Several pathophysiological mechanisms have been proposed in functional gastrointestinal (GI) disorders, e.g. altered GI motility and sensitivity. The aim of this study was to investigate gastric electrical activity (GEA) in patients with functional dyspepsia (FD) or irritable bowel syndrome (IBS) compared with healthy controls (HC), and to assess if abdominal symptoms and delayed gastric emptying are associated with alterations in GEA, as determined by electrogastrography (EGG). Forty patients with FD, IBS or both were compared with 22 HC. EGG was performed before and after a standard meal. Frequencies and amplitudes pre- and post-prandially were analysed. Furthermore, gastric emptying and symptom scores were assessed. Eight of 40 patients (20%; three FD, three IBS, two FD and IBS) had delayed gastric emptying. Disturbed gastric emptying and lack of a postprandial increase in the EGG amplitude were significantly correlated (r = 0.8; P < 0.005). No differences between controls and patients were observed in the distribution of EGG frequencies. Treatment with the prokinetically active macrolide erythromycin improved gastric emptying, GEA and symptoms (n = 4). The data suggest that EGG could be useful as a diagnostic tool in patients with FD and IBS to identify a subgroup of patients with delayed gastric emptying.
BackgroundA modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid‐A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short‐course treatment of grass‐pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial.MethodsIn this exploratory, randomized, double‐blind, placebo‐controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre‐seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18–65 years) with moderate‐to‐severe SAR with or without asthma that was well‐controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ‐S) and allergen‐specific IgG4 response.ResultsThe mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ‐S for the extended regimen (mean change −0.72, p = .02). Both regimens were well‐tolerated.ConclusionsThis trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well‐tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.
RATIONALE: This exploratory field study explores the safety and efficacy of an optimized dose of a modified grass allergen subcutaneous immunotherapy (SCIT) product (1.0 ml) with microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL) adjuvant system for the treatment of allergic rhinoconjunctivitis (ARC) due to grass pollen. METHODS: This multi-center, randomised, double-blind, placebocontrolled, parallel-group exploratory field study is conducted in approximately 150 subjects in Europe and the US. Subjects are randomized to six pre-seasonal subcutaneous injections of active treatment or placebo in a 2:1 ratio. The primary endpoint is the combined symptom and medications score (CSMS) during the peak grass pollen season. RESULTS: The subject population included in this study will be presented by baseline characteristics (e.g. country, age and gender). The study design applies two frequently used primary endpoint scores: the CSMS and the Total Combined Score (TCS). As this study also includes conjunctival provocation testing (CPT), this study allows the evaluation of the relationship between CPT, CSMS and TCS. In addition, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) will be evaluated and the extensive panel of biomarkers applied will be presented. CONCLUSIONS: This stepwise clinical development approach is novel in allergen immunotherapy. The results of this exploratory field study will dictate the optimal design of the pivotal Phase III study. The completion of the recruitment of this exploratory field study is an important achievement in the development of an efficacious and safe state-of-the-art grass SCIT product to be developed for the European and the US markets.
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