A Study of Pulmonary Hypertension Peripheral Limitations

Healthy Clinical Trial

Official title:

Peripheral Limitations in Pulmonary Hypertension and Effects of Muscle Training - The PH Training Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05968859
• Other study ID #: 23-000705
• Secondary ID: 1K23HL164901-01A
• Status: Recruiting
• Phase: N/A
• Start date: January 2, 2024
• Est. completion date: July 2028

Study information

• Verified date: March 2024
• Source: Mayo Clinic
• Contact: Circulatory Failure Research Team
• Phone: (507) 255-2200
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators are doing this research study to compare whole body aerobic training with isolated leg training (with weights) and its impact on effectiveness in symptoms and quality of life in patients with Pulmonary Arterial Hypertension (PAH).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: July 2028
• Est. primary completion date: July 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Pulmonary Arterial Hypertension (PAH) Subjects:

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.

2. NYHA Class II-IV

3. LVEF = 40 % within the preceding year.

4. No hospitalizations due to heart failure in the preceding 30 days.

5. No recent initiation of pulmonary vasodilator in the last 60 days

6. Pulmonary arterial hypertension by right heart catheterization (Mean PA pressure = 20 mmHg with PVR>2 Wood units) with no evidence of heart failure with preserved ejection fraction (exercise PCWP <25 mm Hg).

7. Symptomatic PAH patients with plan to undergo exercise RHC for reassessment of exertional symptoms

2. Healthy Controls:

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.

2. No known diagnosis of heart failure

Exclusion Criteria:

• Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening.

• Planned coronary, carotid, or peripheral artery revascularization.

• Any other condition judged by the investigator to be the primary cause of dyspnea (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g., amyloidosis), hypertrophic obstructive cardiomyopathy, anemia, or more than moderate mitral or aortic heart valve disease).

• Wheelchair bound or orthopedic inability to exercise

• Chronic hypoxemia with inability to exercise without oxygen supplementation (PAH Subjects) or need for oxygen supplementation (Healthy Controls)

• Skeletal muscle myopathy

• History of rhabdomyolysis

• Participation in any clinical trial of an approved or non-approved device for the treatment of pulmonary hypertension within 30 days before screening.

• Receipt of any investigational medicinal product within 30 days before screening

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.

• Major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator.

• Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.

Related Conditions & MeSH terms

• Healthy
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension

Intervention

Behavioral:
• Aerobic Training
Aerobic training will be conducted at 30 minutes 3 times a week using brisk walking with target heart rates goals based on percentage of peak HR reserve (HRR= peak-rest HR) during baseline exercise right heart catheterization (RHC). The target HR will progress over the study period from 50% to 70% of peak HR reserve added to resting HR using the standard Karvonen formula (Goal HR = rest HR + target % of HRR). HR will be monitored using Fitbits to guide training intensity with raw data analyzed using the Fitabase platform to monitor compliance
• Leg Training
Leg training will be performed using assigned ankle weights to perform knee extension while seated. Initial weight assignment will be guided by a protocol driven in-person exercise tolerance test using varying weights to identify the optimal initial and target training weight for each patient based on the 10 repetition maximum weight identified during this test. Leg training weight will begin at 40% of the baseline 10-repetition maximum weight for weeks 1-4 during which time patients will be required to complete 3 sets of 10 repetitions (30 repetitions total) on 3 days per week. For weeks 4-8, 55% of the initial 10-repetition maximum weight will be used for 4 sets of 10 repetitions (40 repetitions total). For weeks 8-12, 70% of the initial 10-repetition maximum weight will be used for 5 sets of 10 repetitions (50 repetitions total).

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in skeletal muscle O2 diffusive conductance (Dm) during supine cycle exercise	Dm is measured in ml/mm Hg/min during supine cycle exercise	Baseline, approximately 12 weeks
Secondary	Change in peak O2 consumption (peak VO2) during supine cycle exercise	Peak VO2 is measured as milliliters of oxygen per kilogram of body weight per minute (ml/kg/min) during supine cycle exercise.	Baseline, approximately 12 weeks
Secondary	Change in skeletal muscle O2 diffusive conductance (Dm) during single knee-extensor exercise	Dm is measured in ml/mm Hg/min during single knee-extensor exercise.	Baseline, approximately 12 weeks
Secondary	Change in maximal mitochondrial respiration	Measured for the respiratory complexes (complex I+II) per mitochondrial protein content (pmol O2/µg mito/sec) from a quadriceps tissue biopsy.	Baseline, approximately 12 weeks
Secondary	Change in Quality of Life as measured by the 36-Item Short-Form Survey (SF-36)	The SF-36 questionnaire measures quality of life through a range of questions asking about patients physical and mental functioning. The SF-36 has a scale of 0-100 with lower scores indicating more disability and lower quality of life.	Baseline, approximately 8 weeks, approximately 12 weeks
Secondary	Change in Quality of Life as measured by the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) questionnaire	PAH-SYMPACT is a PAH-specific patient-reported outcomes instrument that quantifies PAH symptoms and impacts as a measurement of quality of life. The Symptom part is a daily diary that contains 12 items. The respondent is asked to rate each of the items for the past 24 hours. The response options for each item range from 0 " "no [symptom] at all" to 4 "very severe".	Baseline, approximately 8 weeks, approximately 12 weeks
Secondary	Change in Quality of Life as measured by the emPHasis-10 questionnaire	The emPHasis-10 is a short and easy questionnaire that consists of 10 items that address breathlessness, fatigue, control, and confidence. Each item is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end. A total emPHasis-10 score is derived using simple aggregation of the 10 items. emPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life.	Baseline, approximately 8 weeks, approximately 12 weeks