Phase II Study of Nicotinamide (vitamin B3-amide) in Early-Onset Preeclampsia
烟酰胺(维生素 B3-酰胺)治疗早发性先兆子痫的 II 期研究
基本信息
- 批准号:9362186
- 负责人:
- 金额:$ 7.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-01 至 2019-08-31
- 项目状态:已结题
- 来源:
- 关键词:ADP-ribosyl CyclaseAbnormal placentationAbruptio PlacentaeAdmission activityAdverse eventAffectAgeAmidesAnimalsAntihypertensive AgentsBiological AssayBlood Coagulation DisordersBlood PlateletsBlood PressureCessation of lifeClinical ResearchClinical TrialsDataDevelopmentDietary SupplementationDiseaseDoseEarly treatmentEclampsiaEndothelin-1EnvironmentEnzymesEquilibriumFDA approvedFeasibility StudiesFetal safetyFetusFoundationsFutureGenderGoalsHemolysisHepatotoxicityHypertensionIncidenceInfantKidney FailureKnock-outLiverLiver FailureMaternal MortalityMeasuresMedicalMental disordersModelingMothersNiacinamideOralOrganPathway interactionsPhasePhase II Clinical TrialsPlacental Growth FactorPre-EclampsiaPregnancyPregnant WomenPremature BirthProtein Tyrosine KinaseProteinuriaPulmonary EdemaReportingResolutionRiskSafetySeizuresSupplementationSymptomsTestingTherapeuticTimeTranslational ResearchUmbilical Cord BloodUp-RegulationVascular EndotheliumVasospasmWaterWater-Soluble VitaminWeightWomanbaseblood pressure reductioncostdietary supplementsearly onsetendothelial dysfunctionfetalin uteroinfant morbidityinfant outcomeinnovationinsightliver functionmaternal hypertensionmaternal morbiditymaternal serummortalitymouse modelnervous system disorderoverexpressionphase 1 studyphase 2 studypre-clinicalprenatalpressurepreventpublic health relevancerandomized trialskin disordertrophoblast
项目摘要
ABSTRACT
Preeclampsia affects 5-8% of all pregnant women and accounts for almost 15% of maternal mortality. Roughly
0.5% of preeclampsia is early onset and occurs at < 34 weeks gestation, thus annually affecting up to 20,000
U.S. women and infants. There is no treatment other than delivery. Expectant management of early onset
preeclampsia (EOP) to gain in-utero time for the fetus has been reported; however half of the cases of preterm
birth in women with EOP occur due to maternal complications such as development of severe hypertension or
other end organ damage. It is believed that preeclampsia originates with shallow trophoblast invasion. This
results in activation of the vascular endothelium with subsequent upregulation of soluble fms-tyrosine kinase
(sFlt-1); stimulation of endothelin (ET)-1; and activation of ADPR-cyclase leading to potent vasocontriction.
Nicotinamide is a water-soluble vitamin that inhibits ADPR-cyclase and thus acts to reduce the downstream
effects of sFlt-1 upregulation. Using mouse models of preeclampsia characterized by ET-1 upregulation or
abnormal placentation we show that nicotinamide reduces hypertension and proteinuria and increases
maternal and fetal survival. Our phase I study of low-dose oral nicotinamide in 10 women with EOP
demonstrates safety and tolerability. Building on our preclinical and phase I study findings, the objectives of
this proposal are to test the effect of higher dose nicotinamide supplementation in women with EOP on
maternal mean arterial pressure (MAP) and further evaluate its safety. Demonstration of beneficial effects of
nicotinamide dietary supplementation on maternal BP will be the first evidence to date to support medical
treatment of EOP to attempt to delay delivery. Successful completion of this proposal will guide the
development of a future clinical study of this low cost, nontoxic dietary supplement for prolonging gestation in
EOP.
!
摘要
先兆子痫影响所有孕妇的5-8%,占孕产妇死亡率的近15%。大致
0.5%的先兆子痫是早发性的,发生在妊娠< 34周,因此每年影响多达20,000人。
美国妇女和婴儿。除了分娩,没有其他治疗方法。早发型期待治疗
已经报道了先兆子痫(EOP)以获得胎儿在子宫内的时间;然而,
患有EOP的妇女分娩是由于母体并发症,如严重高血压的发展,
其他器官损伤。据信,先兆子痫起源于浅滋养细胞侵入。这
导致血管内皮的活化以及随后可溶性FMS-酪氨酸激酶的上调
(sFlt-1);内皮素(ET)-1的刺激;和ADPR-环化酶的激活,导致有效的血管收缩。
烟酰胺是一种水溶性维生素,其抑制ADPR-环化酶,从而起到减少下游代谢的作用。
sFlt-1上调的影响。使用以ET-1上调或
我们发现,烟酰胺可降低高血压和蛋白尿,
母亲和胎儿的存活率。我们在10名EOP女性中进行的低剂量口服烟酰胺的I期研究
证明了安全性和耐受性。基于我们的临床前和I期研究结果,
该建议旨在测试EOP女性患者补充更高剂量的烟酰胺对
母体平均动脉压(MAP),并进一步评价其安全性。证明的有益效果
烟酰胺膳食补充剂对母体血压的影响将是迄今为止支持医疗保健的第一个证据。
治疗EOP以延迟分娩。成功完成这一提案将指导
开发这种低成本,无毒的膳食补充剂用于延长妊娠的未来临床研究,
EOP。
!
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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Kim A Boggess其他文献
Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Pregnancy-Reply.
二甲双胍加胰岛素治疗已有糖尿病或妊娠期糖尿病 - 回复。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Kim A Boggess - 通讯作者:
Kim A Boggess
Kim A Boggess的其他文献
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{{ truncateString('Kim A Boggess', 18)}}的其他基金
Structural racism and cardiovascular disease risk in pregnant women and their infants
孕妇及其婴儿的结构性种族主义和心血管疾病风险
- 批准号:
10674302 - 财政年份:2022
- 资助金额:
$ 7.6万 - 项目类别:
Arterial stiffness in mother/infant dyads: Life course approach to prevent cardiovascular disease
母婴二人的动脉僵硬度:预防心血管疾病的生命全程方法
- 批准号:
10581158 - 财政年份:2021
- 资助金额:
$ 7.6万 - 项目类别:
Arterial stiffness in mother/infant dyads: Life course approach to prevent cardiovascular disease
母婴二人的动脉僵化:预防心血管疾病的生命全程方法
- 批准号:
10418688 - 财政年份:2021
- 资助金额:
$ 7.6万 - 项目类别:
Arterial stiffness in mother/infant dyads: Life course approach to prevent cardiovascular disease
母婴二人的动脉僵化:预防心血管疾病的生命全程方法
- 批准号:
10667504 - 财政年份:2021
- 资助金额:
$ 7.6万 - 项目类别:
Arterial stiffness in mother/infant dyads: Life course approach to prevent cardiovascular disease
母婴二人的动脉僵化:预防心血管疾病的生命全程方法
- 批准号:
10912921 - 财政年份:2021
- 资助金额:
$ 7.6万 - 项目类别:
Arterial stiffness in mother/infant dyads: Life course approach to prevent cardiovascular disease
母婴二人的动脉僵化:预防心血管疾病的生命全程方法
- 批准号:
10912923 - 财政年份:2021
- 资助金额:
$ 7.6万 - 项目类别:
Arterial stiffness in mother/infant dyads: Life course approach to prevent cardiovascular disease
母婴二人的动脉僵化:预防心血管疾病的生命全程方法
- 批准号:
10182318 - 财政年份:2021
- 资助金额:
$ 7.6万 - 项目类别:
VALIDATION OF SELF-REPORT TOOL TO SCREEN FOR PERIODONTAL DISEASE AMONG PREGNANT
孕妇牙周疾病筛查自我报告工具的验证
- 批准号:
7716915 - 财政年份:2008
- 资助金额:
$ 7.6万 - 项目类别:
Understanding Barriers to Oral Health Care In Pregnancy: The First Step to Improv
了解妊娠期口腔保健的障碍:改善的第一步
- 批准号:
7342364 - 财政年份:2007
- 资助金额:
$ 7.6万 - 项目类别:
Understanding Barriers to Oral Health Care In Pregnancy: The First Step to Improv
了解妊娠期口腔保健的障碍:改善的第一步
- 批准号:
7487003 - 财政年份:2007
- 资助金额:
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