The Effect of Alpha Lipoic Acid on the Incidence and Severity of Radiotherapy-Induced Oral Mucositis in Head and Neck Cancer Patients

NCT05023863 | Unknown Phase 2

• 1 other identifier: PHLCLINICAL
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective, randomized, controlled, single-blinded study will be conducted at Clinical Oncology department, Ain Shams University Hospitals, assessing the effect of Alpha Lipoic Acid on the incidence and severity of radiotherapy induced oral mucositis in Head and Neck cancer patients.

Conditions

Radiation-Induced Mucositis

Keywords

Head and Neck cancer; Alpha Lipoic Acid; Mucositis

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of radiation induced oral mucositis

  The patients will be followed up during the whole period of radiation and up to six weeks after radiation to evaluate the incidence and severity of radiation induced mucositis. Severity will be assessed by the oncologist using radiotherapy oncology group criteria (RTOG criteria)

  4 months

Secondary Outcomes (1)

• Time to develop grade III or IV radiation induced oral mucositis:

  4 months

Study Arms (2)

Alpha Lipoic Acid Group (intervention group)

ACTIVE COMPARATOR

35 patients will receive radiation therapy with or without platinum-based chemotherapy in addition to alpha lipoic acid 600 mg tablets twice daily (throughout the radiotherapy period). .

Drug: Alpha Lipoic Acid 600 MG Oral Tablets; Radiation: radiation or concurrent chemoradiation

Control Group

PLACEBO COMPARATOR

35 Patients will receive radiation therapy with or without platinum-based chemotherapy in addition to placebo tablets twice daily (throughout the radiotherapy period)

Other: Placebo tablets; Radiation: radiation or concurrent chemoradiation

Interventions

Alpha Lipoic Acid 600 MG Oral Tablets DRUG

Alpha Lipoic Acid (ALA) is a drug which has been used in treatment of diabetic neuropathy . It act through enhancing nitric oxide-mediated endothelium-dependent vasodilation, thus improving microcirculation in patients with diabetic polyneuropathy. It is considered a safe drug, generally with a daily dose of 200 to 2400 mg/day is considered tolerable without significant side effects. Only gastrointestinal tracts side effects like nausea, vomiting, dyspepsia and abdominal pain have been described in some clinical trials. Also FDA experts confirm its safety and efficacy in humans

Alpha Lipoic Acid Group (intervention group)

Placebo tablets OTHER

placebo tablets of the same generic of active drug which contain all the same ingredients as active tablets except alpha lipoic acid

Control Group

radiation or concurrent chemoradiation RADIATION

radiation or concurrent radiotherapy plus platinum-based chemotherapy

Alpha Lipoic Acid Group (intervention group); Control Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years.
• Diagnosis of stage I, II, III or IV squamous cell carcinoma, nasopharyngeal carcinoma.
• Measurable disease on CT scan at baseline.
• Planned to receive radiotherapy with a total dose 60 grays or more divided on 30 fractions with or without cisplatin (100 mg/m2, administered intravenously every 21 days for three cycles or 40 mg/m2 administered weekly for up to 7 weeks).
• Adequate liver function (liver transaminases level \< 3 times upper normal limits and total bilirubin \< 1.5 times upper normal limits).
• Adequate kidney function (estimated glomerular filtration rate \>60 ml/min).
• Adequate bone marrow function (WBCs count \> 3000 cells/mm3, ANC count \>1500 cells/mm3 and platelets count \> 100,000 cells/mm3).

You may not qualify if:

• ● Diagnosis of Thyroid cancer.
• Presence of other primary cancers.
• Treatment with alpha lipoic acid for any other indication.
• Allergy to alpha lipoic acid.
• Pregnant or lactating women.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ain Shams University

Cairo, Egypt

Location

Related Publications (20)

• Al Abdan M. Alfa-lipoic acid controls tumor growth and modulates hepatic redox state in Ehrlich-ascites-carcinoma-bearing mice. ScientificWorldJournal. 2012;2012:509838. doi: 10.1100/2012/509838. Epub 2012 May 1.

  PMID: 23002387 BACKGROUND

• Bloomer WD, Hellman S. Normal tissue responses to radiation therapy. N Engl J Med. 1975 Jul 10;293(2):80-3. doi: 10.1056/NEJM197507102930206. No abstract available.

  PMID: 1093032 BACKGROUND

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Elsabagh HH, Moussa E, Mahmoud SA, Elsaka RO, Abdelrahman H. Efficacy of Melatonin in prevention of radiation-induced oral mucositis: A randomized clinical trial. Oral Dis. 2020 Apr;26(3):566-572. doi: 10.1111/odi.13265. Epub 2020 Jan 15.

  PMID: 31869853 BACKGROUND

• Gillison ML. Human papillomavirus-related diseases: oropharynx cancers and potential implications for adolescent HPV vaccination. J Adolesc Health. 2008 Oct;43(4 Suppl):S52-60. doi: 10.1016/j.jadohealth.2008.07.002.

  PMID: 18809146 BACKGROUND

• Jung JH, Jung J, Kim SK, Woo SH, Kang KM, Jeong BK, Jung MH, Kim JH, Hahm JR. Alpha lipoic acid attenuates radiation-induced thyroid injury in rats. PLoS One. 2014 Nov 17;9(11):e112253. doi: 10.1371/journal.pone.0112253. eCollection 2014.

  PMID: 25401725 BACKGROUND

• Kim H, Yoo WS, Jung JH, Jeong BK, Woo SH, Kim JH, Kim SJ. Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling. Int J Mol Sci. 2019 Nov 13;20(22):5691. doi: 10.3390/ijms20225691.

  PMID: 31766286 BACKGROUND

• Kim JH, Jeong BK, Jang SJ, Yun JW, Jung MH, Kang KM, Kim TG, Woo SH. Alpha-Lipoic Acid Ameliorates Radiation-Induced Salivary Gland Injury by Preserving Parasympathetic Innervation in Rats. Int J Mol Sci. 2020 Mar 25;21(7):2260. doi: 10.3390/ijms21072260.

  PMID: 32218158 BACKGROUND

• Kusiak A, Jereczek-Fossa BA, Cichonska D, Alterio D. Oncological-Therapy Related Oral Mucositis as an Interdisciplinary Problem-Literature Review. Int J Environ Res Public Health. 2020 Apr 3;17(7):2464. doi: 10.3390/ijerph17072464.

  PMID: 32260309 BACKGROUND

• Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST, Keefe DM. Serum levels of NFkappaB and pro-inflammatory cytokines following administration of mucotoxic drugs. Cancer Biol Ther. 2008 Jul;7(7):1139-45. doi: 10.4161/cbt.7.7.6207. Epub 2008 Apr 29.

  PMID: 18535404 BACKGROUND

• Lott IT, Doran E, Nguyen VQ, Tournay A, Head E, Gillen DL. Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation. Am J Med Genet A. 2011 Aug;155A(8):1939-48. doi: 10.1002/ajmg.a.34114. Epub 2011 Jul 7.

  PMID: 21739598 BACKGROUND

• Mallick S, Benson R, Rath GK. Radiation induced oral mucositis: a review of current literature on prevention and management. Eur Arch Otorhinolaryngol. 2016 Sep;273(9):2285-93. doi: 10.1007/s00405-015-3694-6. Epub 2015 Jun 27.

  PMID: 26116012 BACKGROUND

• Marur S, Forastiere AA. Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment. Mayo Clin Proc. 2016 Mar;91(3):386-96. doi: 10.1016/j.mayocp.2015.12.017.

  PMID: 26944243 BACKGROUND

• Moreira PI, Harris PL, Zhu X, Santos MS, Oliveira CR, Smith MA, Perry G. Lipoic acid and N-acetyl cysteine decrease mitochondrial-related oxidative stress in Alzheimer disease patient fibroblasts. J Alzheimers Dis. 2007 Sep;12(2):195-206. doi: 10.3233/jad-2007-12210.

  PMID: 17917164 BACKGROUND

• Pearman TP, Beaumont JL, Paul D, Abernethy AP, Jacobsen PB, Syrjala KL, Von Roenn J, Cella D. Evaluation of treatment- and disease-related symptoms in advanced head and neck cancer: validation of the national comprehensive cancer network-functional assessment of cancer therapy-head and neck cancer symptom index-22 (NFHNSI-22). J Pain Symptom Manage. 2013 Jul;46(1):113-20. doi: 10.1016/j.jpainsymman.2012.06.004. Epub 2012 Sep 25.

  PMID: 23017622 BACKGROUND

• Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Moller W, Tritschler HJ, Mehnert H. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res. 1999 Sep;31(3):171-9. doi: 10.1080/10715769900300721.

  PMID: 10499773 BACKGROUND

• Sayed R, El Wakeel L, Saad AS, Kelany M, El-Hamamsy M. Pentoxifylline and vitamin E reduce the severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients: a randomized, controlled study. Med Oncol. 2019 Nov 21;37(1):8. doi: 10.1007/s12032-019-1334-5.

  PMID: 31748905 BACKGROUND

• Siddiqui F, Movsas B. Management of Radiation Toxicity in Head and Neck Cancers. Semin Radiat Oncol. 2017 Oct;27(4):340-349. doi: 10.1016/j.semradonc.2017.04.008.

  PMID: 28865517 BACKGROUND

• Sonis ST. Pathobiology of oral mucositis: novel insights and opportunities. J Support Oncol. 2007 Oct;5(9 Suppl 4):3-11.

  PMID: 18046993 BACKGROUND

• Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med. 2004 Feb;21(2):114-21. doi: 10.1111/j.1464-5491.2004.01109.x.

  PMID: 14984445 BACKGROUND

MeSH Terms

Conditions

Head and Neck Neoplasms; Mucositis

Interventions

Thioctic Acid; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids; Physical Phenomena

Central Study Contacts

Bishoy Anwar Rizk-Allah, bachelor

CONTACT

01228016836; bishoyanwar.rezk@pharma.asu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Model Details: A prospective, randomized, controlled, single blinded study

Study Record Dates

• First Submitted: August 1, 2021
• First Posted: August 27, 2021
• Study Start: September 1, 2021
• Primary Completion: May 1, 2022
• Study Completion: August 1, 2022
• Last Updated: August 27, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)