Mitochondrial Diseases, Mitochondrial Myopathies
Conditions
Keywords
Passive Exercise, periodic acceleration
Brief summary
This is a multi-aim study, studying the effects of conventional exercise (measured through Cardiopulomary Exercises Testing or an in-bed pedal exercise) and passive exercise through periodic acceleration (pGz). Aim 1 will focus on the differences between primary mitochondrial disease (PMD) patients and healthy volunteers. Aim 2 is an exploratory aim, which will be studying the effects in patients admitted to the Children's Hospital of Philadelphia Pediatric Intensive Care Unit (PICU).
Detailed description
Aim 1: Primary Mitochondrial Disease Patients and Healthy Controls Individuals will be screened for eligibility for study entry, and answer questions relating to their ability to perform study procedures and their physical activity levels. Individuals who meet study criteria will have 3 study visits, and each study visit will involve a different intervention. At each of these study visits, individuals will complete one of the following interventions: Cardiopulmonary Exercise Testing (CPET), pGz administration through a bed or recliner, and pGz through a device called a Gentle Jogger. While participants will complete all three study visits, the order of the study visits will occur in random order. During the study visits, participants will have blood draws before and after the study intervention, a vascular ultrasound with a Lumason contrast agent before and after the study intervention, and a Creatine Chemical Exchange Saturation Transfer (CrCEST) MRI of the lower leg. Aim 2: Patients in the Pediatric Intensive Care Unit (PICU) Individuals will be screened for eligibility for study entry. Individuals who meet study criteria will have 2 study visits during their admission to the PICU. The first study visit will involve a pedal exercise and the second study visit will involve pGz administration through a device called a Gentle Jogger. During the study visits, participants will have blood draws before and after the study intervention, a vascular ultrasound with a Lumason contrast agent before and after the study intervention, and if able to safely complete, an CrCEST MRI of the lower leg.
Interventions
DIAGNOSTIC_TESTCardiopulmonary Exercise Testing
Testing with an exercise bicycle that is considered standard of care for determination of exercise capacity. Participants will complete about 20 minutes of pedaling in a stationary exercise bike
DEVICEpGz Bed
Participants will lay down on a passive exercise (pGz) bed for 45 minutes during which the bed will administer passive exercise through periodic acceleration
DEVICEGentle Jogger
Participants will have passive exercise delivered through the gentle jogger device for 45 minutes. This may be sitting down (aim 1 participants) or laying down (aim 2 participants)
DEVICEExercise Pedal
Participants will exercise while laying down for 20 minutes with an exercise pedal that attaches to the bed
Contrast agent used during a vascular ultrasound of the upper leg. Will occur at each study visit twice before and after pGz bed, gentle jogger, exercise pedal or CPET. Drug Administration will be through an IV line and take about 5 - 10 minutes.
Sponsors
United States Department of Defense
Children's Hospital of Philadelphia
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Aim 1 will have the 3 study interventions/study visits occur in random order. The interventions will be performed in primary mitochondrial disease patients and healthy controls Aim 2 will have all participants complete the study interventions/visits in the same order. Patients will be from the PICU
Eligibility
Sex/Gender
ALL
Age
10 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Aim 1 Enrollment Criteria Inclusion Criteria for Healthy Controls * Males or females, 10 years to 60 years, with a minimum height for participation of 135 cm * Ambulatory and able to complete routine clinical exercise testing * Willing and able to complete all study procedures * For individuals under the age of 18, parental/guardian permission (informed consent) and as appropriate, child assent * For individuals over the age of 18 the ability to provide informed consent Inclusion Criteria for PMD Patients * Males or females, 10 years to 60 years, with a minimum height for participation of 135 cm * Ambulatory and able to complete routine clinical exercise testing * Willing and able to complete all study procedures * Genetically confirmed mitochondrial myopathy (MM) as defined by a diagnosis of primary mitochondrial disease (PMD) with predominant symptoms of myopathy as expressed by exercise intolerance and muscle weakness and fatigue * Parental/guardian permission (informed consent) and as appropriate, child assent
Exclusion criteria
for All Aim 1 Participants General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aim 1: Mean Difference in Maximal Oxygen Consumption between primary mitochondrial disease patients and healthy volunteers | During Cardiopulmonary Exercise Testing, which will last 1 hour | Maximal Oxygen Consumption will be measured only during CPET |
| Aim 2: Arterial-Venous (A-V) O2 difference | A total of 4 15 minute blood draws | This will be measured through blood draws that occur before and after study interventions |
| Aim 1 and 2: Oxygen Consumption | 1 hour per study intervention | Measured During the study interventions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aim 1 and 2: A/B ratio measurement through EKG or Plethsymography | 1 hour per study intervention | To measure hemodynamic physiologic marker of cardiac output (CO) |
| Aim 1 and 2: Heart Rate | 1 hour per study intervention | To measure hemodynamic physiologic marker of cardiac output (CO) |
| Aim 1 and 2: OXPHOS Capacity | Aim 1 subjects will complete 2 1 hour MRIs, Aim 2 Subjects will complete 1 1-hour MRI | Measured through a CrCEST Leg MRI, which measures creative levels and recovery in the leg |
| Borg Scale | 15 minutes, taken after each study intervention | Participant tolerance to pGz compared to CPET |
| Aim 1 and 2: Vasodilatation | 30 minute ultrasound that occurs pre and immediately after each study intervention | Measured through a vascular ultrasound with contrast |
| NO release | 15 minutes, before and immediately after each study intervention | Measured through Plethsymography |
| Aim 1 and 2: Plasma Lactate Levels | 15 minute blood draws that occur pre and and immediately after each study intervention | Measured through venous blood draws |
| Plasma Nom Levels | 15 minute blood draws that occur pre and immediately after each study intervention | Measured through venous blood draws |
| Post-operative Patient Satisfaction Survey | 15 minutes, taken after each study intervention | Participant tolerance to pGz compared to CPET |
Countries
United States
Contacts
Primary ContactKatelynn Stanley, BS
Backup ContactDaniel McGinn, MSGC
Outcome results
None listed