National CounterACT Initiative

NCT ID: NCT03597438

Last Updated: 2024-02-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

236 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-05-07

Study Completion Date

2024-02-22

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.

Conditions

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Mitochondrial Alteration

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Patient

patients scheduled for elective surgery who are patients either as an inpatient or arriving to the hospital on the day of scheduled surgery

No interventions assigned to this group

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

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Males or females age greater or equal 2 years of age
2. Weight greater or equal to 10 kg
3. Parental/guardian permission (informed consent) and if appropriate, child assent.


1. Males or females \> 18 years of age
2. Employee, trainee, or student informed consent

Exclusion Criteria

1. Known primary mitochondrial disorder.
2. Use of an investigational drug within 30 days prior to enrollment.
3. Parents/guardians or subjects who in the opinion of the Investigator, may be non-compliant with study schedules or procedures.


1. Prior enrollment in this study.
2. Known primary mitochondrial disorder.
3. Use of an investigational drug within 30 days prior to enrollment.
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Todd J Kilbaugh, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 1471148 (View on PubMed)

Ehinger 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.

Reference Type BACKGROUND
PMID: 27502960 (View on PubMed)

Degli 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.

Reference Type BACKGROUND
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Mesnage 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.

Reference Type BACKGROUND
PMID: 26302742 (View on PubMed)

Friedrich 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.

Reference Type BACKGROUND
PMID: 8307034 (View on PubMed)

Lim 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.

Reference Type BACKGROUND
PMID: 19365547 (View on PubMed)

Hase 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.

Reference Type BACKGROUND
PMID: 18060860 (View on PubMed)

Hollingworth 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.

Reference Type BACKGROUND
PMID: 8206238 (View on PubMed)

Satoh 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.

Reference Type BACKGROUND
PMID: 8573592 (View on PubMed)

Gassner 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.

Reference Type BACKGROUND
PMID: 9152394 (View on PubMed)

Gunnell 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.

Reference Type BACKGROUND
PMID: 18154668 (View on PubMed)

Bus JS, Gibson JE. Paraquat: model for oxidant-initiated toxicity. Environ Health Perspect. 1984 Apr;55:37-46. doi: 10.1289/ehp.845537.

Reference Type BACKGROUND
PMID: 6329674 (View on PubMed)

Tawara 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.

Reference Type BACKGROUND
PMID: 8831909 (View on PubMed)

Eckerman I. THE BHOPAL SAGA: Universities Press (India); 2005.

Reference Type BACKGROUND

Other Identifiers

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1R21NS103826-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18-015056

Identifier Type: -

Identifier Source: org_study_id

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