Evaluation of LacTEST (gaxilose) Oral Solution 0.45 g as a Non‑invasive Marker of Intestinal Barrier Integrity and Permeability in Patients with Celiac Disease

Primary objective: evaluate whether the oral diagnostic agent LacTEST 0.45 g can serve as a surrogate marker of histological integrity of the small‑intestinal mucosa and of intestinal permeability in patients with celiac disease, providing a non‑invasive tool for monitoring mucosal recovery during a gluten‑free diet.

Secondary objectives:

• Determine the correlation between tissue‑level lactase activity and urinary xylose excretion 5 hours after LacTEST administration at baseline and after 12 months of gluten‑free diet.
• Determine the correlation between tissue lactase activity (urinary xylose) and intestinal permeability measured by lactulose/mannitol ratio, serum lipopolysaccharide‑binding protein, soluble CD14, and stool zonulin at baseline, 6 months, and 12 months.
• Determine the correlation between Marsh‑Oberhuber histological grading and changes in permeability parameters (lactulose/mannitol, LBP, sCD14, zonulin) at baseline and 12 months.
• Assess the influence of dietary compliance on intestinal atrophy, lactase activity, permeability markers, and symptom severity by measuring stool gluten immunogenic peptides at baseline, 6 months, and 12 months.
• Correlate all analytical parameters with patient‑reported symptoms at each study visit.
• Characterize γδ T‑cell subpopulations in fresh mucosal tissue and evaluate their association with epithelial recovery and the analytical parameters studied.
• Investigate polymorphisms of the persistent lactase gene and their relationship with the analytical parameters studied.

The trial enrolled adult individuals of both sexes, aged 18 to 70 years, who were identified as having suspected celiac disease based on compatible clinical presentation, positive anti‑tissue transglutaminase antibodies, and the presence of HLA‑DQ2 and/or HLA‑DQ8 haplotypes; participants were required to demonstrate capacity to understand the study and provide informed consent. The sponsor did not provide the total number of participants, and no specific lifestyle restrictions or requirements were detailed in the available information.

The interventional Phase IV study enrolls adults 18–70 years with suspected celiac disease who present compatible symptoms, positive anti‑tissue transglutaminase antibodies, and HLA‑DQ2/DQ8 haplotypes; participants must provide informed consent. Recruitment commences on 4 May 2026 and concludes on 4 May 2027, with each subject remaining in the protocol for approximately 12 months following initiation of a gluten‑free diet (GFD). After a screening visit to verify inclusion criteria, a baseline visit is performed in which the test product LacTEST 0.45 g is administered orally and urine is collected five hours later for xylose quantification; concurrent blood sampling, intestinal biopsy for Marsh‑Oberhuber classification, and other biomarker assessments are obtained. Follow‑up visits occur at 6 months and 12 months, repeating the LacTEST administration, urine collection, blood tests, and, at the final visit, a repeat biopsy. Primary endpoints—change in Marsh‑Oberhuber classification, intestinal lactase activity, and urinary xylose excretion—are evaluated at the 12‑month visit, while secondary endpoints (including anti‑TG antibody levels, lactulose/mannitol test results, LBP, sCD14, zonulin, symptom questionnaires, γδT‑cell percentages, MCM6 genotypes, and exploratory cytokine measurements) are assessed at both 6‑ and 12‑month time points. The study duration for each participant is therefore 12 months, encompassing screening, baseline, two interim assessments, and an end‑of‑study visit.

The investigational product, LacTEST 0.45 g powder for oral solution, is a diagnostic agent containing the active substance gaxilose. Each administered dose consists of 0.45 g of the powder, which is reconstituted according to the manufacturer’s instructions to form an oral solution. The solution is administered by the oral route, typically as a single dose per study visit, with the exact timing aligned to the study schedule. The pharmaceutical form is classified as an oral solution, and the product is identified by the ATC code V04CX (other diagnostic agents).

No comparator drug, placebo, or additional investigational therapy is employed in this study. Participants continue any standard-of-care management for celiac disease as prescribed by their treating physicians, but these treatments are not part of the trial protocol and are not administered under study conditions.

Administration of LacTEST is performed under direct observation to ensure compliance, with study staff documenting the exact time of ingestion and confirming complete consumption of the reconstituted solution. Any deviations from the dosing schedule are recorded in the case report form, and participants are instructed to refrain from eating or drinking for a specified interval before and after the test to maintain consistency of the measurement.

Efficacy will be evaluated using a set of predefined primary and secondary endpoints measured at baseline, 6 months, and 12 months after initiation of a gluten‑free diet. The primary endpoints include change in Marsh‑Oberhuber classification, change in intestinal lactase activity (µmol disaccharide/min/g tissue) assessed by direct measurement, and change in Xylose excreted (mg) in urine collected 5 hours after ingestion of LacTEST 0.45 g.

Secondary efficacy parameters comprise repeated assessments of the same lactase activity and xylose excretion at 6 months, as well as changes in antitransglutaminase antibodies (IU/L, mg/dL or g/L) measured in blood, L/M tests (% recovery of lactulose and mannitol and LMR), LBP (µg/mL), sCD14 (ng/mL), and zonulin (ng/L) in stool. Additional secondary measures include quantification of gluten immunogenic peptides (GIPs, µg/g) in stool, genotype analysis of MCM6 polymorphisms, and evaluation of γδ T‑cell subpopulations in intestinal tissue.

Clinical outcomes will be captured using validated questionnaires administered at each visit: the Gastrointestinal Symptom Rating Scale (GSRS), the Canadian Celiac Health Survey, the Celiac Disease Quality of Life questionnaire (CD‑QOL), and the Celiac Dietary Adherence Test (CDAT). Exploratory endpoints involve measurement of selected inflammatory cytokines in blood.

All laboratory assessments will be performed using standard analytical methods appropriate for each biomarker. Urine samples for xylose excretion will be collected 5 hours post‑dose, blood draws for antibodies and cytokines will follow routine phlebotomy protocols, and stool samples will be processed for zonulin and GIP analysis. Histological evaluation of the duodenal mucosa will be conducted by blinded pathology review according to the Marsh‑Oberhuber criteria. Data will be analyzed by comparing baseline values with those obtained at the scheduled follow‑up visits, using appropriate statistical methods for repeated measures.