Applying pGz in Mitochondrial Disease

Launched by CHILDREN'S HOSPITAL OF PHILADELPHIA · Oct 3, 2022

Keywords

ClinConnect Summary

This clinical trial, titled "Applying pGz in Mitochondrial Disease," is exploring new ways to help people with mitochondrial diseases, specifically mitochondrial myopathies. The study will compare how conventional exercises and a special type of passive exercise called periodic acceleration (pGz) affect patients with these diseases versus healthy volunteers. The trial has two main goals: the first is to understand the differences in responses between patients with primary mitochondrial diseases (PMD) and healthy individuals, while the second aims to evaluate the effects of these exercises on patients who are in the Pediatric Intensive Care Unit (PICU) at the Children's Hospital of Philadelphia.

To participate, individuals must be between the ages of 10 and 60, able to walk, and have a confirmed diagnosis of mitochondrial myopathy or a related condition. Participants will undergo various exercise tests and procedures throughout the trial, with close monitoring by the study team. It's important to note that there are certain health conditions that might prevent someone from joining, such as severe heart or lung problems. Anyone interested in participating should discuss this opportunity with their healthcare provider to see if it’s a good fit for them.

Gender

ALL

Eligibility 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 Exclusion Criteria
• • 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
• • Aim 2 Enrollment Criteria Inclusion Criteria for PICU PMD Non-Ambulatory Patients
• • 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
• • Inclusion Criteria for PICU non-PMD neuromuscular diagnosis
• • 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
• • Inclusion Criteria for all other PICU Participants
• • 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 Criteria for All Aim 2 Participants
• • 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
• Exclusion Criteria Specific to study procedure: CrCEST MRI Scan:
• • 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