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Noninvasive Diagnosis of Hypolactasia With 4-Galactosylxylose (Gaxilose): A Multicentre, Open-Label, Phase IIB-III Nonrandomized Trial

Aragón, Juan J. MD, PhD*; Hermida, Carmen PhD*,†; Martínez-Costa, Oscar H. MD, PhD*; Sánchez, Valentina BD*; Martín, Igor BD; Sánchez, José J. MD, PhD§; Codoceo, Rosa MD, PhD; Cano, José M. MD, PhD; Cano, Ana MD, PhD#; Crespo, Laura MD#; Torres, Yolanda MD**; García, Francisco J. MD**; Fernández-Mayoralas, Alfonso PhD††; Solera, Jesús MD, PhD‡‡; Martínez, Pilar PhD‡‡

Journal of Clinical Gastroenterology: January 2014 - Volume 48 - Issue 1 - p 29–36
doi: 10.1097/MCG.0b013e318297fb10
ALIMENTARY TRACT: Original Articles

Goals and Background: 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).

Study: 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.

*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

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Presented in part at the Semana de las Enfermedades Digestivas, June 2–5, 2012, Bilbao, Spain; and at the 20th United European Gastroenterology Week, October 20–24, 2012, Amsterdam, The Netherlands.

The study was registered, number EudraCT: 2006-002793-21 (http://www.clinicaltrialsregister.eu).

Supported by Ministerio de Ciencia e Innovación, Spain (grants BFU2008-02364 and BFU2009-13114 to J.J.A.), Comunidad Autónoma de Madrid, Spain (grant S2009/PPQ-1752 to A.F.-M.), and Venter Pharma SL (Madrid, Spain).

C.H. is an employee of Venter Pharma SL (Madrid, Spain); J.J.A. and A.F-M. are shareholders of Venter Pharma SL. The remaining authors declare that they have nothing to disclose.

Reprints: Juan J. Aragón, MD, PhD, Departamento de Bioquímica, Facultad de Medicina de la Universidad Autónoma de Madrid, Arzobispo Morcillo 4, Madrid 28029, Spain (e-mail: juanjose.aragon@uam.es).

Received November 13, 2012

Accepted April 18, 2013

© 2014 by Lippincott Williams & Wilkins