Adjuvant Nitrate to Boost Exercise-induced Health Benefits in Older Adults
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 226
- 试验地点
- 1
- 主要终点
- Assess the clinical impact of nitrate supplementation on a proportion of older adults attaining exercise-induced health benefits.
研究概览
简要总结
Aging-related functional declines are thought to be caused by hallmark biological processes that ultimately manifest in physical, mental, and metabolic impairments to compromise intrinsic capacity and healthspan. Exercise is the only multipotent treatment with promise to mitigate many of the aging hallmarks, but there is substantial variability in individual exercise responsiveness. Thus, the investigators approach to boosting exercise responsiveness in aging is to combine an exercise training prescription containing both endurance and resistance training (in alignment with DHHS guidelines) with a nitrate-enriched dietary supplement to augment the cellular, tissue, and systemic adaptations that induce myriad health benefits of exercise in older adults.
详细描述
Aging-related declines in health and intrinsic capacity are linked to biological processes profoundly affecting all organ systems and tissues including skeletal muscle. Exercise is a multipotent countermeasure to these processes. However, there is significant inter-individual response heterogeneity (IRH) in the magnitude of exercise-induced health benefits. Boosting exercise responsiveness among older adults is thus a top priority. The investigators have found in older adults that supplementation with nitric oxide (NO) precursors nitrate and nitrite is safe, well tolerated, and improves: (i) physical performance; (ii) vascular endothelial function; (iii) mitochondrial function; (iv) oxidative stress; and (v) muscle inflammation. The investigators suspect deficits among some older adults in nitrate bioavailability and/or exercise-induced NO production may in part drive suboptimal exercise responsiveness. Given the powerful and sustaining impact of exercise-induced health benefits on morbidity and mortality, the investigator's fundamental premise is that exercise responsiveness of every older adult should be maximized. In the BOOST-X Trial the investigators will determine if increasing nitrate bioavailability via dietary supplementation is an efficacious approach to more older adults attaining these essential health benefits. Low cardiorespiratory fitness (CRF, VO2max) and low functional muscle quality (fMQ; strength/muscle mass) are multi-system manifestations of degenerative aging that include vascular endothelial and mitochondrial dysfunction, oxidative stress, and inflammation. CRF and fMQ are modifiable with endurance (ET) and resistance (RT) training. This planned trial will be the first to evaluate the efficacy of coupling a nitrate-rich nutritional supplement with a combined ET+RT prescription in line with DHHS weekly exercise guidelines. The investigators will test the central hypothesis that daily nitrate supplementation will augment exercise training-induced gains in CRF and fMQ accompanied by improvements in vascular endothelial and mitochondrial function. Aim 1: Assess the clinical impact of nitrate supplementation on the proportion of older adults attaining exercise-induced health benefits. N=226 participants stratified by sex and age group (60-69 vs ≥70 y) with random assignment to nitrate (400 mg, 2x/day) (n=113) vs. placebo (nitratedepleted) (n=113) during 12 wk of 3x/wk ET+RT. 1˚ Outcomes: MCID attainment for CRF and fMQ. Expected Results: Daily nitrate will reduce the proportion of older adults not attaining CRF and fMQ MCIDs by a full 1/3. Aim 2: Assess potential mechanisms underpinning adaptations to exercise +/- nitrate supplementation. The investigators will test/integrate in vivo, ex vivo, in vitro and molecular mapping assays considered central to exercise +/- nitrate adaptations and leverage a multidimensional learning framework to better understand the biocircuitry underpinning MCID attainment. 1˚ Outcomes: Vascular endothelial function, muscle mitochondrial function. Expected Results: MCID attainment will be closely linked to improvements in vascular endothelial function and muscle mitochondrial function. The acute molecular responses to exercise will be differentially regulated by nitrate supplementation, and the novel biocircuitry will reveal key features that influence adaptability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Participants will be randomized in double-blind fashion to consume 2x/day nitrate-rich beetroot juice (Beet-it®, 400 mg inorganic nitrate per dose x 2/day) or nitrate-depleted placebo beetroot juice. To bolster trial rigor, the placebo is also produced by Beet-it®, is taste- and volume-matched, contains all other potentially bioactive ingredients sans nitrate, and active vs. placebo bottles are indistinguishable. The blind will be held by independent research staff not involved in the study. Daily consumption of each dose will be closely monitored via a phone-based logging app integrated with the electronic DEMS. The app also enables research staff to push reminders to participants as needed. Participant tolerance has not been a concern in our prior and ongoing studies. However, the investigators will monitor individual tolerance and address any issues on a case-by-case basis.
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female aged 60 years or older
- •Free of chronic disease or disorder that would preclude full participation or have the potential to confound results
- •No structured exercise program (2 or more bouts/wk) within previous 12 months
- •Cognitively capable of providing informed consent
排除标准
- •BMI ≥ 30.0 kg/m2
- •Neurodegenerative disease
- •Neuromuscular, musculoskeletal or orthopedic disorder or condition that would limit ability to perform the exercise prescription and/or physical performance testing
- •Diagnosed orthostatic hypotension, i.e., a drop in systolic blood pressure of at least 20 mmHg or a drop in diastolic blood pressure of at least 10 mmHg within three minutes of standing up from a sitting or lying position.
- •Resting blood pressure <90/60 mmHg or >160/95 mmHg
- •Uncontrolled hypertension
- •Any current cardiovascular disease or cardiopulmonary instability
- •Recent cardiovascular event or procedure within the preceding 6 months
- •If valve replacement has been performed, patient may not be enrolled for 12 months after the procedure
- •Any mechanical valve replacement that requires continuous warfarin anti-coagulation
- •Anemia: Hgb <11.0 (♂),10.0 (♂) gm/dl
- •Diabetes with HgbA1c >7.0% or fasting blood glucose ≥ 130 mg/dl
- •Liver disease with ALT > 52 U/l)
- •Chronic kidney disease (eGFR < 45)
- •Any current infectious disease
- •Any other disease or disorder that could influence exercise response, preclude full participation or have the potential to confound results (e.g., chronic lung disease, cognitive impairment, current cancer diagnosis or within 2 yr remission, cerebrovascular disease, pain)
- •Life expectancy < 1 year Medications / lifestyle
- •Insulin sensitizing/blood glucose lowering agents such as metformin
- •Currently on or have used GLP-1 agonist or other metabolic / weight loss drug in previous 12 weeks
- •Use of nitrate medications
- •High dose statin (≥40 mg/d simvastatin equivalence)
- •Chronic corticosteroids
- •Testosterone or other anabolic/androgenic hormone therapy
- •Lidocaine allergy
- •Regular tobacco use and/or vaping > 1/wk
- •Use of cannabis > 1/wk
- •Excessive alcohol consumption (3 drinks/d or 7 drinks/wk for females; 4 drinks/d or 14 drinks/wk for males)
- •Use of illicit drugs (e.g., cocaine, opioids)
- •Unable to commit to ~4 months required to complete the study
研究组 & 干预措施
Nitrate Group
Participants will be randomized to an intervention in which they take 800 mg (2 x 400 mg) nitrate-enriched beetroot juice drink [Beet It Sport Nitrate 400 (70 ml per drink)]. Both nitrate and placebo will be purchased from Beet It.
干预措施: Nitrate enriched beetroot juice (Dietary Supplement)
Placebo Group
Participants will be randomized to an intervention in which they take 800 mg (2 x 400 mg) nitrate-deprived, manufacturer-matched beetroot juice drink [Beet It Sport Nitrate 400 (70 ml per drink)]. Both nitrate and placebo will be purchased from Beet It.
干预措施: 12 week of combined exercise training (Other)
Placebo Group
Participants will be randomized to an intervention in which they take 800 mg (2 x 400 mg) nitrate-deprived, manufacturer-matched beetroot juice drink [Beet It Sport Nitrate 400 (70 ml per drink)]. Both nitrate and placebo will be purchased from Beet It.
干预措施: Nitrate depleted beetroot juice (Dietary Supplement)
Nitrate Group
Participants will be randomized to an intervention in which they take 800 mg (2 x 400 mg) nitrate-enriched beetroot juice drink [Beet It Sport Nitrate 400 (70 ml per drink)]. Both nitrate and placebo will be purchased from Beet It.
干预措施: 12 week of combined exercise training (Other)
结局指标
主要结局
Assess the clinical impact of nitrate supplementation on a proportion of older adults attaining exercise-induced health benefits.
时间窗: 12 weeks
The primary outcome will be assessed using logistic regression with the proportion not attaining Cardiorespiratory Fitness and functional Muscle Quality Minimally Clinical Differences as the response variable and treatment adjusted for sex and age group across the 12 week intervention.
次要结局
- Cardiorespiratory demand during submaximal cycle exercise.(12 weeks)
- Neuromuscular fatiguability during isometric holds.(12 weeks)
- 10 meter max gait speed.(12 weeks)
- modified Balance Error Scoring System (mBESS)(12 weeks)
- NIH PROMIS Physical Function SF(12 weeks)
- NIH PROMIS Fatigue SF(12 weeks)