## Protocol Section
### Identification Module
**NCT ID:** NCT03924479

**Brief Title:** Respiratory Muscle Function in Heart Failure

**Official Title:** Respiratory Muscle-mediated Neural and Cardiovascular Consequences in Heart Failure With Preserved Ejection Fraction

#### Organization Study ID Info
**ID:** 17-007785
#### Organization
**Class:** OTHER
**Full Name:** Mayo Clinic
### Status Module
#### Completion Date
**Date:** 2024-03-21

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-03-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-03-21

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2024-03-21

**Type:** ACTUAL

#### Start Date
**Date:** 2018-11-28

**Type:** ACTUAL

**Status Verified Date:** 2024-03

#### Study First Post Date
**Date:** 2019-04-23
**Type:** ACTUAL
**Study First Submit Date:** 2019-02-04
**Study First Submit QC Date:** 2019-04-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Mayo Clinic

#### Responsible Party

**Investigator Affiliation:** Mayo Clinic

**Investigator Full Name:** Thomas P. Olson, M.S., Ph.D.

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study is being done because investigators are trying to determine how respiratory muscle and lung function influence the exercise responses in heart failure and healthy participants. Further, the heart failure patients will participate in an intervention to improve their respiratory muscle function to determine if this improves exercise capacity.

**Detailed Description:** The participants enrolled in this study will be asked to make 4 or 9 separate study visits. Healthy participants will perform 4 study visits and heart failure participants will perform 9 study visits.

During study visit 1, the participants will be asked to get a DEXA bone scan, perform pulmonary function tests, and exercise on a stationary bike at maximal exertion while breathing into a mouth piece. During the exercise test, a iodine-based dye will be injected via a venous catheter in the arm. Also, a thin balloon will be inserted through the nose into the esophagus.

During study visit 2, the participants will breathe the same way they did during exercise, but will be seated and not exercising. A thin balloon will be inserted through the nose into the esophagus.

During study visits 3 and 4, the participants will perform different respiratory muscle workouts at rest that will be at different intensities ranging from very easy to moderate for \~10 minutes. An iodine-based dye will be injected via a venous catheter in the arm.

The participant's with heart failure will then perform 8 weeks of breathing muscle training at home. After 3 weeks of breathing muscle training, the participants will return for study visit 5 where the training load will be adjusted. Following the 8 weeks of breathing muscle training, the heart failure participants will perform the same 4 study visits as outlined above.

### Conditions Module

**Conditions:**

- Heart Failure, Diastolic

**Keywords:**

- heart failure preserved ejection fraction

- exercise

- respiratory muscle

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- PARTICIPANT

**Primary Purpose:** OTHER

#### Enrollment Info

**Count:** 30

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** The breathing muscle training will consist of 7 sessions per week (1 per day) for 8 weeks. Each training session will consist of breathing \~15 times each minute for 30 minutes at 40% of maximal breathing muscle strength, while using the breathing muscle trainer. During the inhalation, participants will be instructed to inhale as fast as they can, while exhalations will be performed at the participants discretion.

**Intervention Names:**

- Device: PowerBreathe (Breathing muscle training)

**Label:** Breathing muscle training

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** The breathing muscle training will consist of 7 sessions per week (1 per day) for 8 weeks. Each training session will consist of breathing \~15 times each minute for 30 minutes at 2%% of maximal breathing muscle strength, while using the breathing muscle trainer. During the inhalation, participants will be instructed to inhale as fast as they can, while exhalations will be performed at the participants discretion.

**Intervention Names:**

- Device: PowerBreathe (Breathing muscle training)

**Label:** Sham breathing muscle training

**Type:** SHAM_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Breathing muscle training

- Sham breathing muscle training

**Description:** The breathing muscle breathing training will consist of using the PowerBreathe training for 8 weeks. The PowerBreathe is an inspiratory pressure threshold trainer.The valve blocks the airflow until the threshold pressure is achieved by breathing in forcefully into the device.

**Name:** PowerBreathe (Breathing muscle training)

**Other Names:**

- PowerBreathe Device

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Breathing muscle oxygen uptake between heart failure and healthy participants

**Measure:** Breathing muscle oxygen cost

**Time Frame:** Year 1

**Description:** Breathing muscle blood flow between heart failure and healthy participants

**Measure:** Respiratory muscle blood flow

**Time Frame:** Year 1

**Description:** Respiratory muscle workout-induced increases in systolic and diastolic blood pressure between heart failure and healthy participants

**Measure:** Systolic and diastolic blood pressure

**Time Frame:** Year 1

**Description:** Breathing muscle oxygen uptake from pre to post-breathing muscle training in heart failure participants

**Measure:** Breathing muscle oxygen cost

**Time Frame:** Year 2

**Description:** Breathing muscle blood flow rom pre to post-breathing muscle training in heart failure participants

**Measure:** Respiratory muscle blood flow

**Time Frame:** Year 2

**Description:** Respiratory muscle workout-induced increases in systolic and diastolic blood pressure from pre to post-breathing muscle training in heart failure participants

**Measure:** Systolic and diastolic blood pressure

**Time Frame:** Year 2

### Eligibility Module

**Eligibility Criteria:** Healthy subjects: Adults (≥21 years of age) in the absence of a history of HFpEF or HFrEF, pulmonary, neurologic, orthopedic, or other diseases affecting the neuromuscular system. Controls will be matched for age and sex.

All HFpEF patients will be managed by their primary care physician or cardiologist with additional review and oversight by Dr. Borlaug (Co-Investigator) prior to enrollment to ensure adequacy of inclusion and exclusion criteria and that participation in exercise testing and resistance exercise training is safe.

Inclusion Criteria for HFpEF, includes:

* Clinical diagnosis of HFpEF.
* Patients with a history stable (no medication changes in past 6 weeks (w/duration of diagnosis \>6 months).
* New York Heart Association class I-III.
* Current non-smokers with \<15 pack year history.
* Non-pregnant women, and individuals who are able to exercise (i.e. without orthopedic limitations or neuromuscular disorders).

Exclusion Criteria for all subjects, includes:

* history of dangerous arrhythmias
* body mass index \>35 kg/m2
* current smokers and/or smoking history \>15 pack years
* pregnant women
* uremia, history of allergy to iodides
* impaired renal function
* creatinine value greater than or equal to 1.3 mg/dL (via clinical record within the past 6 months)
* diagnosis of liver disease
* individuals who are not able to engage in exercise

**Healthy Volunteers:** True

**Minimum Age:** 21 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Rochester

**Country:** United States

**Facility:** Mayo Clinic in Rochester

**State:** Minnesota

**Zip:** 55905

#### Overall Officials

**Official 1:**

**Affiliation:** Mayo Clinic

**Name:** Thomas P Olson

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### See Also Links

**Label:** Mayo Clinic Clinical Trials

**URL:** https://www.mayo.edu/research/clinical-trials

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M9421

- Name: Heart Failure

- Relevance: HIGH

- As Found: Heart Failure

- ID: M27580

- Name: Heart Failure, Diastolic

- Relevance: HIGH

- As Found: Heart Failure, Diastolic

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006333

- Term: Heart Failure

- ID: D000054144

- Term: Heart Failure, Diastolic

### Misc Info Module

- Version Holder: 2024-05-24
