Applying pGz in Mitochondrial Disease

NCT05569122 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 21-018532
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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).

Conditions

Mitochondrial Myopathies; Mitochondrial Diseases

Keywords

Passive Exercise; periodic acceleration

Outcome Measures

Primary Outcomes (3)

• Aim 1: Mean Difference in Maximal Oxygen Consumption between primary mitochondrial disease patients and healthy volunteers

  Maximal Oxygen Consumption will be measured only during CPET

  During Cardiopulmonary Exercise Testing, which will last 1 hour

• Aim 2: Arterial-Venous (A-V) O2 difference

  This will be measured through blood draws that occur before and after study interventions

  A total of 4 15 minute blood draws

• Aim 1 and 2: Oxygen Consumption

  Measured During the study interventions

  1 hour per study intervention

Secondary Outcomes (9)

• Aim 1 and 2: A/B ratio measurement through EKG or Plethsymography

  1 hour per study intervention

• Aim 1 and 2: Heart Rate

  1 hour per study intervention

• Aim 1 and 2: OXPHOS Capacity

  Aim 1 subjects will complete 2 1 hour MRIs, Aim 2 Subjects will complete 1 1-hour MRI

• Aim 1 and 2: Plasma Lactate Levels

  15 minute blood draws that occur pre and and immediately after each study intervention

• Aim 1 and 2: Vasodilatation

  30 minute ultrasound that occurs pre and immediately after each study intervention

Study Arms (3)

Aim 1: Primary Mitochondrial Disease Patients

EXPERIMENTAL

The participant has the interventions/study visits occur in a random order: CPET pGz administration through pGz Bed pGz administration through Gentle Jogger

Diagnostic Test: Cardiopulmonary Exercise Testing; Device: pGz Bed; Device: Gentle Jogger; Drug: Lumason® contrast agent

Aim 1: Healthy Controls

EXPERIMENTAL

The participant has the interventions/study visits occur in a random order: pGz administration through Gentle Jogger CPET pGz administration through pGz Bed

Diagnostic Test: Cardiopulmonary Exercise Testing; Device: pGz Bed; Device: Gentle Jogger; Drug: Lumason® contrast agent

Aim 2: PICU Patients

EXPERIMENTAL

All participants in Aim 2 will have the interventions/study visits occur in the same order: Exercise Pedal and Gentle Jogger

Device: Gentle Jogger; Device: Exercise Pedal; Drug: Lumason® contrast agent

Interventions

Cardiopulmonary Exercise Testing DIAGNOSTIC_TEST

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

Aim 1: Healthy Controls; Aim 1: Primary Mitochondrial Disease Patients

pGz Bed DEVICE

Participants will lay down on a passive exercise (pGz) bed for 45 minutes during which the bed will administer passive exercise through periodic acceleration

Aim 1: Healthy Controls; Aim 1: Primary Mitochondrial Disease Patients

Gentle Jogger DEVICE

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)

Aim 1: Healthy Controls; Aim 1: Primary Mitochondrial Disease Patients; Aim 2: PICU Patients

Exercise Pedal DEVICE

Participants will exercise while laying down for 20 minutes with an exercise pedal that attaches to the bed

Aim 2: PICU Patients

Lumason® contrast agent DRUG

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.

Aim 1: Healthy Controls; Aim 1: Primary Mitochondrial Disease Patients; Aim 2: PICU Patients

Eligibility Criteria

• Age: 10 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• United States Department of Defense: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (20)

• Sackner MA, Lopez JR, Banderas V, Adams JA. Can Physical Activity While Sedentary Produce Health Benefits? A Single-Arm Randomized Trial. Sports Med Open. 2020 Oct 2;6(1):47. doi: 10.1186/s40798-020-00278-3.

  PMID: 33006749 BACKGROUND

• Sackner MA, Patel S, Adams JA. Changes of blood pressure following initiation of physical inactivity and after external addition of pulses to circulation. Eur J Appl Physiol. 2019 Jan;119(1):201-211. doi: 10.1007/s00421-018-4016-7. Epub 2018 Oct 22.

  PMID: 30350153 BACKGROUND

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• Taivassalo T, Jensen TD, Kennaway N, DiMauro S, Vissing J, Haller RG. The spectrum of exercise tolerance in mitochondrial myopathies: a study of 40 patients. Brain. 2003 Feb;126(Pt 2):413-23. doi: 10.1093/brain/awg028.

  PMID: 12538407 BACKGROUND

• Tarnopolsky M. Exercise testing in metabolic myopathies. Phys Med Rehabil Clin N Am. 2012 Feb;23(1):173-86, xii. doi: 10.1016/j.pmr.2011.11.011. Epub 2011 Dec 11.

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• Tarnopolsky M. Exercise testing as a diagnostic entity in mitochondrial myopathies. Mitochondrion. 2004 Sep;4(5-6):529-42. doi: 10.1016/j.mito.2004.07.011. Epub 2004 Sep 30.

  PMID: 16120411 BACKGROUND

• Taivassalo T, Haller RG. Exercise and training in mitochondrial myopathies. Med Sci Sports Exerc. 2005 Dec;37(12):2094-101. doi: 10.1249/01.mss.0000177446.97671.2a.

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• Adams JA, Uryash A, Bassuk J, Sackner MA, Kurlansky P. Biological basis of neuroprotection and neurotherapeutic effects of Whole Body Periodic Acceleration (pGz). Med Hypotheses. 2014 Jun;82(6):681-7. doi: 10.1016/j.mehy.2014.02.031. Epub 2014 Mar 12.

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• Adams JA, Mangino MJ, Bassuk J, Kurlansky P, Sackner MA. Regional blood flow during periodic acceleration. Crit Care Med. 2001 Oct;29(10):1983-8. doi: 10.1097/00003246-200110000-00022.

  PMID: 11588467 BACKGROUND

• M. Fujita et al., "Periodic acceleration enhances release of nitric oxide in healthy adults," Int. J. Angiol., vol. 14, no. 1, pp. 11-14, Feb. 2005, doi: 10.1007/s00547-005-2013-2.

  BACKGROUND

• Uryash A, Bassuk J, Kurlansky P, Altamirano F, Lopez JR, Adams JA. Antioxidant Properties of Whole Body Periodic Acceleration (pGz). PLoS One. 2015 Jul 2;10(7):e0131392. doi: 10.1371/journal.pone.0131392. eCollection 2015.

  PMID: 26133377 BACKGROUND

• Uryash A, Bassuk J, Kurlansky P, Altamirano F, Lopez JR, Adams JA. Non-invasive technology that improves cardiac function after experimental myocardial infarction: Whole Body Periodic Acceleration (pGz). PLoS One. 2015 Mar 25;10(3):e0121069. doi: 10.1371/journal.pone.0121069. eCollection 2015.

  PMID: 25807532 BACKGROUND

• Adams JA, Patel S, Lopez JR, Sackner MA. The Effects of Passive Simulated Jogging on Short-Term Heart Rate Variability in a Heterogeneous Group of Human Subjects. J Sports Med (Hindawi Publ Corp). 2018 Oct 1;2018:4340925. doi: 10.1155/2018/4340925. eCollection 2018.

  PMID: 30402499 BACKGROUND

• Sackner MA, Gummels E, Adams JA. Nitric oxide is released into circulation with whole-body, periodic acceleration. Chest. 2005 Jan;127(1):30-9. doi: 10.1378/chest.127.1.30.

  PMID: 15653959 BACKGROUND

• Adams JA, Bassuk J, Wu D, Grana M, Kurlansky P, Sackner MA. Periodic acceleration: effects on vasoactive, fibrinolytic, and coagulation factors. J Appl Physiol (1985). 2005 Mar;98(3):1083-90. doi: 10.1152/japplphysiol.00662.2004. Epub 2004 Oct 22.

  PMID: 15501928 BACKGROUND

• Betik AC, Parker L, Kaur G, Wadley GD, Keske MA. Whole-Body Vibration Stimulates Microvascular Blood Flow in Skeletal Muscle. Med Sci Sports Exerc. 2021 Feb 1;53(2):375-383. doi: 10.1249/MSS.0000000000002463.

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• Sjoberg KA, Rattigan S, Hiscock N, Richter EA, Kiens B. A new method to study changes in microvascular blood volume in muscle and adipose tissue: real-time imaging in humans and rat. Am J Physiol Heart Circ Physiol. 2011 Aug;301(2):H450-8. doi: 10.1152/ajpheart.01174.2010. Epub 2011 May 27.

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• Kogan F, Haris M, Debrosse C, Singh A, Nanga RP, Cai K, Hariharan H, Reddy R. In vivo chemical exchange saturation transfer imaging of creatine (CrCEST) in skeletal muscle at 3T. J Magn Reson Imaging. 2014 Sep;40(3):596-602. doi: 10.1002/jmri.24412. Epub 2013 Oct 31.

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• DeBrosse C, Nanga RPR, Wilson N, D'Aquilla K, Elliott M, Hariharan H, Yan F, Wade K, Nguyen S, Worsley D, Parris-Skeete C, McCormick E, Xiao R, Cunningham ZZ, Fishbein L, Nathanson KL, Lynch DR, Stallings VA, Yudkoff M, Falk MJ, Reddy R, McCormack SE. Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders. JCI Insight. 2016 Nov 3;1(18):e88207. doi: 10.1172/jci.insight.88207.

  PMID: 27812541 BACKGROUND

• Jeppesen TD, Schwartz M, Olsen DB, Wibrand F, Krag T, Duno M, Hauerslev S, Vissing J. Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain. 2006 Dec;129(Pt 12):3402-12. doi: 10.1093/brain/awl149. Epub 2006 Jun 30.

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MeSH Terms

Conditions

Mitochondrial Myopathies; Mitochondrial Diseases

Interventions

Exercise Test

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques

Study Officials

• Zuela Zolkipli-Cunningham, MBChB, MRCP

  Attending Physician

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katelynn Stanley, BS

CONTACT

215-426-0225; stanleyk2@chop.edu

Daniel McGinn, MSGC

CONTACT

215-590-1000; mcginnde@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: October 6, 2022
• Study Start: March 22, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (1)