Preventive Effect of Acetyl-L-carnitine on Oxaliplatin-induced Peripheral Neuropathy

NCT05601479 | Unknown Phase 2 DMC

• 1 other identifier: NFEC-2022-362
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

With the prolongation of the overall survival time of patients with malignant tumors, the influence of oxaliplatin on the quality of life of patients with malignant tumors has gradually become prominent. Studies have shown that acetyl-L-carnitine can improve the energy metabolism of neurotransmitters and inhibit the release of glutamine in the intersynaptic space to reduce pain. Large-scale clinical studies have approved it as a treatment for diabetic peripheral neuropathy. Some small model studies have also found that acetyl-L-carnitine has a definite therapeutic effect on peripheral neurological lesions induced by chemotherapy. The aim of this study is to investigate the safety and efficacy of acetyl-L-carnitine in the prevention of oxaliplatin-induced peripheral neuropathy. The study was divided into an experimental group and a control group. The experimental group was given acetyl-L-carnitine orally, and the researchers regularly evaluated the symptoms and electrophysiological indicators related to peripheral neuropathy. If there is a severe adverse reaction related to acetyl-L-carnitine, the drug should be discontinued and the symptomatic treatment should be given. After the completion of the study, the statistical calculation and analysis will be used to estimate whether the preventive and therapeutic effect of acetyl-L-carnitine on oxaliplatin-induced peripheral neuropathy was statistically significant.

Conditions

Acetylcarnitine; Chemotherapy-induced Peripheral Neuropathy

Outcome Measures

Primary Outcomes (1)

• Incidence rate of OIPN

  To evaluate the preventive effect of acetyl-L-carnitine on OIPN in patients with gastrointestinal 24 weeks of oxaliplatin-based chemotherapy.

  week 24 after enrollment

Secondary Outcomes (3)

• Severity of OIPN

  week 24 after enrollment

• Time of occurrence

  week12, week 24, week 48 after enrollment

• The prognosis of tumor

  week12, week 24, week 48 after enrollment

Study Arms (2)

Acetyl-L-carnitine group(ALC group)

EXPERIMENTAL

At the beginning of the first chemotherapy of the oxaliplatin regimen, acetyl-L-carnitine 500mg will be given orally three times daily for 24 weeks.

Drug: Acetyl-L-carnitine

Blank Control group

NO INTERVENTION

No drugs for the prevention and treatment of peripheral neuropathy will be given.

Interventions

Acetyl-L-carnitine DRUG

At the beginning of the first chemotherapy of the oxaliplatin regimen, Acetyl-L-carnitine 500mg will be given orally three times daily for 24 weeks. If subjects discontinue oxaliplatin-containing chemotherapy for various reasons (e.g., allergy to oxaliplatin), they will continue taking acetyl-L-carnitine until 24 weeks (unless acetyl-L-carnitine intolerance or other conditions interfere with medication).

Also known as: Chinese Food and Drug Administration H20180021

Acetyl-L-carnitine group(ALC group)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old
• The Eastern Cooperative Oncology Group (ECOG) performance status was 0 or 1
• The predicted survival time was ≥12 months
• Subjects will receive oxaliplatin-containing regimens, including
• mFOLFOX6 scheme Oxaliplatin: 85mg/m2 was infused intravenously for 2 hours, day 1; Leucovorin calcium: 400 mg/m2 was infused intravenously for 2 hours, 1 day; 5 - Fluorouracil: After 400mg/m2 intravenous bolus on day 1, then 1200mg (m2•d) continuous intravenous pump infusion (total 2400mg/m2, infusion 46-48h); Chemotherapy will be performed every 2 weeks for 12 cycles.
• CapeOX scheme Oxaliplatin: 130 mg/m2 was infused intravenously for 2 hours, day 1; capecitabine: 1000 mg/m2 orally, bid, 1-14 days; Chemotherapy will be performed every 3 weeks for 8 cycles.
• FOLFOXIRI scheme Irinotecan: 165 mg/m2 was infused intravenously, day 1; Oxaliplatin:85mg/m2 was infused intravenously, day 1; Leucovorin calcium: 400 mg/m2 was infused intravenously, day 1; 5 - Fluorouracil: The total dose of 5-FU was 2400-3200 mg/m2, and the intravenous infusion lasted for 48 hours, day 1; Chemotherapy will be performed every 2 weeks for 12 cycles.
• Laboratory values within 7 days before enrollment should meet the following criteria:
• Blood routine: neutrophil count (ANC) ≥1.5×109/L, platelet count (PLT) ≥100×109/L, hemoglobin (HGB) ≥80g/L; Liver function: serum total bilirubin (TBIL) ≤ 1.5 times upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal; Renal function: creatinine clearance (CCr) ≥ 50ml/min;
• Patients should voluntarily participant in the study, provide written informed consent, and adhere to protocol-specified visits and procedures.

You may not qualify if:

• Participating in other interventional clinical studies (unless participating in an observational study or in the follow-up phase of an interventional study);
• Hyponatremia, hypokalemia, hyperchloremic acidosis, adrenal failure and adrenocortical insufficiency (Addison's disease), hepatic coma, diabetes mellitus, brain or leptomeningeal metastases;
• Patients who has previously received neurotoxic chemotherapy such as taxanes, vinca alkaloids, or cisplatin and received any other medication specifically for the treatment or prevention of neuropathy;
• Patients with peripheral neuropathy (confirmed by nerve conduction velocity measurements) due to other causes (such as radiation or malignant plexopathy, lumbar or cervical radiculopathy, vitamin B12 deficiency, or diabetes) before chemotherapy;
• History of alcohol dependence or concomitant use of other drugs known to affect serotonin levels;
• Having cardiovascular clinical symptoms or disease that is not well controlled;
• The presence of a mental illness or substance abuse condition that may have affected adherence to trial requirements;
• Women who are pregnant or lactating;
• There are medical history, disease, treatment, or laboratory abnormalities that may interfere with the results of the trial, prevent the participant from participating in the study throughout, or the researcher believes that participation in the study is not in the best interests of the participant.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

Related Publications (3)

• Campone M, Berton-Rigaud D, Joly-Lobbedez F, Baurain JF, Rolland F, Stenzl A, Fabbro M, van Dijk M, Pinkert J, Schmelter T, de Bont N, Pautier P. A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy. Oncologist. 2013;18(11):1190-1. doi: 10.1634/theoncologist.2013-0061. Epub 2013 Oct 8.

  PMID: 24105751 RESULT

• Hershman DL, Unger JM, Crew KD, Minasian LM, Awad D, Moinpour CM, Hansen L, Lew DL, Greenlee H, Fehrenbacher L, Wade JL 3rd, Wong SF, Hortobagyi GN, Meyskens FL, Albain KS. Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. J Clin Oncol. 2013 Jul 10;31(20):2627-33. doi: 10.1200/JCO.2012.44.8738. Epub 2013 Jun 3.

  PMID: 23733756 RESULT

• Sun Y, Shu Y, Liu B, Liu P, Wu C, Zheng R, Zhang X, Zhuang Z, Deng Y, Zheng L, Xu Q, Jiang B, Ouyang X, Gao J, Xu N, Li X, Jiang S, Liang C, Yao Y. A prospective study to evaluate the efficacy and safety of oral acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy. Exp Ther Med. 2016 Dec;12(6):4017-4024. doi: 10.3892/etm.2016.3871. Epub 2016 Nov 4.

  PMID: 28105133 RESULT

Related Links

• EORTC QLQ-CIPN20
• Common Terminology Criteria for Adverse Events, CTCAE, version 5.0

MeSH Terms

Interventions

Acetylcarnitine

Intervention Hierarchy (Ancestors)

Carnitine; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals

Study Officials

• Chunlin Wang

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chunlin Wang

CONTACT

18826420386; wangchunl03@163.com

Xiwen Zhang

CONTACT

19880898416; zhangxiwen970416@.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This study was an open-label, unblinded study. Both participants were aware of their enrollment status.Scale evaluators, nerve conduction velocity measurement testers during the study did not know the grouping of subjects. The collected data were submitted to statistical experts who were unaware of the group assignments for statistical analysis.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate professor

Study Record Dates

• First Submitted: October 25, 2022
• First Posted: November 1, 2022
• Study Start: November 1, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: November 1, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)