长期 COVID 患者的亚硝酸盐补充剂
2026年8月3日 更新者：VA Office of Research and Development
亚硝酸盐补充剂可减轻长期 COVID 患者的疲劳并增加功能
将在 Long COVID 患者中研究硝酸盐汁补充剂改善骨骼肌功能和相关身体能力的潜在益处。
同意的 Long-COVID 患者将被随机分配到 Beet-It 硝酸盐饮料组和不含硝酸盐的安慰剂饮料组。
两组都将在 VAPHS 的长期 COVID 诊所接受物理治疗，治疗目标是提高力量、平衡、吸气和有氧能力。
物理治疗将持续 2 周，包括每周与物理治疗师进行 2 或 3 次疗程，具体取决于每个人的运动耐力。
这些会议可以在现场或家中（或混合组合）进行。在为期 14 天的研究干预之前和之后，所有参与者都将接受功能评估和组织评估。
研究概览
详细说明
在概念验证试验中，研究人员将研究 40 名患有长期 COVID 的退伍军人，将 20 名每天食用富含硝酸盐的甜菜根汁两周的人与食用不含硝酸盐的安慰剂的匹配退伍军人进行比较。 硝酸盐一旦被摄入就会代谢增加细胞一氧化氮。 一氧化氮 (NO) 是一种信号分子，有助于许多生理功能，包括增强骨骼肌线粒体呼吸，从而可能导致疲劳性降低和身体机能增加。 NO 通常由氨基酸 L-精氨酸在氧气存在下转化为 L-瓜氨酸产生。 然而，作为膳食补充剂提供的无机硝酸盐可以作为生物活性亚硝酸盐和下游 NO 的额外底物，特别是在运动的缺血应激期间。 在这项研究中，同意的 Long-COVID 患者将随机接受 Beet-It 硝酸盐饮料组作为无机亚硝酸盐和 NO 的来源，与硝酸盐耗尽的安慰剂饮料相比。 两组将同时接受物理治疗。 主要终点以有意义的临床变化为中心，包括易疲劳性（即在稳态步行期间感知的用力等级）、心肺健康（即峰值氧利用率 [VO2] 以及无氧阈值下的次最大 VO2 [VAT]）。 此外，血清学和骨骼肌评估将包括硝酸盐和亚硝酸盐水平以及线粒体呼吸，以分析亚硝酸盐介导的潜在功能变化机制。
首席研究员 Daniel Forman 医学博士在使用亚硝酸盐胶囊补充剂治疗久坐不动和心力衰竭的老年人方面积累了亚硝酸盐疗法方面的专业知识。 该 SPiRE 提案将亚硝酸盐疗法的重点放在了患有长期 COVID 的年轻人和老年人身上。
目的：进行一项随机对照试验，研究甜菜根汁与安慰剂对 40 名先前感染过 COVID-19（一年内）并且留下长期 COVID 残留症状的退伍军人的益处。 所有参与者将接受为期 2 周的每日研究果汁干预，并结合物理治疗和旨在增加力量和有氧功能的标准化运动方案
- 目的 1：研究亚硝酸盐补充剂在两周内降低易疲劳性的功效，这是通过在每小时 1.5 英里的次最大稳态步行期间的感知用力 (RPE) 等级来衡量的。 还将在稳态步行期间评估步行效率（每公斤 VO2）。
- 目标 2：研究补充亚硝酸盐对提高心肺健康（峰值氧利用率 [VO2]、无氧阈值 (VAT) 下的 VO2、6 分钟步行距离 (6MWD)、短体能电池 (SPPB) 和肺功能）的益处两周后进行测试 (PFT)。
- 目标 3：通过离体 Oroboros 分析，探索补充亚硝酸盐对增强长 COVID 患者骨骼肌线粒体呼吸的效用。
研究类型
介入性
注册 (实际的)
17
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Pennsylvania
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Pittsburgh、Pennsylvania、美国、15240
- VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
描述
纳入标准：
- 先前患有 COVID-19 的退伍军人，具有长期 COVID 的残余症状，包括易疲劳性增加（即稳态行走期间 RPE 10 和体力活动减少（<8 Mets/天））。
- 纳入仅限于 18 岁及以上
排除标准：
- 血压 <110/60 mmHg，收缩压或舒张压值
- 在肌肉活检前无法停用华法林、新型口服抗凝剂 (NOAC) 或阿司匹林 3 天，或在肌肉活检前无法停用噻吩并吡啶类药物 5 天
- 当前使用有机硝酸盐或 5 型磷酸二酯酶 (PDE5) 抑制剂
- 限制身体活动或功能测试评估的骨科或其他慢性疾病
- 终末期疾病
- 痴呆或其他原因无法给予知情同意
- 贫血（血红蛋白 <11.0 g/dL 或 <10.0 g/dL）
- 不稳定的精神病学诊断
- 有临床意义的酒精摄入（CAGE 评分 2 或 >）或药物滥用
- 长期使用口服皮质类固醇或影响肌肉功能的药物
- 使用混淆硝酸盐/亚硝酸盐/NO途径的抗菌漱口水或抗酸剂。
- 参与另一项大于最小风险的研究
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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有源比较器：甜菜 - 硝酸盐饮料
参与者每天将获得14天的硝酸盐饮料每天140毫升。 将鼓励所有参与者每周接受2-3次物理疗法，以每次会议后所需的活动和恢复的耐受性进行2-3次。 物理疗法将被标准化，包括力量，平衡，灵感肌肉训练和有氧训练。 将在基线时评估随机分配到该部门的参与者，并在所有结果指标上进行随访。 |
研究人员建议使用富含硝酸盐的甜菜根果汁来增加亚硝酸盐疗法的益处，以增加血清亚硝酸盐。
研究人员假设亚硝酸盐增加将改善功能指标，并减少由于骨骼肌线粒体呼吸增强而导致的持续共同的退伍军人的疲劳性。
与安慰剂与安慰剂相比，参与者每天将获得16 mmol硝酸盐/天的硝酸盐硝酸盐饮料140毫升。
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安慰剂比较：硝酸盐耗尽的安慰剂
参与者将获得210毫升硝酸盐的安慰剂14天。 将鼓励所有参与者每周接受2-3次物理疗法，以每次会议后所需的活动和恢复的耐受性进行2-3次。 物理疗法将被标准化，包括力量，平衡，灵感肌肉训练和有氧训练。 将在基线时评估随机分配到该部门的参与者，并在所有结果指标上进行随访。 |
随机分配到安慰剂臂的参与者每天将获得210毫升硝酸盐耗尽的饮料（蔓越莓汁）14天。
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Fatigability
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
Rating of Rate of Perceived Exertion (RPE) during the 5th minute of a 5-min of a 1.5 mile per hour steady-state treadmill walking test is used as an assessment of fatigability.
RPE scale is from 6 (no physical exertion) - 20 (maximal exertion/very hard).
This is assessed before and after approx.
14 days of supplementation with Beet-It nitrate beverage vs. placebo.
The mean change from baseline to follow-up is used as the outcome measure.
|
Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
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Walking Efficiency
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
Walking efficiency (VO2/kg) is assessed by incorporating VO2 assessments during the 5-min steady-state walking protocol.
This is assessed using cardiopulmonary exercise testing (CPET) equipment.
A lower VO2 for the same functional workload indicates improved efficiency.
This is assessed before and after approx.
14 days of supplementation with Beet-It nitrate beverage vs. placebo.
The mean change from baseline to follow-up is used as the outcome measure.
|
Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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血清硝酸盐
大体时间：基线（干预前）进行随访（干预后）；大约2周
|
将从参与者那里收集5毫升的血液，并使用离心机向下旋转，以将血浆与其他血液分开。
血清学采样在基线和最终访问时完成。
血清亚硝酸盐（µmol/L）和硝酸盐水平（µmol/L）将在基线和研究干预后测量以评估硝酸盐（在甜菜根汁中）对亚硝酸盐的成功代谢。
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基线（干预前）进行随访（干预后）；大约2周
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血清亚硝酸盐
大体时间：基线（干预前）进行随访（干预后）；大约2周
|
将从参与者那里收集5毫升的血液，并使用离心机向下旋转，以将血浆与其他血液分开。
血清学采样在基线和最终访问时完成。
血清亚硝酸盐（µmol/L）和硝酸盐水平（µmol/L）将在基线和研究干预后测量以评估硝酸盐（在甜菜根汁中）对亚硝酸盐的成功代谢。
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基线（干预前）进行随访（干预后）；大约2周
|
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400m Corridor Walk Test (400MCW)
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
This test measures the amount of time it takes the participant to walk a 400-meter course to assess cardiovascular and pulmonary fitness or to predict adverse outcomes such as mobility disability.
his is assessed before and after approx.
14 days of supplementation with Beet-It nitrate beverage vs. placebo.
The mean change from baseline to follow-up is used as the outcome measure.
|
Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
|
Short Performance Physical Battery (SPPB)
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
The SPPB is a test of balance, gait, strength, and endurance that combines gait speed, chair stand and balance tests.
SPPB scaled score ranges from 0 - 12. Scores of 0 indicate that the participant is unable/barely able to perform the tasks, while 12 indicates they completed all tasks optimally.
This is assessed before and after approx.
14 days of supplementation with Beet-It nitrate beverage vs. placebo.
The mean change from baseline to follow-up is used as the outcome measure.
|
Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
|
Peak Oxygen Utilization (VO2) Non-normalized
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
Peak VO2 (ml/min) non-normalized to weight will be collected using symptom-limited cardiopulmonary exercise testing (CPET).
This is assessed before and after approx.
14 days of supplementation with Beet-It nitrate beverage vs. placebo.
The mean change from baseline to follow-up is used as the outcome measure.
|
Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
|
Peak Oxygen Utilization (VO2) Normalized to Weight
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
Peak VO2 will be collected using symptom-limited cardiopulmonary exercise testing (CPET).
The average sedentary male will achieve a peak VO2 of approximately 35 to 40 mL/kg/min.
The average sedentary female will score a VO2 max of between 27 and 30 mL/kg/min.
This is assessed before and after approx.
14 days of supplementation with Beet-It nitrate beverage vs. placebo.
The mean change from baseline to follow-up is used as the outcome measure.
|
Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
|
VO2 at Anaerobic Threshold (AT) Non-normalized
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
VO2 (ml/min) non-normalized at AT will be assessed using symptom-limited CPET.
The VO2 at AT for the general population occurs at approximately 50-60% of the peak VO2.
This is assessed before and after approx.
14 days of supplementation with Beet-It nitrate beverage vs. placebo.
The mean change from baseline to follow-up is used as the outcome measure.
|
Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
|
VO2 at Anaerobic Threshold (AT) Normalized to Weight
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
VO2 (ml/kg/min) at AT will be assessed using symptom-limited CPET.
The VO2 at AT for the general population occurs at approximately 50-60% of the peak VO2.
This is assessed before and after approx.
14 days of supplementation with Beet-It nitrate beverage vs. placebo.
The mean change from baseline to follow-up is used as the outcome measure.
|
Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
|
Mitochondrial Respiration
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
To determine the impact of nitrite-rich juice supplementation on skeletal muscle mitochondrial respiration on patients with Long COVID, muscle biopsy of the vastus lateralis will be completed at baseline and following 2 weeks of supplementation.
At each time point muscle respiratory capacity will be measured using the Oroboros-2k system.
The main outcome will be change in state 3 respiration (maxOXPHOS, pmol/mg/min wet.wt.).
Data will be reported as Mean +/- standard deviation.
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Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
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Veterans RAND-12 (VR-12)
大体时间：Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
|
The Veterans RAND-12 (VR-12) is a brief self-administered health survey comprised of 12 items used to measure health related quality of life, estimate disease burden, and evaluate disease-specific benchmarks using two score components: Physical Component Score (PCS) and Mental Component Score (MCS).
Summary scores are standardized using a t-score transformation (normalized to US population with mean of 50 and standard deviation of 10).
A higher PCS represents better self-reported overall physical function; a higher MCS represents better emotional well-being and fewer mental health limitations.
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Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Daniel E Forman, MD、VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
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- Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, Privette G, Yim E, Kraus WE, Allen JD. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol (1985). 2011 Jun;110(6):1582-91. doi: 10.1152/japplphysiol.00071.2011. Epub 2011 Mar 31.
- Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007 Sep;191(1):59-66. doi: 10.1111/j.1748-1716.2007.01713.x. Epub 2007 Jul 17.
- Balady GJ, Arena R, Sietsema K, Myers J, Coke L, Fletcher GF, Forman D, Franklin B, Guazzi M, Gulati M, Keteyian SJ, Lavie CJ, Macko R, Mancini D, Milani RV; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Peripheral Vascular Disease; Interdisciplinary Council on Quality of Care and Outcomes Research. Clinician's Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation. 2010 Jul 13;122(2):191-225. doi: 10.1161/CIR.0b013e3181e52e69. Epub 2010 Jun 28. No abstract available.
- Eggebeen J, Kim-Shapiro DB, Haykowsky M, Morgan TM, Basu S, Brubaker P, Rejeski J, Kitzman DW. One Week of Daily Dosing With Beetroot Juice Improves Submaximal Endurance and Blood Pressure in Older Patients With Heart Failure and Preserved Ejection Fraction. JACC Heart Fail. 2016 Jun;4(6):428-37. doi: 10.1016/j.jchf.2015.12.013. Epub 2016 Feb 10.
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研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2023年12月1日
初级完成 (实际的)
2025年2月12日
研究完成 (实际的)
2025年2月14日
研究注册日期
首次提交
2022年11月14日
首先提交符合 QC 标准的
2022年11月14日
首次发布 (实际的)
2022年11月16日
研究记录更新
最后更新发布 (实际的)
2026年8月26日
上次提交的符合 QC 标准的更新
2026年8月3日
最后验证
2026年8月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- F4409-P
- 1I21RX004409 (美国 NIH 拨款/合同)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
不
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
在美国制造并从美国出口的产品
不
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