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Not yet recruitingPhase 2

Oral N-acetylglucosamine in Crohn's Disease

The NAGIC Study: Multi-center, Randomized, Double-blind, Placebo-controlled Cross-over Study of Oral N-acetylglucosamine in Ileal/Ileocolonic Crohn's Disease

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 80 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Ultrasound

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "There are brief, weekly check-ins and 7-8 in-person visits. * Participants will be asked to provide blood, stool, and saliva samples for a total of 7-8 times. * If it is possible at the participant's site, intestinal ultrasounds will be performed over the course of the study. * Participants will be paid to participate in the study."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety of N-acetylglucosamine (GlcNAc), taken by mouth, and how well people can tolerate it. It is for adults with Crohn’s disease affecting the last part of the small intestine, with or without the large intestine. The study compares GlcNAc with a placebo, which has no active study drug.

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).

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 18 to 80 years old.
  • Have Crohn’s disease in the last part of the small intestine, with or without disease in the large intestine.
  • Have a Crohn’s Disease Activity Index (CDAI) score below 450. This score measures symptoms.
  • Have been on a steady dose of Crohn’s medicine for at least 8 weeks.
  • Have used no steroids in the past 4 weeks and no antibiotics in the past 2 weeks.
  • Agree to testing for the ZIP8 gene and give informed consent to join.
  • Agree to all home and clinic follow-up visits and share your latest bowel scope and imaging results, plus past tissue samples when possible.
  • If you can become pregnant, agree to use highly effective birth control during the study and for 30 days after the last dose.

Who can't join

  • Used GlcNAc or glucosamine in the past 3 months, or have a shellfish allergy.
  • Have severe Crohn’s disease: a CDAI score above 450, or a recent bowel scope score of at least 16 (at least 8 if only the last part of the small intestine is affected).
  • Have serious bowel problems, such as a major blockage, abnormal tunnels between tissues, pockets of infection in the belly or near the anus, a bowel hole, or severe inflammation needing urgent surgery.
  • Used steroids in the past 4 weeks or antibiotics in the past 2 weeks; had surgery within 12 weeks; or started or increased medicine that weakens the immune system within 8 weeks.
  • Have important abnormal blood test results, including high white blood cells, very low hemoglobin, high liver tests, reduced kidney function, or low iron stores.
  • Have type 1 diabetes, type 2 diabetes treated with insulin, or type 2 diabetes with an HbA1c above 6.5%, a measure of blood sugar over time.
  • Have a history of blood vessel disease, heart artery disease, stroke or mini-stroke, cancer, organ transplant, bleeding disorder, long-term breathing disease including asthma, kidney failure, long-term liver disease, or seizures.
  • Are pregnant, gave birth less than 6 months ago, are breastfeeding, or are trying to become pregnant.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: 1. Age 18 and 80 years of age 2. Diagnosis of CD involving ileum (L1) or ileocolonic disease (L3) of any disease behavior 3. On stable dosing of any CD therapy for \>/= 8 weeks (inclusive of biologics, small molecules, immunomodulators) 4. CDAI \<450 5. Willing to undergo genetic testing for ZIP8 genotype 6. No steroids within the past 4 weeks 7. No antibiotics within the past 2 weeks 8. Willing to provide informed consent 9. Willing to participate in all at-home and clinic-based follow-up 10. Willing to provide most recent endoscopy and imaging results; when possible, access to prior pathology specimens 11. Willing to use all forms of "highly effective" contraception throughout the study period and for 30 days after the last dose of study drug (all subjects of child-bearing potential) Exclusion criteria 1. Have taken GlcNAc or glucosamine in the previous 3 months 2. Allergy to shellfish 3. Severely-active CD defined as CDAI \>450 AND/OR 4. Simple Endoscopic Score for Crohn's Disease (SES-CD) score \>/= 16 (or \>/= 8 for isolated ileitis) on colonoscopy within 8 weeks of screening, if available 5. Steroids within the past 4 weeks 6. Antibiotics within the past 2 weeks 7. Stricture with high-grade obstruction, significant fistulizing disease, presence of intra-abdominal or perianal abscess, perforation, or fulminant colitis requiring imminent surgical management 8. Surgery within 12 weeks 9. Recent initiation or escalation of immunosuppressive therapy (\<8 weeks) 10. Any clinically significant abnormalities on routine clinical labs, including unexplained white blood cells (WBC) \>16,000, hemoglobin \<7, AST/ALT \>2x ULN, alkaline phosphatase \>2x ULN, eGFR \<60, ferritin \<30 ng/ml2 11. History of type 1 diabetes, inadequately controlled type 2 diabetes (HbA1c\>6.5%), type 2 diabetes on insulin 12. History of peripheral vascular disease, coronary artery disease, stroke, transient ischemic attack 13. History of cancer 14. History of organ transplant 15. History of bleeding disorder 16. History of chronic respiratory disorder, including asthma 17. History of chronic renal failure 18. History of chronic liver disease, including primary sclerosing cholangitis 19. History of seizure disorder 20. Pregnant, less than 6 months postpartum, breastfeeding, or attempting to conceive

Study sites (1)

MD