Inspiratory Muscle Strength Training in Chronic Kidney Disease

NCT04911491 | Recruiting DMC FDA Device

• 2 other identifiers: 21-3000R01DK130255
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

More than 80% of individuals with chronic kidney disease have concomitant hypertension and the majority fail to achieve blood pressure control \<130/80 mmHg, leading to high risk of cardiovascular diseases and end-stage kidney disease. A stepwise combination of lifestyle modifications and drug therapy is recommended to lower blood pressure; however, adherence to time-intensive lifestyle interventions such as aerobic exercise in patients with chronic kidney disease is poor. This clinical trial seeks to establish the efficacy of high-resistance inspiratory muscle strength training, a novel time-efficient lifestyle intervention, for lowering systolic blood pressure and improving endothelial function in midlife and older adults with moderate-to-severe chronic kidney disease and inadequately controlled hypertension, and to use innovate translational assessments to understand the mechanisms involved.

Conditions

Chronic Kidney Diseases; Hypertension; Aging; Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Change in Casual Systolic Blood Pressure

  Casual (resting) measures of systolic blood pressure (mmHg) will be measured in triplicate over the brachial artery of the non-dominant arm after 5 minutes of quiet rest, with 1 minute of recovery between each measure, using an automated oscillometric sphygmomanometer.

  Baseline, 3 months

Secondary Outcomes (2)

• Change in 24-Hour Ambulatory Systolic Blood Pressure

  Baseline, 3 months

• Change in Brachial Artery Flow-Mediated Dilation

  Baseline, 3 months

Other Outcomes (19)

• Change in Ex Vivo Nitric Oxide Production

  Baseline, 3 months

• Change in Ex Vivo HUVEC eNOS Activation

  Baseline, 3 months

• Change in Ex Vivo Reactive Oxygen Species Production

  Baseline, 3 months

Study Arms (2)

IMST

EXPERIMENTAL

This group will perform high-resistance (75% of maximal inspiratory pressure) inspiratory muscle strength training (IMST), 30 inhalations/session, 6 days/week.

Device: IMST

Control

SHAM COMPARATOR

This group will perform low-resistance (15% of maximal inspiratory pressure) inspiratory muscle strength training, 30 inhalations/session, 6 days/week.

Device: Sham Training

Interventions

IMST DEVICE

Inspiratory muscle strength training (IMST) is a form of physical training that utilizes the diaphragm and accessory respiratory muscles to repeatedly inhale against resistance using a handheld device.

IMST

Sham Training DEVICE

Repeated inhalations against a low resistance will be performed using a handheld device.

Control

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 50 years or older; women must be post-menopausal
• Chronic kidney disease stage 3 or 4 (estimated glomerular filtration rate with the 4 CKD-EPI 2021 race-free equation: 20-59 mL/min/1.73m\^2; stable renal function in the past 3 months)
• History of inadequately controlled hypertension (systolic blood pressure 120-159 mmHg on two separate days) and on a stable antihypertensive regimen for the past 6 weeks
• Weight stable in the prior 3 months (\<2 kg weight change) and willing to remain weight stable throughout the study. Participants using glucagon-like peptide-1 receptor agonists or planning to start them during the study are excluded unless they have achieved weight stability for at least 3 months prior to enrollment.
• Ability to provide informed consent

You may not qualify if:

• Patients with advanced chronic kidney disease requiring chronic dialysis
• Significant pulmonary disorders including: chronic obstructive pulmonary disease, interstitial lung disease, cystic fibrosis, or uncontrolled asthma
• History of spontaneous pneumothorax, collapsed lung due to traumatic injury that has not fully healed, burst eardrum that has not fully healed, or other conditions of the eardrum
• Significant co-morbid conditions with a life expectancy of \< 1 year
• History of severe congestive heart failure (i.e., ejection fraction \<35%)
• History of hospitalization within the last month
• Albuminuria (albumin to creatinine ratio \> 2200 mg/g
• Current smoker
• Immunosuppressant agents taken in the past 12 months. Steroids used for the treatment of gout are acceptable; however, patients should not be using steroids within 2 weeks (or 14 days) prior to the vascular testing (rationale: may confound vascular testing)
• Known malignancy
• Inability to cooperate with or clinical contraindication for magnetic resonance imaging including: severe claustrophobia, implants, devices, or non-removable body piercings (these individuals can participate in the study but are excluded from the MRI procedure)
• Illicit drug use or alcohol dependence/abuse, which in the opinion of the investigators, would prohibit compliance with the study intervention

Sponsors & Collaborators

• University of Colorado, Denver: lead
• University of Colorado, Boulder: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Colorado - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Related Publications (2)

• Oh ES, Opoku G, Darvish S, Craighead DH, Ostrow A, Rossman MJ, Steele CN, Struemph T, You Z, Seals DR, Chonchol M, Nowak KL. Sex Differences in Dementia and Mild Cognitive Impairment in Nondialysis CKD. Clin J Am Soc Nephrol. 2025 Nov 20. doi: 10.2215/CJN.0000000922. Online ahead of print. No abstract available.

  PMID: 41264372 DERIVED

• Kistler BM, Kirkman DL, Kusni D, Martin Alemany G, Ribeiro HS, Tarca B, Thompson S, Viana JL, Wilkinson TJ, Wilund KR. Physical Activity and Exercise for Cardiometabolic Health and Fitness in CKD: An Overview by Exercise Type. Clin J Am Soc Nephrol. 2025 Jun 12. doi: 10.2215/CJN.0000000784. Online ahead of print.

  PMID: 40504623 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hypertension

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Kristen Nowak, PhD, MPH

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Michel Chonchol, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristen Nowak, PhD, MPH

CONTACT

303-724-4842; Kristen.Nowak@cuanschutz.edu

Emily Andrews

CONTACT

303-724-7790

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: June 3, 2021
• Study Start: March 1, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).

Locations

US (1)