Understanding the Effects of Pulmonary Arterial Hypertension on Lean Muscle Mass-Substudy (MUSCLE-UPSUB)
Understanding the Effects of Pulmonary Arterial Hypertension on Lean Muscle Mass-Penn Pilot Low Load Resistance Exercise Training Substudy
Study Overview
Status
Conditions
Detailed Description
After obtaining informed consent, patients will be scheduled for an in-person substudy baseline visit. The subject will have their vital signs checked, will complete the E10 questionnaire, have blood drawn, and will complete exercise testing:
an occlusion device (Kaatsu B2 model) will be applied to the thigh area and a wireless NIRS device (PortaMon, Artinis, The Netherlands) will be applied over their right gastrocnemius muscle and secured with strap. The participant will be seated in a chair and allowed to rest for up to 10 minutes, and then the participant will begin performing seated heel raises. Once comfortable with the maneuver, the occlusion device will be inflated to systolic blood pressure (SBP) + 50 mmHg for 5 minutes and the participant will be asked to resume the seated heel raises. Then the cuff will be deflated at the completion of the 5 minutes. This will be followed by a 10-minute rest period and then repeated (cuff inflation and exercises for another 5 minutes). The occlusion device will then be removed, and the patient will continue wearing the NIRS in the seated position for another 20 minutes to capture the recovery phase.
A post-exercise blood draw will completed during the recovery phase.
A certified exercise physiologist will demonstrate the at-home exercises to the participant and assess their strength level and observe them performing them ensuring proper form and technique. Each exercise will be performed in 3 sets of 15-15-15 repetitions. A handout will be given to the participant to be used as a resource during the 12 +/- 1 week period between visits.
Low-load resistance training exercises:
Seated heel raises: Starting from seated position in a chair, the participant will place both their feet on the floor. Next they will press down with the forefoot and toes to raise their heels up off the floor. Then, they will lower their heels back down and repeat. They will be asked to keep their toes down on the floor the entire time.
Depending on the participant's strength, this exercise will be upgraded to seated heel raises with resistance. Participant will be in seated position on chair and will have a weight placed on their thigh comfortably. Then heel raises will be performed as described above.
The next upgrade to this exercise will be standing double heel raises: Participants will be asked to stand near a wall/counter for balance support as needed. The participant will lift up onto the balls of their feet and then slowly lower their heels back to ground and repeat as needed.
The next upgrade to this exercise will be standing single heel raises: Participants will be asked to stand near a wall/counter for balance support as needed. The participant will lift one leg up, bending at the knee then lift up onto the ball of their foot that's on the ground. The participant will then slowly lower their heel back to the ground and repeat as needed.
Plantar flexion: While sitting on the floor or a mat, the participant will place the band around the ball of their foot and toes and pull back until they feel a gentle stretch. The participant will press down on the band using their ankles but keeping their toes relaxed. Then the participant will press down fully with the toes. To release let the band, the participant will pull the toes up first before releasing the ankle back to start. The band resistance will be upgraded as the participant progresses.
Sit to stand: The participant will start by scooting close to the front of the chair. Next, they will lean forward at their trunk and reach forward with their arms and rise to standing without using their hands to push off from the chair or other object. The participant will use their arms as a counter-balance by reaching forward when in sitting and lowering them as they approach standing.
Depending on patient's progress, this will be upgraded to box squats: with hands out in front of the participant, they will bend forwards at the hips, like they are going to sit back on a chair (get their hips as far away from their ankles as they can) and then return to standing. The participant will not sit; just tap the box with their bum. The participant will use the box or chair below as a target to hit as they squat down.
The next upgrade will be to loaded sit to stands: With the participant sitting on a sturdy chair and holding onto a medicine ball, or a weight, they will keep the weight close to the body. Keeping their back straight, the participant will lean forward at the hips (hip hinge) to get their weight over their feet. Then the participant will stand all the way up tall and make sure to keep their abdominals drawn in during the task.
Once each participant feels comfortable in performing the exercises independently, they will be provided with the resistance bands to go home. Each participant will be instructed to perform these exercises 3 times per week at their discretion and to log their completion in the exercise diary. The participant will then be scheduled for a follow-up visit mirroring the baseline visit at 12-weeks +/- 1 week. At the 12-week visit, the participant will also complete the E10 questionnaire and that will conclude their substudy participation.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Nicole Denney, MS
- Phone Number: 215-615-4156
- Email: nicole.denney@pennmedicine.upenn.edu
Study Contact Backup
- Name: Rebecca Gallagher Research Project Manager, MSEd
- Phone Number: 215-662-4088
- Email: rebecca.lang@pennmedicine.upenn.edu
Study Locations
-
-
Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania Hospital
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Contact:
- Nicole Denney, MS
- Phone Number: 215-294-9755
- Email: Nicole.denney@Pennmedicine.upenn.edu
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Principal Investigator:
- Nadine Al-Namaani, MD
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria: Participating the main MUSCLE UP Study:
- Signed informed consent prior to initiation of any study mandated procedure.
- Male and female patient's ≥ 18 years of age.
- Diagnosis of PAH belonging to one of the following subgroups of Group 1 PH according to the updated clinical classification [Humbert 2022]
- Idiopathic (IPAH)
- Heritable (HPAH)
- Drugs or toxins induced
- Associated (APAH) with one of the following:
- Connective tissue disease;
- Human immunodeficiency virus (HIV) infection;
- Congenital heart disease; or
- Portopulmonary hypertension
- Diagnosis of PAH within 6 months of enrollment or diagnosis of PAH and on stable therapy for 3 months prior to enrollment
- Documented hemodynamic diagnosis of PAH by right heart catheterization (RHC), prior to enrollment showing:
- mPAP > 20 mmHg; and
- PAWP or LVEDP ≤ 15 mmHg
- PVR > 2 Wood units
Exclusion Criteria:
- Prior to enrollment, evidence of moderately severe obstructive ventilator defect with:
- FEV1/FVC ≤ 5th percentile; and
- FEV1 z-score < -2.5
- Prior to enrollment, evidence of severe restrictive defect with
- TLC < 5th percentile
- FEV1 z-score < -4
- More than moderate aortic or mitral valve disease
- LVEF < 40% within 1 year of screening
- Pregnancy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Other: Low resistance exercise intervention
Participants will be asked to perform a series of exercises recommend by the National Institute on Aging Go4Life campaign, namely seated heel raise, plantar flexion, sit to stand, and box squats.
They will wear the portamon device to measure muscle oxygenation and have blood drawn to measure adiponectin before performing the above exercises at home for 12 weeks, and then be measured with the portamon device and undergo another flood draw again after 12 weeks.
|
: The investigators will measure oxy-hemoglobin and deoxyhemoglobin concentration using NIRS applied to the biceps and calf pre- and post- exercise at baseline and Week 12.
Moreover, the investigators will measure time to recovery of oxy-hemglobin post-exercise at baseline and at Week 12. Time Frame: 12 weeks
Other Names:
: The investigators will measure adiponectin levels using a solid phase sandwich ELISA (R&D Systems, Inc., Minneapolis, MN) with a minimum detectable dose of 0.246 ng/mL and intra-assay variations (CV) 2.5%-4.7%.Time Frame: 12 Weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Difference in circulating level of adiponectin (ng/mL) pre- and post-exercise at baseline and at Week 12
Time Frame: 12 Weeks
|
The investigators will measure adiponectin levels using a solid phase sandwich ELISA (R&D Systems, Inc., Minneapolis, MN) with a minimum detectable dose of 0.246 ng/mL and intra-assay variations (CV) 2.5%-4.7%.
|
12 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Measurement of deoxyhemoglobin concentration pre and post-exercise at baseline and Week 12.
Time Frame: 12 weeks
|
The investigators will measure deoxyhemoglobin concentration using NIRS applied to the calf pre- and post-exercise at baseline and Week 12.
|
12 weeks
|
|
Measurement of oxyhemoglobin recovery post exercise at Baseline and Week 12
Time Frame: 12 weeks
|
The investigators will measure the time to recovery of oxyhemoglobin concentration post-exercise using NIRS applied to the calf at baseline and Week 12.
|
12 weeks
|
|
Measurement of oxyhemoglobin concentration pre and post- exercise at baseline and Week 12.
Time Frame: 12 weeks
|
The investigators will measure oxy-hemoglobin concentration using NIRS applied to the calf pre- and post- exercise at baseline and Week 12.
|
12 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Nadine Al-Namaani, MD, University of Pennsylvania
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Hypertension, Pulmonary
- Behavior
- Pulmonary Arterial Hypertension
- Motor Activity
- Investigative Techniques
- Specimen Handling
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Punctures
- Surgical Procedures, Operative
- Blood Specimen Collection
Other Study ID Numbers
- 856202 Substudy
- R01HL173533 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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