The Inorganic Nitrate and eXercise performance in Heart Failure (iNIX-HF): - a phase II clinical trial

无机硝酸盐和运动在心力衰竭中的表现 (iNIX-HF):- II 期临床试验

基本信息

  • 批准号:
    10449833
  • 负责人:
  • 金额:
    $ 80.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-08-01 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Heart failure with reduced ejection fraction (HFrEF) affects ~3 million people in the U.S. and is a mortal and morbid disease. HFrEF impairs a patient’s ability to exercise and perform activities of daily living. Although weak cardiac pumping ability clearly contributes to chronic disability associated with HFrEF, abnormal skeletal muscle function in patients with HFrEF is also a key debilitating factor. Skeletal muscle is therefore a vital target for treatment of HFrEF. Dietary inorganic nitrate enhances aerobic exercise capacity and muscle power in patients with HFrEF, as demonstrated in our preliminary studies. The overarching aim of the proposed clinical trial is to determine whether inorganic nitrate in a once-a-day oral gelcap format, offers a new, safe, and effective treatment for ameliorating the impaired exercise performance due to HFrEF. The Aim of the R61 component of this grant is to set up the infrastructure necessary for the phase II clinical trial and to begin the trial. This includes compounding the inorganic nitrate (KNO3)/placebo capsules and all safety testing, obtaining Institutional Review Board approval, ClinicalTrials.gov registration, REDCap database development, Recruitment Enhancement Core (REC) engagement, Clinical Translational Research Unit (CTRU) project approval, enrollment and assessment and dose administration of the first subjects. The Aims of the R33 component are to determine the effectiveness of acute (2 hours after a single dose) and chronic (after 6 weeks of once-a-day dosing) KNO3 treatment (10mmol) vs. placebo on quadriceps muscle power and on aerobic exercise performance (V̇O2peak) in patients with HFrEF (left ventricular ejection fraction <45%). We hypothesize that both acute and chronic dosing of 10mmol of KNO3 will improve exercise performance in HFrEF. To test this hypothesis, we will perform a randomized, double-blind, placebo-controlled, parallel-arm design study. Patients with stable New York Heart Association class I-III HFrEF will undergo screening and phenotyping before completing baseline peak muscle power and aerobic performance measurements. On visit 2, subjects will receive a single dose (1 capsule) of their assigned treatment (10mmol KNO3 or placebo) and will repeat the measurements of exercise performance after 2h. Subjects will then continue with their assigned treatment (KNO3 or placebo, 1 capsule daily) for 6 weeks. On visit 3, subjects will repeat the tests of exercise performance. The primary endpoints are maximum quadriceps muscle power, measured using an isokinetic dynamometer, and aerobic exercise performance, based on V̇O2peak. Max exercise time and max muscle velocity, tolerability and safety of KNO3 vs. placebo treatment and their effects on hemodynamics, plasma nitrate, plasma nitrite, breath nitric oxide (NO), and heart failure symptoms (using well-validated questionnaires) will also be quantified in this phase II, single-center clinical trial. The potential impact of finding a new, safe and effective treatment that helps millions of patients beat the physical disability of HFrEF is enormous.
摘要 射血分数降低的心力衰竭(HFrEF)影响美国约300万人,并且是致命的, 病态的疾病HFrEF损害患者锻炼和进行日常生活活动的能力。虽弱 心脏泵血能力明显导致与HFrEF、异常骨骼肌相关的慢性残疾 HFrEF患者的功能也是一个关键的衰弱因素。因此,骨骼肌是一个重要的目标, 治疗HFrEF。膳食无机硝酸盐增强患者有氧运动能力和肌肉力量 正如我们的初步研究所证明的那样。拟议临床试验的总体目标是 确定是否无机硝酸盐在一天一次的口服胶囊形式,提供了一个新的,安全的,有效的 用于改善由于HFrEF而导致的受损的运动表现的治疗。 这笔赠款的R61部分的目的是建立第二阶段所需的基础设施。 临床试验并开始开始试验。这包括复合无机硝酸盐(KNO 3)/安慰剂胶囊, 所有安全性测试,获得机构审查委员会批准,ClinicalTrials.gov注册,REDCap 数据库开发、招聘增强核心(REC)参与、临床转化研究 单位(CTRU)项目批准、入组和评估以及首批受试者的给药。 R33组分的目的是确定急性(单次给药后2小时) 和慢性(每天一次给药6周后)KNO 3治疗(10 mmol)与安慰剂对四头肌的影响 HFrEF(左心室射血分数)患者的功率和有氧运动能力(V ~ O2峰值) <45%)。我们假设,无论是急性和慢性剂量的10毫摩尔硝酸钾将改善运动 在HFrEF中的表现。为了检验这一假设,我们将进行一项随机、双盲、安慰剂对照、 平行臂设计研究。稳定的纽约心脏协会I-III级HFrEF患者将接受 在完成基线峰值肌肉力量和有氧能力之前进行筛选和表型分析 测量.访视2时,受试者将接受单次剂量(1粒胶囊)的分配治疗(10 mmol KNO 3或安慰剂),并在2小时后重复测量运动表现。受试者将继续 接受指定治疗(KNO 3或安慰剂,每日1粒胶囊)6周。访视3时,受试者将重复 运动表现测试。主要终点是最大股四头肌肌力,使用 等速测力计和有氧运动性能,基于V ~ 2O_2峰值。最大锻炼时间和最大 KNO 3与安慰剂治疗相比的肌肉速度、耐受性和安全性及其对血流动力学、血浆 硝酸盐、血浆亚硝酸盐、呼吸一氧化氮(NO)和心力衰竭症状(使用经过充分验证的问卷) 也将在该II期单中心临床试验中进行量化。寻找一种新的安全的 帮助数百万患者战胜HFrEF身体残疾的有效治疗是巨大的。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

ANDREW R COGGAN其他文献

ANDREW R COGGAN的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('ANDREW R COGGAN', 18)}}的其他基金

The Inorganic Nitrate and eXercise performance in Heart Failure (iNIX-HF): - a phase II clinical trial
无机硝酸盐和运动在心力衰竭中的表现 (iNIX-HF):- II 期临床试验
  • 批准号:
    10731565
  • 财政年份:
    2022
  • 资助金额:
    $ 80.38万
  • 项目类别:
Dietary Nitrate and Muscle Power with Aging
膳食硝酸盐与衰老过程中的肌肉力量
  • 批准号:
    9764237
  • 财政年份:
    2018
  • 资助金额:
    $ 80.38万
  • 项目类别:
THE INORGANIC NITRATE FOR EXERCISE IN HEART FAILURE (INIX-HF) TRIAL
用于心力衰竭锻炼的无机硝酸盐 (INIX-HF) 试验
  • 批准号:
    9754867
  • 财政年份:
    2017
  • 资助金额:
    $ 80.38万
  • 项目类别:
THE INORGANIC NITRATE FOR EXERCISE IN HEART FAILURE (INIX-HF) TRIAL
用于心力衰竭锻炼的无机硝酸盐 (INIX-HF) 试验
  • 批准号:
    9374210
  • 财政年份:
    2017
  • 资助金额:
    $ 80.38万
  • 项目类别:
EFFECT OF GENDER ON SUBSTRATE UTILIZATION DURING SUBMAXIMAL EXERCISE
性别对次极量运动期间基质利用的影响
  • 批准号:
    6115180
  • 财政年份:
    1998
  • 资助金额:
    $ 80.38万
  • 项目类别:
AGING AND SKELETAL MUSCLE FATTY ACID METABOLISM
衰老与骨骼肌脂肪酸代谢
  • 批准号:
    2387920
  • 财政年份:
    1997
  • 资助金额:
    $ 80.38万
  • 项目类别:
AGING AND SKELETAL MUSCLE FATTY ACID METABOLISM
衰老与骨骼肌脂肪酸代谢
  • 批准号:
    2769437
  • 财政年份:
    1997
  • 资助金额:
    $ 80.38万
  • 项目类别:
AGING AND SKELETAL MUSCLE FATTY ACID METABOLISM
衰老与骨骼肌脂肪酸代谢
  • 批准号:
    2832413
  • 财政年份:
    1997
  • 资助金额:
    $ 80.38万
  • 项目类别:
EFFECT OF GENDER ON SUBSTRATE UTILIZATION DURING SUBMAXIMAL EXERCISE
性别对次极量运动期间基质利用的影响
  • 批准号:
    6276415
  • 财政年份:
    1997
  • 资助金额:
    $ 80.38万
  • 项目类别:
FREE FATTY ACID AVAILABILITY ON PLASMA GLUCOSE KINETICS DURING EXERCISE
运动期间血浆葡萄糖动力学中游离脂肪酸的可用性
  • 批准号:
    3882878
  • 财政年份:
  • 资助金额:
    $ 80.38万
  • 项目类别:

相似海外基金

The effects of acute aerobic exercise on hippocampal function and microstructure in older adults
急性有氧运动对老年人海马功能及微结构的影响
  • 批准号:
    10548811
  • 财政年份:
    2022
  • 资助金额:
    $ 80.38万
  • 项目类别:
The effects of acute aerobic exercise on hippocampal function and microstructure in older adults
急性有氧运动对老年人海马功能及微结构的影响
  • 批准号:
    10314779
  • 财政年份:
    2022
  • 资助金额:
    $ 80.38万
  • 项目类别:
The effects of acute aerobic exercise on hippocampal function and microstructure in older adults
急性有氧运动对老年人海马功能及微结构的影响
  • 批准号:
    10580466
  • 财政年份:
    2022
  • 资助金额:
    $ 80.38万
  • 项目类别:
The Effects of Blood Flow Restriction During Acute Aerobic Exercise on Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1a) Expression
急性有氧运动期间血流限制对过氧化物酶体增殖物激活受体γ共激活物1-α(PGC-1a)表达的影响
  • 批准号:
    529237-2018
  • 财政年份:
    2018
  • 资助金额:
    $ 80.38万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
The Influence of Acute Bouts of Aerobic Exercise on Neuroplasticity and Motor Learning after Stroke
急性有氧运动对中风后神经可塑性和运动学习的影响
  • 批准号:
    343900
  • 财政年份:
    2016
  • 资助金额:
    $ 80.38万
  • 项目类别:
    Operating Grants
The potentiation of neurovascular coupling in cognitive-brain areas following acute aerobic exercise
急性有氧运动后认知脑区域神经血管耦合的增强
  • 批准号:
    460143-2014
  • 财政年份:
    2016
  • 资助金额:
    $ 80.38万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
The effects of acute aerobic exercise on memory function
急性有氧运动对记忆功能的影响
  • 批准号:
    15K12687
  • 财政年份:
    2015
  • 资助金额:
    $ 80.38万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
The potentiation of neurovascular coupling in cognitive-brain areas following acute aerobic exercise
急性有氧运动后认知脑区域神经血管耦合的增强
  • 批准号:
    460143-2014
  • 财政年份:
    2015
  • 资助金额:
    $ 80.38万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Potential for gene expression by acute aerobic exercise with locally force of muscle
局部肌肉力量急性有氧运动的基因表达潜力
  • 批准号:
    26750317
  • 财政年份:
    2014
  • 资助金额:
    $ 80.38万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
The potentiation of neurovascular coupling in cognitive-brain areas following acute aerobic exercise
急性有氧运动后认知脑区域神经血管耦合的增强
  • 批准号:
    460143-2014
  • 财政年份:
    2014
  • 资助金额:
    $ 80.38万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了