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Low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet compared with traditional dietary advice for diarrhea-predominant irritable bowel syndrome: a parallel-group, randomized controlled trial with analysis of clinical and microbiological factors associated with patient outcomes.
Zhang, Y, Feng, L, Wang, X, Fox, M, Luo, L, Du, L, Chen, B, Chen, X, He, H, Zhu, S, et al
The American journal of clinical nutrition. 2021;(6):1531-1545
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Abstract
BACKGROUND The efficacy and factors associated with patient outcomes for a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) compared with traditional dietary advice (TDA) based on modified National Institute for Clinical Excellence guidelines for irritable bowel syndrome with diarrhea (IBS-D) in regions consuming a non-Western diet are unclear. OBJECTIVES We aimed to determine the efficacy of an LFD compared with TDA for the treatment of IBS-D in Chinese patients and to investigate the factors associated with favorable outcomes. METHODS One hundred and eight Chinese IBS-D patients (Rome III criteria) were randomly assigned to an LFD or TDA. The primary endpoint was a ≥50-point reduction in the IBS Severity Scoring System at 3 wk. Fecal samples collected before and after the dietary intervention were assessed for changes in SCFAs and microbiota profiles. A logistic regression model was used to identify predictors of outcomes. RESULTS Among the 100 patients who completed the study, the primary endpoint was met in a similar number of LFD (30 of 51, 59%) and TDA (26 of 49, 53%) patients (∆6%; 95% CI: -13%, 24%). Patients in the LFD group achieved earlier symptomatic improvement in stool frequency and excessive wind than those following TDA. LFD reduced carbohydrate-fermenting bacteria such as Bifidobacterium and Bacteroides, and decreased saccharolytic fermentation activity. This was associated with symptomatic improvement in the responders. High saccharolytic fermentation activity at baseline was associated with a higher symptom burden (P = 0.01) and a favorable therapeutic response to the LFD (log OR: 4.9; 95% CI: -0.1, 9.9; P = 0.05). CONCLUSIONS An LFD and TDA each reduced symptoms in Chinese IBS-D patients; however, the LFD achieved earlier symptomatic improvements in stool frequency and excessive wind. The therapeutic effect of the LFD was associated with changes in the fecal microbiota and the fecal fermentation index. At baseline, the presence of severe symptoms and microbial metabolic dysbiosis characterized by high saccharolytic capability predicted favorable outcomes to LFD intervention.This trial was registered at clinicaltrials.gov as NCT03304041.
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Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome.
Weickert, MO, Kaltsas, G, Hörsch, D, Lapuerta, P, Pavel, M, Valle, JW, Caplin, ME, Bergsland, E, Kunz, PL, Anthony, LB, et al
Clinical therapeutics. 2018;(6):952-962.e2
Abstract
PURPOSE In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival. METHODS Assessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan. FINDINGS In 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status. IMPLICATIONS Up to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors. ClinicalTrials.gov identifier: NCT01677910.