title: Noninvasive diagnosis of hypolactasia with 4-Galactosylxylose (Gaxilose): a multicentre, open-label, phase IIB-III nonrandomized trial.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The diagnostic performance of the gaxilose tests is excellent and can substantially improve the diagnosis of hypolactasia.
authors.affiliation: *Departamento de Bioquímica and Instituto de Investigaciones Biomédicas Alberto Sols Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas, Facultad de Medicina, Universidad Autónoma de Madrid †Venter Pharma SL ‡Departamento de Estadística, Chiltern International Spain SA §Departamento de Medicina Preventiva y Salud Pública y Microbiología, Facultad de Medicina de la Universidad Autónoma de Madrid ∥Servicio de Bioquímica, Sección de Gastroenterología y Nutrición ¶Servicio de Digestivo, Hospital Universitario La Paz #Servicio de Digestivo, Hospital Universitario Ramón y Cajal ††Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas ‡‡Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid **Servicio de Digestivo, Hospital San Juan de Dios de Aljarafe, Sevilla, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Aragón
authors.forename: Carmen
authors.initials: C
authors.lastname: Hermida
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Martínez-Costa
authors.forename: Valentina
authors.initials: V
authors.lastname: Sánchez
authors.forename: Igor
authors.initials: I
authors.lastname: Martín
authors.forename: José J
authors.initials: JJ
authors.lastname: Sánchez
authors.forename: Rosa
authors.initials: R
authors.lastname: Codoceo
authors.forename: José M
authors.initials: JM
authors.lastname: Cano
authors.forename: Ana
authors.initials: A
authors.lastname: Cano
authors.forename: Laura
authors.initials: L
authors.lastname: Crespo
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Torres
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: García
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernández-Mayoralas
authors.forename: Jesús
authors.initials: J
authors.lastname: Solera
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D001944:Breath Tests / Q000379:methods; D004187:Disaccharides / Q000008:administration & dosage; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D043322:Lactase / Q000378:metabolism*; D007787:Lactose Intolerance / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors; D014994:Xylose / Q000097:blood / Q000378:metabolism* / Q000652:urine; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004187:Disaccharides; C073827:4-O-galactopyranosylxylose; D014994:Xylose; D043322:Lactase