NCT04848675

Novel Time-efficient Inspiratory Muscle Strength Training for Lowering Systolic Blood Pressure

Status unknown NA Last updated 2 November 2023

What this trial tests

NA trial testing Inspiratory muscle strength training in Blood Pressure in 102 participants. Status unknown.

Timeline

7 May 2021

Primary endpoint
1 May 2025

31 May 2025

Quick facts

Lead sponsor	University of Colorado, Boulder
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	102
Start date	7 May 2021
Primary completion	1 May 2025
Estimated completion	31 May 2025
Sites	1 location across United States

Drugs / interventions tested

• Inspiratory muscle strength training
• Brisk walking

Conditions studied

• Blood Pressure — all drugs for Blood Pressure →
• Endothelial Dysfunction — all drugs for Endothelial Dysfunction →
• Hypertension — all drugs for Hypertension →

Sponsor

University of Colorado, Boulder

Who can join

50 and older, any sex, with Blood Pressure or Endothelial Dysfunction. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Above-normal systolic blood pressure (SBP), defined as SBP \>/= 120 mmHg, is the major modifiable risk factor for cardiovascular disease, stroke, cognitive decline/dementia, and other chronic health problems. Despite the availability of treatments to lower SBP, over 75 percent of adults with above-normal SBP fail to control BP, which has led to a nearly 50 percent increase in the number of deaths attributable to BP over the past decade. Therefore, above-normal SBP is a major public health burden.

* Greater than 65 percent of adults 50 years of age and older have above-normal SBP. The number of adults age 50 years and older is rapidly increasing, predicting a continued increase in above-normal SBP driven morbidity and mortality in the absence of effective treatment strategies. This makes developing novel SBP-lowering therapies an urgent biomedical research priority.
* Increasing SBP is closely linked to vascular dysfunction, observable as impaired endothelial function, increased large-elastic artery stiffness, and impaired cerebrovascular function. Declines in these functions play a large role in the increased risk of chronic disease associated with above-normal SBP. The primary mechanism responsible for SBP-induced vascular dysfunction is thought to be oxidative stress-associated inhibition of nitric oxide bioavailability. Therefore, to have the largest biomedical impact, new SBP-lowering therapies should also improve vascular function by decreasing oxidative stress.
* Healthy lifestyle practices, such as conventional aerobic exercise, maintaining a healthy diet, or reducing sodium intake, are all first-line strategies to lower SBP. Importantly, these lifestyle practices also improve vascular function, in large part by reducing oxidative stress. However, adherence to healthy lifestyle practices is poor, with adherence to guidelines generally between 20 to 40 percent in adult Americans. The greatest reported barrier to meeting healthy lifestyle guidelines is lack of time. Therefore, time-efficient interventions have great promise for promoting adherence, reducing SBP, and improving other physiological functions.
* High-resistance inspiratory muscle strength training (IMST) is a time-efficient (5 minutes per session) lifestyle intervention consisting of 30 inspiratory maneuvers performed against a high resistance. Preliminary data suggest 6-weeks of IMST performed 6 days/week reduces SBP by 9 mmHg in adults with above-normal SBP (i.e., greater than 120 mmHg) at baseline. Importantly, this reduction in SBP is equal to or greater than the reduction in blood pressure typically achieved with time- and effort-intensive healthy lifestyle strategies like conventional aerobic exercise. However, these results need to be confirmed in an appropriately powered clinical trial with a longer, guideline-based treatment duration. Furthermore, the influence of IMST on functions impaired by above-normal SBP (endothelial, cerebrovascular, cognitive) needs to be determined, as do the mechanisms through which IMST exerts beneficial effects.
* Accordingly, we will conduct a randomized, blinded, sham-controlled, parallel group design clinical trial to assess the efficacy of 3-months of IMST (75 percent maximal inspiratory pressure) vs. brisk walking (40-60% heart rate reserve; an established healthy lifestyle strategy) for lowering SBP and improving endothelial, cerebrovascular, and cognitive function in adults age 50 years and older with above-normal SBP. I hypothesize IMST will lower SBP and improve endothelial function by decreasing oxidative stress and increasing nitric oxide bioavailability. I also hypothesize IMST will improve cerebrovascular and cognitive function, and that these improvements will be related to reductions in SBP and improvements in endothelial function. I also expect adherence to the intervention to be excellent (over 80 percent of all training sessions completed at the appropriate intensity).
* To test my hypothesis, I will recruit 102 adults age 50 years and older who have SBP \>/= 120 mmHg. Subjects will undergo baseline testing for casual (resting) SBP, 24-hour ambulatory SBP, endothelial function, arterial stiffness, cognitive function, and cerebrovascular function. Innovative mechanistic probes including pharmaco-dissection with vitamin C, analysis of biopsied endothelial cells, and high-throughput metabolomics, will be performed to assess oxidative stress and nitric oxide bioavailability at baseline.
* After baseline testing, subjects will be randomized to perform either 3-months of high-resistance IMST or brisk walking. Subjects will train 6 days/week with one training session supervised in the laboratory and the other 5 performed unsupervised at home. Following 3 months of training, subjects will redo all the tests that were done during baseline testing to assess training-induced changes in SBP, physiological functions, and underlying mechanisms.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Aging, aerobic exercise, and cardiovascular health: Barriers, alternative strategies and future directions.
   Murray KO, Mahoney SA, Venkatasubramanian R, Seals DR, et al · · 2023 · cited 32× · PMID 36731386 · DOI 10.1016/j.exger.2023.112105
2. Promoting healthy cardiovascular aging: emerging topics.
   Clayton ZS, Craighead DH, Darvish S, Coppock M, et al · · 2022 · cited 19× · PMID 36337728 · DOI 10.20517/jca.2022.27
3. Time-efficient, high-resistance inspiratory muscle strength training increases cerebrovascular reactivity in midlife and older adults.
   Freeberg KA, Craighead DH, Heinbockel TC, Rossman MJ, et al · · 2023 · cited 13× · PMID 37682232 · DOI 10.1152/ajpheart.00351.2023
4. Translational Potential of High-Resistance Inspiratory Muscle Strength Training.
   Craighead DH, Freeberg KA, Maurer GS, Myers VH, et al · · 2022 · cited 10× · PMID 35394978 · DOI 10.1249/jes.0000000000000293
5. Sex Differences in Dementia and Mild Cognitive Impairment in Nondialysis CKD.
   Oh ES, Opoku G, Darvish S, Craighead DH, et al · · 2026 · PMID 41264372 · DOI 10.2215/cjn.0000000922