Crohns DiseasePhase 2NAGICNCT07225998
Oral N-acetylglucosamine in Crohn's Disease
A Phase 2 study testing N-Acetylglucosamine (GlcNAc) in people with Crohns Disease, run by Johns Hopkins University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Crohns Disease
- What is being tested?
- N-Acetylglucosamine (GlcNAc)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2027to 31 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 and 80 years of age
- Diagnosis of CD involving ileum (L1) or ileocolonic disease (L3) of any disease behavior
- On stable dosing of any CD therapy for >/= 8 weeks (inclusive of biologics, small molecules, immunomodulators)
- CDAI <450
- Willing to undergo genetic testing for ZIP8 genotype
- No steroids within the past 4 weeks
Show all 11Show fewer
- No antibiotics within the past 2 weeks
- 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 "highly effective" contraception throughout the study period and for 30 days after the last dose of study drug (all subjects of child-bearing potential)
Who cannot join
- Have taken GlcNAc or glucosamine in the previous 3 months
- Allergy to shellfish
- Severely-active CD defined as CDAI >450 AND/OR
- 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
- Steroids within the past 4 weeks
- Antibiotics within the past 2 weeks
Show all 20Show fewer
- Stricture with high-grade obstruction, significant fistulizing disease, presence of intra-abdominal or perianal abscess, perforation, or fulminant colitis requiring imminent surgical management
- Surgery within 12 weeks
- Recent initiation or escalation of immunosuppressive therapy (<8 weeks)
- 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
- 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, including primary sclerosing cholangitis
- History of seizure disorder
- Pregnant, less than 6 months postpartum, breastfeeding, or attempting to conceive
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21205
Joanna MP Melia, MD, 410-502-1559, jpeloqu2@jhmi.edu
Lynn Kobeissi, MD, lkobeis1@jh.edu
About this study
Official title: The NAGIC Study: Multi-center, Randomized, Double-blind, Placebo-controlled Cross-over Study of Oral N-acetylglucosamine in Ileal/Ileocolonic Crohn's Disease
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).
Read the 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 that showed promising results.
Key study information:
- The investigators will check if the participant carries the ZIP8 variant at study enrollment. The participants can choose to be informed of ZIP8 genetics.
- This is a randomized, double-blind, placebo-controlled, cross-over study. This study design provides the most power to determine if there is a beneficial effect of GlcNAc.
- This means the participant will receive the study drug (GlcNAc), but will also have a period of placebo. The sequence in which the participant receives the GlcNAc or placebo is randomized. The study is blinded, meaning that the participant and the investigator will not know if the participant is receiving active drug or placebo unless there are safety concerns.
- GlcNAc or placebo is provided to the participant as a powder that the participant will mix 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 18 weeks. 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. There are no direct costs to the participants.
- Conditions
- Crohns Disease
- Being tested
- N-Acetylglucosamine (GlcNAc)
- Keywords
- Crohns disease, manganese, GlcNAc, N-acetylglucosamine, ZIP8 protein, SLC39A8 gene, genetics, glycosylation disorder
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 group | Role | What they receive |
|---|---|---|
| Participants with Crohn's disease and carry ZIP8 391-Thr (heterozygous or homozygous carriers) | Experimental | N-acetylglucosamine Receives: Drug: N-Acetylglucosamine (GlcNAc) |
| Participants with Crohn's disease who do not carry ZIP8 391-Thr | Experimental | N-acetylglucosamine Receives: Drug: N-Acetylglucosamine (GlcNAc) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability: Number of Crohn's disease exacerbations
Safety and tolerability will be defined as freedom from Crohn's disease (CD) disease exacerbation. Number of CD exacerbations will be one composite outcome with exacerbation of CD activity defined as the occurrence of ANY of the following during each treatment phase:
- Crohn's disease activity index (CDAI) score (patient reported measure) change of >100 points, ii. initiation or change of CD therapy due to symptom worsening, iii. need for steroids related to CD disease activity, iv. CD-associated hospitalization, v. CD-associated surgery, vi. severe adverse events (CTCAE grade 3-5, attributed to CD disease activity, e.g. life-threatening perforation or sepsis)
Measured: Weeks 0-6, Weeks 6-9, Weeks 9-15, Weeks 15-18
Secondary outcomes (16)
Clinical response as assessed by CDAI score
Patient reported disease activity index: CDAI 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.
Clinical response will be defined as a ≥70 point reduction in CDAI score from baseline by the end of the six-week treatment period stratified by disease activity at week 0.
Measured: Week 6, week 15 for each treatment phase (GlcNAc and placebo)
Clinical response as assessed by mean change in CDAI score
Patient reported disease activity index: CDAI 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. Within-participant change from baseline in CDAI score stratified by disease activity at week 0.
Measured: Week 6, week 15 for each treatment phase (GlcNAc and placebo).
Clinical remission as assessed by CDAI score
Patient reported disease activity index: CDAI 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. Clinical remission will be defined as a CDAI score of <150 at the end of the six-week treatment period stratified by disease activity at week 0.
Measured: Week 6, week 15 for each treatment phase (GlcNAc and placebo).
Change in serum N-glycome
Measure of glycosylation Serum N-glycome (%): Change in Serum N-glycome from baseline to follow-up
Measured: Week 0, 6, 9, 15, 18
Change in saliva N-glycome
Measure of glycosylation: Change in saliva N-glycome (%) from baseline to follow-up.
Measured: Week 0, 6, 9, 15, 18
Mean change in serum UDP-GlcNAc
Measure of glycosylation: Serum UDP-GlcNAc (uM). Mean change in serum UDP-GlcNAc from baseline to follow-up.
Measured: Week 0, 6, 9, 15, 18
Change in T cell N-glycan branching
Measure of glycosylation: Change in T cell N-glycan branching (%) from baseline to follow-up
Measured: Week 0, 6, 9, 15, 18
Change in T cell activity/responsiveness
Measure of glycosylation: Change in T cell activity/responsiveness (%) from baseline to follow-up
Measured: Week 0, 6, 9, 15, 18
Change in fecal mucins
Measure of glycosylation: Change in fecal mucins (%) from baseline to follow-up
Measured: Week 0, 6, 9, 15, 18
Mean change in fecal calprotectin
Measure of inflammation. Mean change in fecal calprotectin (%) from baseline to follow-up
Measured: Week 0, 6, 9, 15, 18
Mean change in serum C-Reactive Protein (CRP)
Measure of inflammation: CRP (ng/ml) from baseline to follow-up
Measured: Week 0, 6, 9, 15, 18
Change in panel-based blood inflammatory cytokines
Measure of inflammation: Change in panel-based blood inflammatory cytokines (pg/ml) measures from baseline to follow-up.
Measured: Week 0, 6, 9, 15, 18
Change in marker of bile acid homeostasis (FGF19)
FGF19 is a circulating protein that is a marker of bile acid homeostasis.
Measured: Week 0, 6, 9, 15, 18
Mean change in sCD14
Measure of intestinal permeability sCD14 (pg/ml). Mean change in sCD14 from baseline to follow-up.
Measured: Week 0, 6, 9, 15, 18
Mean Change in FACIT-Fatigue Patient-reported measure (Fatigue)
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.
Measured: Week 0, 6, 9, 15, 18
Mean Change in Simple Ultrasound Activity (SUS-CD) Score Disease activity measured by intestinal ultrasound
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.
Measured: Week 0, 6, 9, 15, 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2025
- Study start5 Jan 2027 (estimated)
- Primary completion31 Jul 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Crohns DiseaseStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Leona M. & Harry B. Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Joanna Melia, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07225998
- Sponsor's protocol ID
- IRB00533883
- Other IDs
- R01DK141870, 2604-09127
- Acronym
- NAGIC
- Status last verified
- Nov 2026
- First submitted
- 29 Oct 2025
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) (data collected for each person, including demographics, Crohn's disease history, lab results, adverse events) will be shared after publication of results for research collaborations. IPD will be shared as a deidentified dataset with no protected health information (PHI) as per Institutional Review Board (IRB) regulations. Data sharing agreement will be required.
Publications
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.
PubMed 11121904Tomar V, Kang SD, 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. 2026 Jan 15;7(1):100517. doi: 10.1016/j.xhgg.2025.100517. Epub 2025 Sep 16.
PubMed 40963256
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The NAGIC Study: Multi-center, Randomized, Double-blind, Placebo-controlled Cross-over Study of Oral N-acetylglucosamine in Ileal/Ileocolonic Crohn's Disease
- ClinicalTrials.gov ID
- NCT07225998
- Acronym / sponsor ID
- NAGIC / IRB00533883
- Conditions
- Crohns Disease
- Keywords
- Crohns disease, manganese, GlcNAc, N-acetylglucosamine, ZIP8 protein, SLC39A8 gene, genetics, glycosylation disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Leona M. & Harry B. Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 5 Jan 2027 (estimated)
- Primary completion
- 31 Jul 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 10 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 that showed promising results.
Key study information:
- The investigators will check if the participant carries the ZIP8 variant at study enrollment. The participants can choose to be informed of ZIP8 genetics.
- This is a randomized, double-blind, placebo-controlled, cross-over study. This study design provides the most power to determine if there is a beneficial effect of GlcNAc.
- This means the participant will receive the study drug (GlcNAc), but will also have a period of placebo. The sequence in which the participant receives the GlcNAc or placebo is randomized. The study is blinded, meaning that the participant and the investigator will not know if the participant is receiving active drug or placebo unless there are safety concerns.
- GlcNAc or placebo is provided to the participant as a powder that the participant will mix 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 18 weeks. 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. There are no direct costs to the participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants with Crohn's disease and carry ZIP8 391-Thr (heterozygous or homozygous carriers) | Experimental | Drug: N-Acetylglucosamine (GlcNAc)N-acetylglucosamine |
| Participants with Crohn's disease who do not carry ZIP8 391-Thr | Experimental | Drug: N-Acetylglucosamine (GlcNAc)N-acetylglucosamine |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18 and 80 years of age
- Diagnosis of CD involving ileum (L1) or ileocolonic disease (L3) of any disease behavior
- On stable dosing of any CD therapy for >/= 8 weeks (inclusive of biologics, small molecules, immunomodulators)
- CDAI <450
- Willing to undergo genetic testing for ZIP8 genotype
Key exclusion criteria (20 listed)
- Have taken GlcNAc or glucosamine in the previous 3 months
- Allergy to shellfish
- Severely-active CD defined as CDAI >450 AND/OR
- 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
- Steroids within the past 4 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-Acetylglucosamine (GlcNAc)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. | Drug | Participants with Crohn's disease and carry ZIP8 391-Thr (heterozygous or homozygous carriers), Participants with Crohn's disease who do not carry ZIP8 391-Thr |
Primary outcome
Safety and tolerability: Number of Crohn's disease exacerbations
Time frame: Weeks 0-6, Weeks 6-9, Weeks 9-15, Weeks 15-18
Safety and tolerability will be defined as freedom from Crohn's disease (CD) disease exacerbation. Number of CD exacerbations will be one composite outcome with exacerbation of CD activity defined as the occurrence of ANY of the following during each treatment phase: i. Crohn's disease activity index (CDAI) score (patient reported measure) change of >100 points, ii. initiation or change of CD therapy due to symptom worsening, iii. need for steroids related to CD disease activity, iv. CD-associated hospitalization, v. CD-associated surgery, vi. severe adverse events (CTCAE grade 3-5, attributed to CD disease activity, e.g. life-threatening perforation or sepsis)
16 secondary outcomes
Clinical response as assessed by CDAI score
Time frame: Week 6, week 15 for each treatment phase (GlcNAc and placebo)
Clinical response as assessed by mean change in CDAI score
Time frame: Week 6, week 15 for each treatment phase (GlcNAc and placebo).
Clinical remission as assessed by CDAI score
Time frame: Week 6, week 15 for each treatment phase (GlcNAc and placebo).
Change in serum N-glycome
Time frame: Week 0, 6, 9, 15, 18
Change in saliva N-glycome
Time frame: Week 0, 6, 9, 15, 18
Mean change in serum UDP-GlcNAc
Time frame: Week 0, 6, 9, 15, 18
Change in T cell N-glycan branching
Time frame: Week 0, 6, 9, 15, 18
Change in T cell activity/responsiveness
Time frame: Week 0, 6, 9, 15, 18
Change in fecal mucins
Time frame: Week 0, 6, 9, 15, 18
Mean change in fecal calprotectin
Time frame: Week 0, 6, 9, 15, 18
Mean change in serum C-Reactive Protein (CRP)
Time frame: Week 0, 6, 9, 15, 18
Change in panel-based blood inflammatory cytokines
Time frame: Week 0, 6, 9, 15, 18
Change in marker of bile acid homeostasis (FGF19)
Time frame: Week 0, 6, 9, 15, 18
Mean change in sCD14
Time frame: Week 0, 6, 9, 15, 18
Mean Change in FACIT-Fatigue Patient-reported measure (Fatigue)
Time frame: Week 0, 6, 9, 15, 18
Mean Change in Simple Ultrasound Activity (SUS-CD) Score Disease activity measured by intestinal ultrasound
Time frame: Week 0, 6, 9, 15, 18
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Background: PubMed 11121904Salvatore 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.
- Background: PubMed 40963256Tomar V, Kang SD, 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. 2026 Jan 15;7(1):100517. doi: 10.1016/j.xhgg.2025.100517. Epub 2025 Sep 16.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) (data collected for each person, including demographics, Crohn's disease history, lab results, adverse events) will be shared after publication of results for research collaborations. IPD will be shared as a deidentified dataset with no protected health information (PHI) as per Institutional Review Board (IRB) regulations. Data sharing agreement will be required.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joanna Melia, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-Acetylglucosamine (GlcNAc) in people with Crohns Disease, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joanna MP Melia, MD (410-502-1559, jpeloqu2@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07225998, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.