National CounterACT Initiative

Study Overview
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Brief Summary
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The purpose of the study is to determine in vitro effects on mitochondrial function of selected chemical agents in human cells, and assess the capability of a cell-permeable succinate prodrug to attenuate toxic effects The project aims at repurposing this recent pharmaceutical discovery, currently being developed for treatment of toxic exposure, for an expanded indication to treat chemically induced mitochondrial toxicity.

Detailed Description
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The study duration per subject will be approximately 15 minutes to complete the one time blood collection.

Official Title
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Mitochondrial Targeted Biofuels as Countermeasures Against Chemical Threats

Conditions
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Mitochondrial Alteration

Participation Criteria
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Eligibility Criteria
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Patient Inclusion Criteria: Males or females age greater or equal 2 years of age Weight greater or equal to 10 kg Parental/guardian permission (informed consent) and if appropriate, child assent. Patient Exclusion Criteria: Known primary mitochondrial disorder. Use of an investigational drug within 30 days prior to enrollment. Parents/guardians or subjects who in the opinion of the Investigator, may be non-compliant with study schedules or procedures. Volunteer Inclusion Criteria Males or females > 18 years of age Employee, trainee, or student informed consent Volunteer Exclusion Criteria: Prior enrollment in this study. Known primary mitochondrial disorder. Use of an investigational drug within 30 days prior to enrollment.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient<br>patients scheduled for elective surgery who are patients either as an inpatient or arriving to the hospital on the day of scheduled surgery | |
| Volunteer<br>Volunteers who are employees, trainees and students at the Children's Hospital of Philadelphia (CHOP) will be introduced to the study via an informational study flyer to determine eligibility and desire to participate in the study | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attenuation by the succinate prodrug of toxin-induced decrease in mitochondrial respiration. | Data will be assessed using 2-tailed Student's t-test. Dose-response curves for respiration will be made for each toxin and IC50 calculated. In case of difficulties in demonstrating acute toxicity of chemical agents, dose-titration experiments and long-term incubation (up to 24 hours) will be performed | by end of 2018 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attenuation of toxin-induced decrease in mitochondrial membrane potential and attenuate lactate production by the succinate prodrug. | Data will be assessed using 2-tailed Student's t-test. Dose-response curves for respiration will be made for each toxin and IC50 calculated. In case of difficulties in demonstrating acute toxicity of chemical agents, dose-titration experiments and long-term incubation (up to 24 h) will be performed | by end of 2018 |