Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various ap-proaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting.
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PMID:Placebo effect in clinical trial design for irritable bowel syndrome. 2484 Mar 69

Fatigue is the most common extraintestinal symptom in women with irritable bowel syndrome (IBS). Genetic polymorphisms of monoamines are associated with fatigue in many chronic diseases. In this pilot exploratory study, the primary aim was to determine whether genetic polymorphisms of tryptophan hydroxylase ( TPH1/TPH2), serotonin reuptake transporter ( SERT), or catechol-O-methyltransferase ( COMT) are associated with fatigue in women with IBS. Additionally, analysis explored whether these genetic associations with fatigue would be present when controlling for abdominal pain, psychological distress, feeling stressed, and sleepiness during the day. Secondary analysis of two randomized controlled trial baseline data sets in Caucasian women with IBS ( N = 185) was conducted. Participants kept a daily diary with one dimension (i.e., severity) for each of the 26 symptoms, including fatigue, for 28 days prior to randomization. DNA samples were tested for single-nucleotide polymorphisms (SNPs) of TPH1 (four SNPs) /TPH2 (one SNP), SERT (one SNP), and COMT (one SNP). Analysis of covariance was used to examine associations of percentage of diary days with moderate to very severe symptoms with genetic polymorphisms. Only one SNP, TPH2 rs4570625, was significantly associated with fatigue ( p = .005). T-allele (low functional) carriers of TPH2 (i.e., G/T or T/T genotypes) reported a greater percentage of days with moderate to very severe fatigue than G/G homozygotes ( p = .001). Reduced synthesis of tryptophan in the central nervous system may contribute to reports of fatigue in women with IBS. Understanding genetic risk factors for fatigue may elucidate preemptive strategies to reduce fatigue in individuals with IBS.
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PMID:Association of Fatigue With TPH2 Genetic Polymorphisms in Women With Irritable Bowel Syndrome. 3030 44