Mitochondrial AlterationNCT03597438
National CounterACT Initiative
An observational study of Mitochondrial Alteration, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Alteration
- How many people
- 236 participants
- Where
- 1 siteUnited States
- Study dates
- 7 May 2018to 22 Feb 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients scheduled for elective surgery will be screened for eligibility. Volunteers who are employees, trainees, and students will be screened for eligibility.
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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Mitochondrial Targeted Biofuels as Countermeasures Against Chemical Threats
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.
Read the detailed description
The study duration per subject will be approximately 15 minutes to complete the one time blood collection.
- Conditions
- Mitochondrial Alteration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patient | patients scheduled for elective surgery who are patients either as an inpatient or arriving to the hospital on the day of scheduled surgery | |
| Volunteer | 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 being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: by end of 2018
Secondary outcomes (1)
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
Measured: by end of 2018
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2018
- Study start7 May 2018
- Primary completion18 Apr 2023
- Study completion22 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial AlterationStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 236 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor
- Investigators
- Todd J Kilbaugh, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03597438
- Sponsor's protocol ID
- 18-015056
- Other IDs
- 1R21NS103826-01
- Status last verified
- Feb 2024
- First submitted
- 13 Jul 2018
- Last updated
- 23 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jeevaratnam K, Vidya S, Vaidyanathan CS. In vitro and in vivo effect of methyl isocyanate on rat liver mitochondrial respiration. Toxicol Appl Pharmacol. 1992 Dec;117(2):172-9. doi: 10.1016/0041-008x(92)90234-j.
PubMed 1471148Ehinger JK, Piel S, Ford R, Karlsson M, Sjovall F, Frostner EA, Morota S, Taylor RW, Turnbull DM, Cornell C, Moss SJ, Metzsch C, Hansson MJ, Fliri H, Elmer E. Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency. Nat Commun. 2016 Aug 9;7:12317. doi: 10.1038/ncomms12317.
PubMed 27502960Degli Esposti M. Inhibitors of NADH-ubiquinone reductase: an overview. Biochim Biophys Acta. 1998 May 6;1364(2):222-35. doi: 10.1016/s0005-2728(98)00029-2.
PubMed 9593904Mesnage R, Arno M, Costanzo M, Malatesta M, Seralini GE, Antoniou MN. Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure. Environ Health. 2015 Aug 25;14:70. doi: 10.1186/s12940-015-0056-1.
PubMed 26302742Friedrich T, van Heek P, Leif H, Ohnishi T, Forche E, Kunze B, Jansen R, Trowitzsch-Kienast W, Hofle G, Reichenbach H, et al. Two binding sites of inhibitors in NADH: ubiquinone oxidoreductase (complex I). Relationship of one site with the ubiquinone-binding site of bacterial glucose:ubiquinone oxidoreductase. Eur J Biochem. 1994 Jan 15;219(1-2):691-8. doi: 10.1111/j.1432-1033.1994.tb19985.x.
PubMed 8307034Lim S, Ahn SY, Song IC, Chung MH, Jang HC, Park KS, Lee KU, Pak YK, Lee HK. Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance. PLoS One. 2009;4(4):e5186. doi: 10.1371/journal.pone.0005186. Epub 2009 Apr 13.
PubMed 19365547Hase Y, Tatsuno M, Nishi T, Kataoka K, Kabe Y, Yamaguchi Y, Ozawa N, Natori M, Handa H, Watanabe H. Atrazine binds to F1F0-ATP synthase and inhibits mitochondrial function in sperm. Biochem Biophys Res Commun. 2008 Feb 1;366(1):66-72. doi: 10.1016/j.bbrc.2007.11.107. Epub 2007 Dec 4.
PubMed 18060860Hollingworth RM, Ahammadsahib KI, Gadelhak G, McLaughlin JL. New inhibitors of complex I of the mitochondrial electron transport chain with activity as pesticides. Biochem Soc Trans. 1994 Feb;22(1):230-3. doi: 10.1042/bst0220230. No abstract available.
PubMed 8206238Satoh T, Miyoshi H, Sakamoto K, Iwamura H. Comparison of the inhibitory action of synthetic capsaicin analogues with various NADH-ubiquinone oxidoreductases. Biochim Biophys Acta. 1996 Jan 11;1273(1):21-30. doi: 10.1016/0005-2728(95)00131-x.
PubMed 8573592Gassner B, Wuthrich A, Scholtysik G, Solioz M. The pyrethroids permethrin and cyhalothrin are potent inhibitors of the mitochondrial complex I. J Pharmacol Exp Ther. 1997 May;281(2):855-60.
PubMed 9152394Gunnell D, Eddleston M, Phillips MR, Konradsen F. The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health. 2007 Dec 21;7:357. doi: 10.1186/1471-2458-7-357.
PubMed 18154668Bus JS, Gibson JE. Paraquat: model for oxidant-initiated toxicity. Environ Health Perspect. 1984 Apr;55:37-46. doi: 10.1289/ehp.845537.
PubMed 6329674Tawara T, Fukushima T, Hojo N, Isobe A, Shiwaku K, Setogawa T, Yamane Y. Effects of paraquat on mitochondrial electron transport system and catecholamine contents in rat brain. Arch Toxicol. 1996;70(9):585-9. doi: 10.1007/s002040050316.
PubMed 8831909Eckerman I. THE BHOPAL SAGA: Universities Press (India); 2005.
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mitochondrial Targeted Biofuels as Countermeasures Against Chemical Threats
- ClinicalTrials.gov ID
- NCT03597438
- Acronym / sponsor ID
- 18-015056
- Conditions
- Mitochondrial Alteration
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 236 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 7 May 2018 (actual)
- Primary completion
- 18 Apr 2023 (actual)
- Study completion
- 22 Feb 2024 (actual)
- First posted
- 24 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
The study duration per subject will be approximately 15 minutes to complete the one time blood collection.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patient | – | –patients scheduled for elective surgery who are patients either as an inpatient or arriving to the hospital on the day of scheduled surgery |
| Volunteer | – | –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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients scheduled for elective surgery will be screened for eligibility. Volunteers who are employees, trainees, and students will be screened for eligibility.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Attenuation by the succinate prodrug of toxin-induced decrease in mitochondrial respiration.
Time frame: by end of 2018
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
1 secondary outcome
Attenuation of toxin-induced decrease in mitochondrial membrane potential and attenuate lactate production by the succinate prodrug.
Time frame: by end of 2018
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
- Background: PubMed 1471148Jeevaratnam K, Vidya S, Vaidyanathan CS. In vitro and in vivo effect of methyl isocyanate on rat liver mitochondrial respiration. Toxicol Appl Pharmacol. 1992 Dec;117(2):172-9. doi: 10.1016/0041-008x(92)90234-j.
- Background: PubMed 27502960Ehinger JK, Piel S, Ford R, Karlsson M, Sjovall F, Frostner EA, Morota S, Taylor RW, Turnbull DM, Cornell C, Moss SJ, Metzsch C, Hansson MJ, Fliri H, Elmer E. Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency. Nat Commun. 2016 Aug 9;7:12317. doi: 10.1038/ncomms12317.
- Background: PubMed 9593904Degli Esposti M. Inhibitors of NADH-ubiquinone reductase: an overview. Biochim Biophys Acta. 1998 May 6;1364(2):222-35. doi: 10.1016/s0005-2728(98)00029-2.
- Background: PubMed 26302742Mesnage R, Arno M, Costanzo M, Malatesta M, Seralini GE, Antoniou MN. Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure. Environ Health. 2015 Aug 25;14:70. doi: 10.1186/s12940-015-0056-1.
- Background: PubMed 8307034Friedrich T, van Heek P, Leif H, Ohnishi T, Forche E, Kunze B, Jansen R, Trowitzsch-Kienast W, Hofle G, Reichenbach H, et al. Two binding sites of inhibitors in NADH: ubiquinone oxidoreductase (complex I). Relationship of one site with the ubiquinone-binding site of bacterial glucose:ubiquinone oxidoreductase. Eur J Biochem. 1994 Jan 15;219(1-2):691-8. doi: 10.1111/j.1432-1033.1994.tb19985.x.
- Background: PubMed 19365547Lim S, Ahn SY, Song IC, Chung MH, Jang HC, Park KS, Lee KU, Pak YK, Lee HK. Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance. PLoS One. 2009;4(4):e5186. doi: 10.1371/journal.pone.0005186. Epub 2009 Apr 13.
- Background: PubMed 18060860Hase Y, Tatsuno M, Nishi T, Kataoka K, Kabe Y, Yamaguchi Y, Ozawa N, Natori M, Handa H, Watanabe H. Atrazine binds to F1F0-ATP synthase and inhibits mitochondrial function in sperm. Biochem Biophys Res Commun. 2008 Feb 1;366(1):66-72. doi: 10.1016/j.bbrc.2007.11.107. Epub 2007 Dec 4.
- Background: PubMed 8206238Hollingworth RM, Ahammadsahib KI, Gadelhak G, McLaughlin JL. New inhibitors of complex I of the mitochondrial electron transport chain with activity as pesticides. Biochem Soc Trans. 1994 Feb;22(1):230-3. doi: 10.1042/bst0220230. No abstract available.
- Background: PubMed 8573592Satoh T, Miyoshi H, Sakamoto K, Iwamura H. Comparison of the inhibitory action of synthetic capsaicin analogues with various NADH-ubiquinone oxidoreductases. Biochim Biophys Acta. 1996 Jan 11;1273(1):21-30. doi: 10.1016/0005-2728(95)00131-x.
- Background: PubMed 9152394Gassner B, Wuthrich A, Scholtysik G, Solioz M. The pyrethroids permethrin and cyhalothrin are potent inhibitors of the mitochondrial complex I. J Pharmacol Exp Ther. 1997 May;281(2):855-60.
- Background: PubMed 18154668Gunnell D, Eddleston M, Phillips MR, Konradsen F. The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health. 2007 Dec 21;7:357. doi: 10.1186/1471-2458-7-357.
- Background: PubMed 6329674Bus JS, Gibson JE. Paraquat: model for oxidant-initiated toxicity. Environ Health Perspect. 1984 Apr;55:37-46. doi: 10.1289/ehp.845537.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Todd J Kilbaugh, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mitochondrial Alteration, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Attenuation by the succinate prodrug of toxin-induced decrease in mitochondrial respiration. (time frame: by end of 2018). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03597438, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2024.