The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study.
Aliment Pharmacol Ther
; 26(5): 757-66, 2007 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-17697209
ABSTRACT
BACKGROUND:
Lifelong adherence to a strict gluten-free diet is the cornerstone of coeliac disease treatment. Elucidation of disease pathogenesis has created opportunities for novel therapeutic approaches to coeliac disease. AT-1001 is an inhibitor of paracellular permeability whose structure is derived from a protein secreted by Vibrio cholerae.AIM:
To determine the safety and tolerability of 12 mg doses of AT-1001 in coeliac disease subjects challenged with gluten.METHODS:
An in-patient, double-blind, randomized placebo-controlled safety study utilizing intestinal permeability, measured via fractional excretions of lactulose and mannitol, as an exploratory measure of drug efficacy.RESULTS:
Compared to placebo, no increase in adverse events occurred in patients exposed to AT-1001. Following acute gluten exposure, a 70% increase in intestinal permeability was detected in the placebo group, while none was seen in the AT-1001 group. Interferon-gamma levels increased in four of seven patients (57%) of the placebo group, but only in four of 14 patients (29%) of the AT-1001 group. Gastrointestinal symptoms were more frequently detected in the placebo group when compared to the AT-1001 group (P = 0.018).CONCLUSIONS:
AT-1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad Celíaca
/
Receptores de Superficie Celular
/
Glútenes
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Aliment Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
GASTROENTEROLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos