A Pilot Trial to Determine the Effective N-acetylcysteine Dose for Opioid Reduction for Spine Surgery.

NCT ID: NCT04562597

Last Updated: 2023-02-14

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-20

Study Completion Date

2022-05-21

Brief Summary

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Determine the optimal dose of IV N-acetylcysteine (NAC) to produce opioid reduction following spine surgery and estimate the difference in opioid consumption between placebo and the selected optimal dose.

Detailed Description

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First 20 subjects: 5 participants will be randomized to each dose group (placebo, 50, 100, and 150 mg/kg) to estimate the dose response curve and to identify the optimal dose.

If the dose response curve is adequate and the optimal dose identified, 15 additional participants will be randomized to placebo and 15 to the optimal dose to estimate the difference in opioid consumption between participants on placebo vs. the optimal dose. (Total of 50 subjects with 20 from dose response curve and 30 to estimate the difference in opioid consumption.)

If the dose response curve is not adequate after the initial 20 subjects 5 per each dose group, then an additional 5 participants will be randomized and to each dose group (placebo, 50, 100, and 150 mg/kg) to estimate the dose response curve and to identify the optimal dose. Once the optimal dose is identified with these initial 40 patients, 10 additional participants will be randomized to placebo and 10 to the optimal dose to estimate the difference in opioid consumption between participants on placebo vs. the optimal dose. (60 patients total with 40 to create the dose response curve and 20 more to estimate the difference in opioid consumption.)

A sample size of 20 subjects per group (placebo and optimal dose) allows us to estimate a 95% confidence interval for the mean difference in opioid consumption with a width of + 0.64 standard deviations from the mean. 70 subjects may be enrolled to account for withdrawal but the study will be completed once 50 or 60 subjects (based on the number of subjects required to create the dose response curve) have completed the protocol.

Conditions

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Surgery

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

PHASE I. First 20 subjects (4 arms): We will initially randomize 5 patients to each dose group (placebo, 50, 100, and 150 mg/kg) to estimate the dose response curve and to identify the optimal dose. After enrollment of the first 20 patients, the study will undergo review by the study team and statistician.

PHASE II: (2 arms) If the dose response curve is adequate and the optimal dose identified, 15 additional participants will be randomized to placebo and 15 to the optimal dose to estimate the difference in opioid consumption between patients on placebo vs. the optimal dose.

Primary and secondary outcomes will be evaluated only for the placebo and optimal NAC groups.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Dose Response Curve Placebo

5 participants will be randomized to the placebo group to estimate the dose response curve and to identify the optimal dose.

Group Type PLACEBO_COMPARATOR

Dose Response Curve Placebo

Intervention Type DRUG

5 participants will be randomized to the placebo group to estimate the dose response curve and to identify the optimal dose.

Dose Response Curve N-acetylcysteine 50 mg/kg

5 participants will be randomized to the N-acetylcysteine 50 mg/kg group to estimate the dose response curve and to identify the optimal dose.

Group Type ACTIVE_COMPARATOR

Dose Response Curve N-acetylcysteine 50 mg/kg

Intervention Type DRUG

5 participants will be randomized to the N-acetylcysteine 50 mg/kg group to estimate the dose response curve and to identify the optimal dose.

Dose Response Curve N-acetylcysteine 100 mg/kg

5 participants will be randomized to the N-acetylcysteine 100 mg/kg group to estimate the dose response curve and to identify the optimal dose.

Group Type ACTIVE_COMPARATOR

Dose Response Curve N-acetylcysteine 100 mg/kg

Intervention Type DRUG

5 participants will be randomized to the N-acetylcysteine 100 mg/kg group to estimate the dose response curve and to identify the optimal dose.

Dose Response Curve N-acetylcysteine 150 mg/kg

5 participants will be randomized to the N-acetylcysteine 150 mg/kg group to estimate the dose response curve and to identify the optimal dose.

Group Type ACTIVE_COMPARATOR

Dose Response Curve N-acetylcysteine 150 mg/kg

Intervention Type DRUG

5 participants will be randomized to the N-acetylcysteine 150 mg/kg group to estimate the dose response curve and to identify the optimal dose.

Opioid Reduction with Optimal N-acetylcysteine Dose

Once the optimal N-acetylcysteine dose is identified, 15 additional participants will be randomized to the optimal dose to estimate the difference in opioid consumption between patients on placebo vs. the optimal dose. Primary and secondary outcomes will only be evaluated for the placebo group and optimal NAC group.

Group Type ACTIVE_COMPARATOR

Opioid Reduction with Optimal N-acetylcysteine Dose

Intervention Type DRUG

Once the optimal N-acetylcysteinedose is identified, 15 participants will be randomized to the optimal dose (50,100, or 150 mg/kg) to estimate the difference in opioid consumption between patients administered optimal N-acetylcysteine dose or placebo.

Placebo

15 Participants will be randomized to placebo to estimate the difference in opioid consumption between patients on placebo vs. the optimal dose. Primary and secondary outcomes will only be evaluated for the placebo group and optimal NAC group.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

15 Participants will be randomized to placebo to estimate the difference in opioid consumption between patients administered optimal N-acetylcysteine dose or placebo.

Interventions

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Dose Response Curve Placebo

5 participants will be randomized to the placebo group to estimate the dose response curve and to identify the optimal dose.

Intervention Type DRUG

Dose Response Curve N-acetylcysteine 50 mg/kg

5 participants will be randomized to the N-acetylcysteine 50 mg/kg group to estimate the dose response curve and to identify the optimal dose.

Intervention Type DRUG

Dose Response Curve N-acetylcysteine 100 mg/kg

5 participants will be randomized to the N-acetylcysteine 100 mg/kg group to estimate the dose response curve and to identify the optimal dose.

Intervention Type DRUG

Dose Response Curve N-acetylcysteine 150 mg/kg

5 participants will be randomized to the N-acetylcysteine 150 mg/kg group to estimate the dose response curve and to identify the optimal dose.

Intervention Type DRUG

Opioid Reduction with Optimal N-acetylcysteine Dose

Once the optimal N-acetylcysteinedose is identified, 15 participants will be randomized to the optimal dose (50,100, or 150 mg/kg) to estimate the difference in opioid consumption between patients administered optimal N-acetylcysteine dose or placebo.

Intervention Type DRUG

Placebo

15 Participants will be randomized to placebo to estimate the difference in opioid consumption between patients administered optimal N-acetylcysteine dose or placebo.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Undergoing elective spine surgery involving 4 levels or less of the thoracic, lumbar, or sacral spine.
* 18 years of age and older.

Exclusion Criteria

* Less than 40kg in weight.
* Unable to provide written, informed consent.
* History of an adverse or anaphylactoid reaction to acetylcysteine.
* Active asthma, wheezing, or using inhaled bronchodilators.
* Pregnant Women
* Known blood clotting deficiency
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Medical University of South Carolina

OTHER

Sponsor Role lead

Responsible Party

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Sylvia Wilson

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sylvia Wilson, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

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Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Countries

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United States

References

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Hall AJ, Logan JE, Toblin RL, Kaplan JA, Kraner JC, Bixler D, Crosby AE, Paulozzi LJ. Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA. 2008 Dec 10;300(22):2613-20. doi: 10.1001/jama.2008.802.

Reference Type BACKGROUND
PMID: 19066381 (View on PubMed)

Pieralisi A, Martini C, Soto D, Vila MC, Calvo JC, Guerra LN. N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes. Redox Biol. 2016 Oct;9:39-44. doi: 10.1016/j.redox.2016.05.006. Epub 2016 May 27.

Reference Type BACKGROUND
PMID: 27281491 (View on PubMed)

Heim MU, Alraun K, Leeping M, Schwarzfischer G, Bock M, Kling A, Mempel W. [Incidence of the detection of erythrocyte antibodies in relation to screening test cells]. Beitr Infusionsther. 1992;30:443-5. German.

Reference Type BACKGROUND
PMID: 1284756 (View on PubMed)

Guo F, Li Y, Wang J, Li Y, Li Y, Li G. Stanniocalcin1 (STC1) Inhibits Cell Proliferation and Invasion of Cervical Cancer Cells. PLoS One. 2013;8(1):e53989. doi: 10.1371/journal.pone.0053989. Epub 2013 Jan 29.

Reference Type BACKGROUND
PMID: 23382863 (View on PubMed)

Bavarsad Shahripour R, Harrigan MR, Alexandrov AV. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain Behav. 2014 Mar;4(2):108-22. doi: 10.1002/brb3.208. Epub 2014 Jan 13.

Reference Type BACKGROUND
PMID: 24683506 (View on PubMed)

Tardiolo G, Bramanti P, Mazzon E. Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases. Molecules. 2018 Dec 13;23(12):3305. doi: 10.3390/molecules23123305.

Reference Type BACKGROUND
PMID: 30551603 (View on PubMed)

Monti DA, Zabrecky G, Kremens D, Liang TW, Wintering NA, Bazzan AJ, Zhong L, Bowens BK, Chervoneva I, Intenzo C, Newberg AB. N-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease. Clin Pharmacol Ther. 2019 Oct;106(4):884-890. doi: 10.1002/cpt.1548. Epub 2019 Jul 17.

Reference Type BACKGROUND
PMID: 31206613 (View on PubMed)

Monti DA, Zabrecky G, Kremens D, Liang TW, Wintering NA, Cai J, Wei X, Bazzan AJ, Zhong L, Bowen B, Intenzo CM, Iacovitti L, Newberg AB. N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data. PLoS One. 2016 Jun 16;11(6):e0157602. doi: 10.1371/journal.pone.0157602. eCollection 2016.

Reference Type BACKGROUND
PMID: 27309537 (View on PubMed)

Holmay MJ, Terpstra M, Coles LD, Mishra U, Ahlskog M, Oz G, Cloyd JC, Tuite PJ. N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Clin Neuropharmacol. 2013 Jul-Aug;36(4):103-6. doi: 10.1097/WNF.0b013e31829ae713.

Reference Type BACKGROUND
PMID: 23860343 (View on PubMed)

Coles LD, Tuite PJ, Oz G, Mishra UR, Kartha RV, Sullivan KM, Cloyd JC, Terpstra M. Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress. J Clin Pharmacol. 2018 Feb;58(2):158-167. doi: 10.1002/jcph.1008. Epub 2017 Sep 22.

Reference Type BACKGROUND
PMID: 28940353 (View on PubMed)

Halboub E, Alkadasi B, Alakhali M, AlKhairat A, Mdabesh H, Alkahsah S, Abdulrab S. N-acetylcysteine versus chlorhexidine in treatment of aphthous ulcers: a preliminary clinical trial. J Dermatolog Treat. 2021 Sep;32(6):649-653. doi: 10.1080/09546634.2019.1688231. Epub 2019 Nov 21.

Reference Type BACKGROUND
PMID: 31679408 (View on PubMed)

Li J, Xu L, Deng X, Jiang C, Pan C, Chen L, Han Y, Dai W, Hu L, Zhang G, Cheng Z, Liu W. N-acetyl-cysteine attenuates neuropathic pain by suppressing matrix metalloproteinases. Pain. 2016 Aug;157(8):1711-1723. doi: 10.1097/j.pain.0000000000000575.

Reference Type BACKGROUND
PMID: 27075430 (View on PubMed)

Notartomaso S, Scarselli P, Mascio G, Liberatore F, Mazzon E, Mammana S, Gugliandolo A, Cruccu G, Bruno V, Nicoletti F, Battaglia G. N-Acetylcysteine causes analgesia in a mouse model of painful diabetic neuropathy. Mol Pain. 2020 Jan-Dec;16:1744806920904292. doi: 10.1177/1744806920904292.

Reference Type BACKGROUND
PMID: 32009537 (View on PubMed)

Dludla PV, Nkambule BB, Dias SC, Johnson R. Cardioprotective potential of N-acetyl cysteine against hyperglycaemia-induced oxidative damage: a protocol for a systematic review. Syst Rev. 2017 May 12;6(1):96. doi: 10.1186/s13643-017-0493-8.

Reference Type BACKGROUND
PMID: 28499416 (View on PubMed)

Hoffer BJ, Pick CG, Hoffer ME, Becker RE, Chiang YH, Greig NH. Repositioning drugs for traumatic brain injury - N-acetyl cysteine and Phenserine. J Biomed Sci. 2017 Sep 9;24(1):71. doi: 10.1186/s12929-017-0377-1.

Reference Type BACKGROUND
PMID: 28886718 (View on PubMed)

Howard RJ, Blake DR, Pall H, Williams A, Green ID. Allopurinol/N-acetylcysteine for carbon monoxide poisoning. Lancet. 1987 Sep 12;2(8559):628-9. doi: 10.1016/s0140-6736(87)93018-2. No abstract available.

Reference Type BACKGROUND
PMID: 2887913 (View on PubMed)

Hamamsy ME, Bondok R, Shaheen S, Eladly GH. Safety and efficacy of adding intravenous N-acetylcysteine to parenteral L-alanyl-L-glutamine in hospitalized patients undergoing surgery of the colon: a randomized controlled trial. Ann Saudi Med. 2019 Jul-Aug;39(4):251-257. doi: 10.5144/0256-4947.2019.251. Epub 2019 Aug 5.

Reference Type BACKGROUND
PMID: 31381364 (View on PubMed)

Soleimani A, Habibi MR, Hasanzadeh Kiabi F, Alipour A, Habibi V, Azizi S, Emami Zeydi A, Sohrabi FB. The effect of intravenous N-acetylcysteine on prevention of atrial fibrillation after coronary artery bypass graft surgery: a double-blind, randomised, placebo-controlled trial. Kardiol Pol. 2018;76(1):99-106. doi: 10.5603/KP.a2017.0183. Epub 2017 Oct 5.

Reference Type BACKGROUND
PMID: 28980294 (View on PubMed)

Sins JWR, Fijnvandraat K, Rijneveld AW, Boom MB, Kerkhoffs JH, van Meurs AH, de Groot MR, Heijboer H, Dresse MF, Le PQ, Hermans P, Vanderfaeillie A, Van Den Neste EW, Benghiat FS, Kesse-Adu R, Delannoy A, Efira A, Azerad MA, de Borgie CA, Biemond BJ. Effect of N-acetylcysteine on pain in daily life in patients with sickle cell disease: a randomised clinical trial. Br J Haematol. 2018 Aug;182(3):444-448. doi: 10.1111/bjh.14809. Epub 2017 Jun 23. No abstract available.

Reference Type BACKGROUND
PMID: 28643376 (View on PubMed)

Heidari N, Sajedi F, Mohammadi Y, Mirjalili M, Mehrpooya M. Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy. J Pain Res. 2019 Nov 19;12:3147-3159. doi: 10.2147/JPR.S228255. eCollection 2019.

Reference Type BACKGROUND
PMID: 31819599 (View on PubMed)

Kerr F, Dawson A, Whyte IM, Buckley N, Murray L, Graudins A, Chan B, Trudinger B. The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine. Ann Emerg Med. 2005 Apr;45(4):402-8. doi: 10.1016/j.annemergmed.2004.08.040.

Reference Type BACKGROUND
PMID: 15795719 (View on PubMed)

Yip L, Dart RC. A 20-hour treatment for acute acetaminophen overdose. N Engl J Med. 2003 Jun 12;348(24):2471-2. doi: 10.1056/NEJM200306123482422. No abstract available.

Reference Type BACKGROUND
PMID: 12802041 (View on PubMed)

Wilson SH, Sirianni JM, Bridges KH, Wolf BJ, Valente IE, Scofield MD. The impact of intraoperative N-acetylcysteine on opioid consumption following spine surgery: a randomized pilot trial. Pain Manag. 2023 Oct;13(10):593-602. doi: 10.2217/pmt-2023-0061. Epub 2023 Oct 25.

Reference Type DERIVED
PMID: 37877260 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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Pro00099062

Identifier Type: -

Identifier Source: org_study_id

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