R-5280, A Novel Modified Superior Resistant Starch Therapy for Type 1 Diabetes
R-5280,一种针对 1 型糖尿病的新型改良优质抗性淀粉疗法
基本信息
- 批准号:10759268
- 负责人:
- 金额:$ 100万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:16 year oldAcetylationAdolescentAffectAgeAmericanAmyloseAttentionAutoimmune DiseasesBeta CellBiological MarkersBiological ProductsBiological Response Modifier TherapyBlindedBody mass indexChronicCirculationClinicalClinical ResearchConsumptionContinuous Glucose MonitorDiabetes MellitusDiagnosisDietary FiberDiseaseDouble-Blind MethodDrug usageEnrollmentEnvironmentEsterificationFecesFermentationGeneticGoalsHealthHumanHuman ResourcesImmuneImmune responseImmunityImmunologicsImmunophenotypingIncidenceIndianaInflammatoryInjectableInsulinInsulin-Dependent Diabetes MellitusIntestinesLabelLeaky GutLifeLong-Term EffectsMediatingMedicalOralOral AdministrationPatientsPersonsPharmaceutical PreparationsPharmacodynamicsPharmacy facilityPhase I Clinical TrialsPhase II Clinical TrialsPlacebo ControlPlacebosPrevalenceProbioticsProcessProductionPropertyProtocols documentationQuality of lifeRandomizedResidual stateResistanceRiskSafetySeveritiesSocial InteractionSourceSpecific qualifier valueSpecimenStarchStructure of beta Cell of isletT-LymphocyteTestingTherapeuticTimeTrainingUniversitiesVolatile Fatty AcidsWell in selfautoreactive T cellbiomarker discoveryclinical trial enrollmentcommercializationcostcurative treatmentsdiabetes managementdietaryearly onsetfecal microbiomeglycemic controlgut microbiomegut microbiotaimmunomodulatory therapiesimprovedinsulin dependent diabetes mellitus onsetinsulin secretioninsulin sensitivityisletmanufacturemetabolomemetabolomicsmicrobiomenovelnovel strategiesparticipant enrollmentpatient populationphase 1 studyphase I trialphase II trialrandomized placebo controlled trialresponse biomarkersexside effectstemsuccesstreatment duration
项目摘要
Project Summary
Type 1 diabetes (T1D) is a devastating disease and there is no current curative treatment, with insulin being
the only product available. T1D affects not only glycemic control but also many important aspects of a patient's
life, including emotional well-being, quality of life, working ability, and social interactions29. In addition, persons
with T1D present increased risk of developing other serious complications. Therefore, there is an urgent need
to develop new cutting-edge strategies for T1D management.
The steep rise in the incidence and prevalence of T1D cannot be explained solely by genetic factors
implicating the environment, and specifically the gut microbiome, as a culprit for the disease
etiopathogenesis45. The gut microbiome influences multiple host functions, including immunity, and persons
with T1D present changes in gut microbiota associated with immunological deregulation and gut leakiness6.
Clinical studies demonstrate that fecal microbiome therapy (FMT) and probiotics can halt the progression of
new onset T1D13, corroborating the importance of the gut microbiome.
A promising and safe approach for the treatment of T1D that leverages the body’s own natural microbiome-
associated immune regulatory mechanisms is the use of resistant starches. High amylose starch (HAMS) is a
well-tolerated source of dietary fiber that modulate the gut microbiome and the host immune response. HAMS
consumption shifts the gut microbiome profile towards dietary fiber fermenters, producing the beneficial short
chain fatty acids SCFAs. However, HAMS only partially ameliorates T1D in humans. A potentially better
strategy is to use HAMS that has been esterified, releasing larger amounts of SCFAs in the intestinal tract and
eventually the circulation. Rise Therapeutics is developing R-5280, a modified version of HAMS that has been
butyrylated and acetylated. In our prior Phase 1 clinical trial enrolling adolescents with recent onset of T1D,
oral administration of R-5280 increased SCFA production leading to improved overall glycemic control. In
addition, R-5280 consumption resulted in significant increases in specific beneficial metabolites, and reduction
of inflammatory T cells. Given the limited success of prior therapeutic strategies and potential long-term risks of
immunomodulatory therapies in patients with T1D, the use of a microbiome modulating therapy like R-5280
offers a simple, safe, and inexpensive alternative approach to mitigating this devastating disease.
The goal of this proposal is to perform a confirmatory double blinded placebo-controlled Phase 2 clinical trial of
adolescents with early onset of T1D. The key aims of this proposal are: 1) compounding of R-5280 and
placebo to prepare for patient distribution; 2) execute the Phase 2 clinical trial; and 3) expand biomarker
discovery and characterization. Successful commercialization of R-5280 will provide a profound medical
advancement for treating T1D.
项目摘要
1型糖尿病(T1D)是一种毁灭性的疾病,目前还没有治愈的方法,胰岛素是
唯一可用的产品。T1D不仅影响血糖控制,而且还影响患者的许多重要方面
生活,包括情感幸福、生活质量、工作能力和社会交往29。此外,还有人
T1D患者发生其他严重并发症的风险增加。因此,迫切需要
为T1D管理开发新的前沿战略。
T1D发病率和患病率的急剧上升不能仅仅用遗传因素来解释
暗示环境,特别是肠道微生物群,是这种疾病的罪魁祸首
病因学45.肠道微生物群影响多种宿主功能,包括免疫力和人
与T1D相关的肠道微生物区系的变化与免疫松弛和肠道渗漏有关。
临床研究表明,粪便微生物组疗法(FMT)和益生菌可以阻止糖尿病的进展。
新发病的T1D13,证实了肠道微生物组的重要性。
一种有希望的安全的治疗T1D的方法,它利用人体自身的自然微生物群-
相关的免疫调节机制是使用抗性淀粉。高链淀粉(火腿)是一种
耐受性良好的膳食纤维来源,调节肠道微生物群和宿主免疫反应。火腿
消费使肠道微生物群组向膳食纤维发酵罐转移,产生有益的短期营养
链脂肪酸单链脂肪酸。然而,火腿只能部分改善人类的T1D。一个潜在的更好的
策略是使用已经酯化的火腿,在肠道中释放更多的单链脂肪酸和
最终影响到血液循环。Rise治疗公司正在开发R-5280,它是火腿的改良版,已经被
丁酰化和乙酰化。在我们之前的一期临床试验中,招募了最近发生T1D的青少年,
口服R-5280可增加单链脂肪酸的产生,从而改善总体血糖控制。在……里面
此外,R-5280的摄入导致特定有益代谢物显著增加,而减少
炎性T细胞。鉴于先前治疗策略的有限成功和潜在的长期风险
T1D患者的免疫调节治疗,使用R-5280等微生物组调节疗法
提供了一种简单、安全和廉价的替代方法来减轻这种毁灭性的疾病。
这项建议的目标是进行一项验证性的双盲安慰剂对照的第二阶段临床试验
T1D发病早的青少年。这项建议的主要目的是:1)R-5280和
安慰剂为患者分布做准备;2)执行第二阶段临床试验;3)扩大生物标记物
发现和表征。R-5280的成功商业化将提供深刻的医疗
T1D的治疗进展。
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)
专利数量(0)
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Gary Fanger其他文献
Gary Fanger的其他文献
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