RecruitingPhase 1NCT05569122

Applying pGz in Mitochondrial Disease

The Utility of pGz in Primary Mitochondrial Disorders

Sponsor

Children's Hospital of Philadelphia

Enrollment

90 participants

Start Date

Mar 22, 2023

Study Type

INTERVENTIONAL

Conditions

Mitochondrial Diseases MItochondrial Myopathies

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).

Eligibility

Min Age: 10 YearsMax Age: 60 Years

Inclusion Criteria36

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
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
Males or females ages 10 to 23 years (children and adults)
Non-ambulatory
Genetically confirmed mtDNA-PMD
Cooperative and capable of following research procedures
Have cognitive ability to enable cooperation with study procedures
Admitted to the PICU with an anticipated length of stay for >24 hours
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
Males or females ages 10 to 23 years (children and adults)
Non-ambulatory
Genetically confirmed non-PMD neuromuscular diagnosis
Cooperative and capable of following research procedures
Have cognitive ability to enable cooperation with study procedures
Admitted to the PICU with an anticipated length of stay for >24 hours
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
Males or females ages 10 to 23 years (children and adults)
Non-ambulatory
No known genetic diagnosis with healthy pre-morbid status, admitted to PICU
Cooperative and capable of following research procedures
Have cognitive ability to enable cooperation with study procedures
Admitted to the PICU with an anticipated length of stay for >24 hours
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

Exclusion Criteria49

Tracheostomy
Non-ambulatory
Unable to complete routine exercise testing
Diagnosed with or have symptoms of vertigo
Within 1 month of a recent hospital admission for acute illness
Severe co-existing cardiac or pulmonary disease
Cognitive impairment that may preclude ability to comply with study procedures
Pregnant or lactating females
Active alcohol and/or substance abuse
At the discretion of the principal investigator (PI), any medical condition that will interfere with or prevent the safe completion of the study
Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures
Use of investigational agent(s) within 4 weeks
Individuals who are employed by the U.S. Department of Defense, including U.S military personal
Patients with biliary atresia with asplenia or polysplenia.
Patients with prior liver transplant.
Patients with cystic fibrosis.
Patients with chronic lung disease.
Patients with portal vein thrombosis, cavernous transformation of the portal vein or absent portal vein.
Patients with significant heart disease or severe congenital heart disease.
Patients with a history of allergic reaction to Lumason®, sulfur hexafluoride, sulfur hexafluoride lipid microsphere components, or other ingredients in Lumason (polyethylene glycol, distearoylphosphatidlycholine (DSPC), dipalmitoylphosphatidylglycerol sodium (DPPG-Na, palmitic acid) or other components of the ultrasound contrast agent
Any history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic evaluation
Any history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation
Past or current employment involving (or exposure to) a metal grinder (e.g., at a construction worksite)
Claustrophobia or any known medical conditions which can be exacerbated by stress, anxiety, or panic attacks triggered by enclosed spaces
Inability to lie flat in an MRI scanner for up to 45 minutes
Unable to perform sub-maximal ankle dorsiflexion leg exercise during the MRI study
Have cognitive impairment that may preclude ability to comply with study procedures
Have cardiorespiratory instability
Patients in whom are so sick that they will not be able to cooperate with the study procedures
Have clear contraindications to mobilization
Have fixed lower limb deformities/contractures that would prohibit lower extremity exercise
Pregnant or lactating females
Active alcohol and/or substance abuse
At the discretion of the principal investigator (PI), any medical condition that will interfere with or prevent the safe completion of the study
Use of investigational agent(s) within 4 weeks
Individual who are employed by the U.S. Department of Defense, including U.S military personal
Patients with biliary atresia with asplenia or polysplenia.
Patients with prior liver transplant.
Patients with cystic fibrosis.
Patients with chronic lung disease.
Patients with portal vein thrombosis, cavernous transformation of the portal vein or absent portal vein.
Patients with significant heart disease or severe congenital heart disease.
Patients with a history of allergic reaction to Lumason®, sulfur hexafluoride, sulfur hexafluoride lipid microsphere components, or other ingredients in Lumason (polyethylene glycol, distearoylphosphatidlycholine (DSPC), dipalmitoylphosphatidylglycerol sodium (DPPG-Na, palmitic acid) or other components of the ultrasound contrast agent
Any history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic evaluation
Any history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation
Past or current employment involving (or exposure to) a metal grinder (e.g., at a construction worksite)
Claustrophobia or any known medical conditions which can be exacerbated by stress, anxiety, or panic attacks triggered by enclosed spaces
Inability to lie flat in an MRI scanner for up to 45 minutes
Unable to perform sub-maximal ankle dorsiflexion leg exercise during the MRI study

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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

DRUGLumason® contrast agent

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.