Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children with Functional Abdominal Pain
功能性腹痛儿童的薄荷油药代动力学/动力学和新的生物特征
基本信息
- 批准号:10001107
- 负责人:
- 金额:$ 21.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-15 至 2022-09-14
- 项目状态:已结题
- 来源:
- 关键词:AbdomenAbdominal PainAddressAdultAffectAnimalsAntiinflammatory EffectBacteriaBiologicalBiological AvailabilityBiological MarkersBotanicalsCNS processingChildChildhoodChromograninsChronicChronic DiseaseCivilizationClinicalClinical ResearchClinical TrialsCommunitiesDataDevelopmentDietary CarbohydratesDiseaseDisease ManagementDistressDoseDrug KineticsEconomic BurdenEconomicsEffectivenessEmotionalFecesFrequenciesFunctional disorderGenerationsGenotypeGenus MenthaGoalsGut MucosaHealthHealth BenefitHumanHypersensitivityImmuneImmune SeraImmunologic MarkersIn VitroIndividualInflammatory disease of the intestineInternationalIrritable Bowel SyndromeIrritantsKineticsLinkLymphocyteMeasuresMentholMethodologyMucositisMucous MembraneMuscle relaxation phaseNatural ProductsOutcomePainPatient Outcomes AssessmentsPatientsPatternPeppermint oilPermeabilityPharmacodynamicsPhased Innovation AwardsPhenotypePhysiological ProcessesPhysiologyPlayQuality of lifeQuestionnairesResearch PriorityRoleSafetySample SizeSchool-Age PopulationSerum ImmunologicSmooth MuscleSymptomsTimeUGT2B7 UDP-glucuronosyltransferaseVisceralVulnerable Populationsbasebeta-Defensinscell motilityconditioned pain modulationcytokinedesigndiariesdysbiosiseffective therapygastrointestinalgastrointestinal functiongenetic variantgut bacteriagut microbiomeimprovedinnovationinsightmicrobiome compositionmultidisciplinarynovelpain processingpain symptompre-clinicalpsychosocialpublic health relevanceresearch clinical testingresponseside effectsocialtranscriptome sequencingtreatment strategy
项目摘要
DESCRIPTION (provided by applicant): Functional abdominal pain (FAP) affects 10-15% of children and adults worldwide and is characterized by chronic, intermittent abdominal pain. Symptoms range from mild to severe and debilitating and result in reduced quality of life. Up to 66% of children go on to have similar symptoms as adults. There are few effective treatments because of poor understanding of their mechanism of action (biological signatures) and of the pathophysiology of what are phenotypically and arbitrarily defined disorders. This R21/R33 application proposes to investigate the pharmaco-dynamic/kinetics (PKD) of peppermint oil (PMO), a botanical with some evidence of efficacy in adults with irritable bowel syndrome – a condition similar to FAP. We propose to study the PKD-gastrointestinal (GI) function relationships in children with FAP to link GI responses to PMO PKD, providing bioavailability data to be used to optimize dosing for a particular biological signature response, ultimately benefiting treatment and management of this disorder. No matter the outcome, our proposed study will provide an innovative and significant opportunity to develop novel data about the pathophysiology of FAP by investigating a number of biomarkers simultaneously in the same individual using cutting edge methodology to characterize gut microbiome composition and gut function in FAP. Our Specific Aims are to: R21, Aim 1 - Determine the PKD of PMO (menthol) in children with FAP (n=30). Hypothesis - a relationship exists between intraluminal/systemic menthol exposure and GI function. Sub-Hypothesis – Systemic menthol exposure after PMO reflects a genotype-phenotype relationship in subjects with allelic variants of CYP2A6 and/or UGT2B7. Aim 2 – Determine effect of PMO administration on gut microbiome composition (16S RNA sequencing) and contractile activity/gut transit rate (using the SmartPill®). Hypothesis – PMO will increase gut diversity and decrease contractile activity and gut transit. R33, Aim 1 - Confirm the findings of the R21 in a larger sample size and adjust dosing if necessary to optimize tolerability/safety and beneficial effects on gut microbiome composition and motility. Hypothesis: The findings of the R21 will be confirmed in the larger sample size. Treatment will be given for 1 week. Aim 2 – Assess the effect of PMO on pain processing (conditioned pain modulation), gut inflammation (stool beta defensin and chromogranin concentrations), and barrier function (permeability). Hypothesis: PMO will reduce visceral hypersensitivity, gut inflammation, and/or improve gut barrier function. Aim 3 - Evaluate the effect of PMO on clinical symptoms, psychosocial distress/patient reported outcomes, and acceptability (abdominal pain and stooling pattern via validated diary, pediatric PROMIS measures, side effects questionnaire). Hypothesis: PMO treatment will reduce abdominal pain frequency and patient reported outcomes will reflect this improvement.
描述(由适用提供):功能性腹痛(FAP)影响全球10-15%的儿童和成人,其特征是慢性间歇性腹痛。症状范围从轻度到重度和令人衰弱,导致生活质量降低。多达66%的儿童继续出现与成年人相似的症状。几乎没有有效的治疗方法,因为对它们的作用机理(生物)特征)以及对表型和任意定义疾病的病理生理学的了解不足。这项R21/R33申请提案要研究薄荷油(PMO)的药物动力学/动力学(PKD),这是一种植物学的证据,在肠易激综合症的成年人中有效性证据 - 类似于FAP的疾病。我们建议研究FAP儿童中的PKD-Gastrointestinal(GI)功能关系,以将GI反应与PMO PKD联系起来,从而提供生物利用度数据,以用于优化特定生物学签名反应的剂量,最终使该疾病的治疗和管理受益。无论结果如何,我们提出的研究都将提供一个创新的,重要的机会,可以通过使用尖端方法在同一个人中轻松研究许多生物标志物来开发有关FAP的病理生理学的新数据,从而表征FAP中的肠道微生物组组成和肠道功能。我们的具体目的是:R21,AIM 1-确定FAP儿童(n = 30)的PMO(薄荷醇)的PKD。假设 - 内部/全身薄荷醇的暴露与胃肠道功能之间存在关系。亚物种 - PMO后的全身薄荷醇暴露反映了CYP2A6和/或UGT2B7等位基因变体受试者中的基因型 - 表型关系。 AIM 2-确定PMO给药对肠道微生物组组成(16S RNA测序)和收缩活性/肠道运输速率(使用SmartPill®)的影响。假设 - PMO将增加肠道多样性并减少收缩活性和肠道过境。 R33,AIM 1-在较大样本量中确认R21的发现,并在必要时调整剂量,以优化对肠道微生物组组成和运动性的耐受性/安全性和有益影响。假设:R21的发现将在较大的样本量中得到确认。治疗将进行1周。 AIM 2 - 评估PMO对疼痛加工(条件疼痛调节),肠道注射(粪便β防御素和染色体蛋白浓度)和屏障功能(渗透率)的影响。假设:PMO将减少内脏的超敏反应,肠道注射和/或改善肠道屏障功能。 AIM 3-评估PMO对临床症状,社会心理困扰/患者报告的结果的影响以及可接受性(通过经过验证的日记,小儿促进症测量,副作用问卷调查表,腹痛和僵持模式)。假设:PMO治疗将降低腹部疼痛频率,患者报告的结果将反映出这一改善。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Robert J Shulman其他文献
Avoidant/restrictive food intake disorder prevalence is high in children with gastroparesis and functional dyspepsia
胃轻瘫和功能性消化不良儿童的回避/限制性食物摄入障碍患病率较高
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:3.5
- 作者:
Isha Kaul;Helen Burton;Salma Musaad;Yiming Mirabile;D. Czyzewski;Miranda A L van Tilburg;Andrew C Sher;B. Chumpitazi;Robert J Shulman - 通讯作者:
Robert J Shulman
Robert J Shulman的其他文献
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{{ truncateString('Robert J Shulman', 18)}}的其他基金
Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children with Functional Abdominal Pain
功能性腹痛儿童的薄荷油药代动力学/动力学和新的生物特征
- 批准号:
10242085 - 财政年份:2019
- 资助金额:
$ 21.56万 - 项目类别:
Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children with Functional Abdominal Pain
功能性腹痛儿童的薄荷油药代动力学/动力学和新的生物特征
- 批准号:
10015202 - 财政年份:2019
- 资助金额:
$ 21.56万 - 项目类别:
Advancing Clinical Science in Pediatric Gastroparesis
推进小儿胃轻瘫的临床科学
- 批准号:
9564280 - 财政年份:2016
- 资助金额:
$ 21.56万 - 项目类别:
Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children with Functional Abdominal Pain
功能性腹痛儿童的薄荷油药代动力学/动力学和新的生物特征
- 批准号:
9346618 - 财政年份:2016
- 资助金额:
$ 21.56万 - 项目类别:
Advancing Clinical Science in Pediatric Gastroparesis
推进小儿胃轻瘫的临床科学
- 批准号:
9554886 - 财政年份:2016
- 资助金额:
$ 21.56万 - 项目类别:
Advancing Clinical Science in Pediatric Gastroparesis
推进小儿胃轻瘫的临床科学
- 批准号:
10001460 - 财政年份:2016
- 资助金额:
$ 21.56万 - 项目类别:
Peppermint Oil Pharmacokinetics/Dynamics and Novel Biological Signatures in Children with Functional Abdominal Pain
功能性腹痛儿童的薄荷油药代动力学/动力学和新的生物特征
- 批准号:
9096507 - 财政年份:2016
- 资助金额:
$ 21.56万 - 项目类别:
Genetic Analysis of Carbohydrate Maldigestion in Irritable Bowel Syndrome
肠易激综合征碳水化合物消化不良的遗传分析
- 批准号:
8901156 - 财政年份:2014
- 资助金额:
$ 21.56万 - 项目类别:
Genetic Analysis of Carbohydrate Maldigestion in Irritable Bowel Syndrome
肠易激综合征碳水化合物消化不良的遗传分析
- 批准号:
8701693 - 财政年份:2014
- 资助金额:
$ 21.56万 - 项目类别:
Pathways to New Biomarkers in Recurrent Abdominal Pain in Children
儿童复发性腹痛新生物标志物的途径
- 批准号:
8440046 - 财政年份:2012
- 资助金额:
$ 21.56万 - 项目类别:
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