials in Baltimore, MD

By condition
Crohn's disease
By specialty
GastroenterologyInflammatory bowel diseaseAutoimmune disease
By research site
Johns Hopkins University School of Medicine· Baltimore, MD

Related Studies