4-o-galactopyranosylxylose and Lactose-Intolerance

The diagnostic accuracy of the Gaxilose test (GT) for hypolactasia diagnosis has already been proved. The objectives of this clinical trial were to demonstrate the noninferiority of the GT compared to the hydrogen breath test (HBT) on the impact on diagnostic thinking and patient management, to evaluate the GT reproducibility with urine accumulated from 0 to 4 hours and from 0 to 5 hours and to assess test safety.. We conducted a randomized, parallel, noninferiority clinical trial. Patients with clinical symptoms suggestive of lactose intolerance were screened for inclusion and randomly assigned to the GT arm or the HBT arm of the study. The impact on diagnostic thinking and patient management was analyzed with pretest and posttest questionnaires in which the investigators indicated their estimated probability of hypolactasia diagnosis and the intended management before and after the GT or the HBT (noninferiority margin: -10%). The primary outcome of the study was the impact on diagnostic thinking, expressed as the mean of the absolute values of the differences between the pretest and posttest probabilities of hypolactasia diagnosis. Patients randomized to the GT arm performed also the retest to evaluate the reproducibility of the GT.. A total of 147 patients were included in the intend-to-treat (ITT) population. Among them, 74 performed the HBT and 73 performed the GT. The results proved the noninferiority of the GT compared to the HBT on the impact on diagnostic thinking (ImpactGT = 31.74 ± 23.30%; ImpactHBT = 24.28 ± 19.87%; ΔGT-HBT = 7.46%; 95% confidence interval of ΔGT-HBT: 1.55%, infinite) and on patient management. The test-retest reproducibility was better for the GT with urine accumulated from 0 to 5 h: the intraclass correlation coefficient (ICC) was 0.5761, and the Kappa coefficient was 0.7548, indicative of substantial agreement between both tests. No serious adverse events were reported during the study.. The GT has an impact on diagnostic thinking and patient management noninferior to that of the HBT, is reproducible and well tolerated. These results prove the clinical benefit of its use in the clinical practice (ClinicalTrials.gov identifier: NCT02636413).

Topics: Adult; Aged; Breath Tests; Decision Making; Disaccharides; Female; Humans; Hydrogen; Intention to Treat Analysis; Lactose Intolerance; Male; Middle Aged; Reproducibility of Results; Xylose

Hypolactasia affects over half of the world population. Diagnosis remains problematic as currently available tests, such as the hydrogen breath test, have low reliability and lactose intolerance symptoms are unspecific. We evaluated the diagnostic performance and safety of a new noninvasive diagnostic test based on urine or serum measurement of D-xylose after lactase cleavage of orally administered 4-galactosylxylose (gaxilose).. In a multicentre, open-label, nonrandomized, phase IIb-III study, consecutive patients with symptoms suggestive of lactose intolerance sequentially underwent intestinal biopsy for direct measurement of lactase activity (reference standard), hydrogen breath test, and blood glucose test after lactose challenge, 4- and 5-hour urine-based gaxilose test, and blood-based gaxilose test. For the gaxilose tests, 0 to 4 and 4 to 5 hours urine samples were taken after a 0.45 g gaxilose dose, whereas serum samples were taken 90 minutes after a 2.7 g dose for D-xylose determination. Genetic testing of hypolactasia was also assessed.. Of the 222 patients enrolled, 203 completed all diagnostic tests; 108 were hypolactasic according to biopsy. The sensitivities and specificities and positive and negative predictive values of the gaxilose tests were all >90% versus 69% to 85% for the hydrogen breath test and the blood glucose test. The area under the ROC curve was significantly higher for the gaxilose tests (>0.9, P≤0.007). These tests also had higher sensitivity than genetic testing for hypolactasia and were well tolerated.. The diagnostic performance of the gaxilose tests is excellent and can substantially improve the diagnosis of hypolactasia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Blood Glucose; Breath Tests; Disaccharides; Female; Genetic Testing; Humans; Lactase; Lactose Intolerance; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Time Factors; Xylose; Young Adult

Hypolactasia is widespread, yet reliable diagnostic tests are lacking. A new test based on oral administration of 4-galactosylxylose (gaxilose) and urine or serum measurement of D-xylose after cleavage by intestinal lactase is under clinical development. We investigated the optimal dose of gaxilose and calculate cutoff values of D-xylose for that dose.. In the randomized, dose-finding, phase I study, urine and serum pharmacokinetics of D-xylose were determined after oral administration of 6 ascending doses of gaxilose (and placebo) to 12 healthy adult volunteers. In the open, parallel, phase Ib study, 30 volunteers received the doses established for the urine and blood tests and D-xylose was measured. Cutoff values were calculated as 1.96 × SD below the mean value. Safety was assessed through reporting of adverse events.. Gaxilose administration showed a progressive, dose-dependent increase in D-xylose in urine and serum. An optimal gaxilose dose of 0.45 g and urine collection periods of 4 and 5 hours were selected for further studies. For the blood test, a 2.7 g dose was selected and C max measured at 90 minutes. The calculated cutoff values of D-xylose for normal lactase activity were 27.58 and 37.87 mg for the 4- and 5-hour urine tests, respectively, and 0.97 mg/dL for the blood test. There were no treatment-related adverse events.. The methodology described provides a simple, safe test for the evaluation of lactase activity in vivo. Further evaluation of the test as a noninvasive diagnosis of hypolactasia is ongoing in patients with lactose intolerance.

Topics: Adult; Disaccharides; Female; Humans; Intestines; Lactase; Lactose Intolerance; Male; Single-Blind Method; Xylose

Lactose intolerance is a pathology caused by lactase enzyme deficiency, usually produced in the intestinal cells provoking symptoms as abdominal pain, bloating, diarrhea, gas and nausea. Gaxilose, 4-O-β-D galactopyranosyl-d-xylose, is used as a diagnostic drug for a non-invasive method for hypolactasia diagnosis. To date, no definitive guide for identifying gaxilose and distinguishing between crystalline forms is available. Data have been collected from a number of different analytical techniques in order to provide a full characterization of the compound and a simple method to discriminate between two solid forms.

Topics: Abdominal Pain; Carbohydrate Conformation; Crystallization; Diarrhea; Disaccharides; Humans; Lactose Intolerance; Nausea; Powder Diffraction

There is no consensus on the most accurate method to diagnose primary hypolactasia. We aimed to compare the diagnostic accuracy of the new gaxilose test with 2 traditional tests (lactose tolerance test and clinical criteria) for the diagnosis of primary hypolactasia using the C/T-13910 polymorphism as a reference standard.. Patients with a clinical suspicion of lactose intolerance were subjected to gaxilose tests, shortened lactose tolerance tests, and symptom questionnaires before and after overload with 50 g lactose and after a lactose-free diet. The diagnostic accuracy and degree of agreement and correlation were assessed using a genetic test (C/T-13910 polymorphism) as a reference standard and their respective 95% confidence intervals.. Thirty consecutive patients (70% women) participated in the study. The genetic test confirmed the C/T-13910 polymorphism in 11 patients (36.8%). The presence of diarrhoea and the symptom score after lactose overload, along with the tolerance test, were the variables with the highest degree of agreement (κ > 0.60). Area under the ROC curve was >0.82 (p < 0.05), with sensitivity and specificity values of >0.80. However, the gaxilose test obtained lower values: κ, 0.47; area under curve, 0.75 (0.57-0.94); sensitivity, 0.82 (0.55-1); and specificity, 0.68 (0.45-0.92). The multivariate analysis showed an association between the post-overload symptom questionnaire and the results of the genetic test (odds ratio: 1.17; 1.04-1.31; p < 0.01).. The presence of diarrhoea and the symptom score after overload with 50 g lactose showed a higher degree of agreement and diagnostic accuracy for primary hypolactasia than the gaxilose test when the genetic test is used as a reference standard.

Topics: Adult; Colorimetry; Disaccharides; Female; Genetic Testing; Humans; Lactase; Lactose; Lactose Intolerance; Lactose Tolerance Test; Male; Middle Aged; Non-Randomized Controlled Trials as Topic; Polymorphism, Single Nucleotide; Prospective Studies; Sensitivity and Specificity; Surveys and Questionnaires; Young Adult