Applying pGz in Mitochondrial Disease

• Status: Not yet recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Children's Hospital of Philadelphia
• Collaborator: United States Department of Defense

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