Colorectal cancer (CRC) represents one of the most common cancers worldwide and 5-Fluorouracil (5-FU) is still the mainstay of treatment. However, 5-FU is often implicated in inducing oral mucositis (OM), a painful inflammatory condition that may hinder oral intake, negatively impact quality of life and disrupt adherence with cancer treatment.
Oxidative stress and inflammation play a vital role in OM pathogenesis. Alpha-lipoic acid (ALA) is a powerful antioxidant and anti-inflammatory agent that has demonstrated protective effects towards chemotherapy-induced mucosal damage in preclinical studies.
Therefore, ALA may be a promising strategy to minimize or avoid 5-FU-induced oral mucositis in patients with colorectal cancer, which deserves additional clinical investigation.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
ALA Group: patients will receive Alpha lipoic acid 600mg oral tablet twice daily for 6 months
interventionNames
Drug: alpha lipoic acid 600 mg twice daily
type
PLACEBO_COMPARATOR
label
Control group
description
Control group will receive identical placebo oral tablet twice daily for 6 months
interventionNames
Other: Placebo Tablet
Primary outcomes (1)
measure
Serum levels of malondialdehyde (MDA)
timeFrame
6 months
Eligibility
Eligibility (as posted)
Sex
All
Minimum age
18 Years
Show eligibility criteria text
Inclusion Criteria:
1. Age \>18 years.
2. Newly diagnosed chemotherapy naive CRC patients
3. Planned to receive FOLFOX-6 protocol as adjuvant, neoadjuvant or palliative therapy.
4. Adequate liver function (liver transaminases level \< 3 times upper normal limits and total bilirubin \< 1.5 times upper normal limits).
5. Adequate kidney function (estimated glomerular filtration rate \>60 ml/min).
6. Adequate bone marrow function (WBCs count \> 3000 cells/mm3, ANC count \>1500 cells/mm3 and platelets count \> 100,000 cells/mm3).
Exclusion Criteria:
1. Presence of other primary cancers.
2. Treatment with ALA for any other indication.
3. Allergy to ALA.
4. Pregnant or lactating women.
5. Patients with previous mucositis for any reason.
6. Patients who cannot tolerate oral intake.
7. Patients receiving other dietary antioxidant supplements.
References
Publications (37)
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BACKGROUNDSonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB; Mucositis Study Section of the Multinational Association for Supportive Care in Cancer; International Society for Oral Oncology. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004 May 1;100(9 Suppl):1995-2025. doi: 10.1002/cncr.20162. PMID 15108222
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description
serum level of MDA (oxidative stress biomarker) will be assessed at baseline, after 3 months and after 6 months
Secondary outcomes (8)
measure
Incidence of 5FU-induced oral mucositis
timeFrame
6 months
description
the number of patients who will develop oral mucositis will be recorded
measure
Time to develop grade 2 or more Oral Mucositis
timeFrame
6 months
description
Time in days from the start of chemotherapy till the first appearance of grade 2 or more mucositis will be recorded for each patient
measure
Duration of grade 3 or 4 Oral Mucositis
timeFrame
6 months
description
the time in days from the start of chemotherapy till the patient will develop grade 3 or 4 oral mucositis
measure
Number of participants with dose delay/ reduction in chemotherapy due to Oral Mucositis development.
timeFrame
6 months
measure
Assessment of pain score.
timeFrame
6 months
description
patients' level of pain will be assessed using visual analogue scale each cycle as the minimum value is zero which means no pain and the maximum value is 10 which means the worst pain level (higher scores mean a worse outcome )
measure
Assessment of serum levels of Interleukin 1β (IL-1β).
timeFrame
6 months
description
serum level of Interleukin 1β (IL-1β) will be measured at baseline and after 3 months then after 6 months
measure
Patient's quality of life using Patient-Reported Oral Mucositis Symptom (PROMS) scale
timeFrame
6 months
description
the quality of life will be assessed at baseline , after 3 months and after 6 months using Patient-Reported Oral Mucositis Symptom (PROMS) scale, this is a self-administered scale assessing the effect of oral mucositis pain on the patients' activities' in this scale, the minimum score is zero and the maximum score is 100 A patient with a high score reflects greater pain, increased functional impairment, and poorer well-being, while a low score indicates milder or absent mucositis symptoms and better oral function / quality of life.
measure
the safety of ALA
timeFrame
6 months
description
the incidence of adverse effects that will occur during the study will be recorded
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BACKGROUNDLee EY, Lee CK, Lee KU, Park JY, Cho KJ, Cho YS, Lee HR, Moon SH, Moon HB, Yoo B. Alpha-lipoic acid suppresses the development of collagen-induced arthritis and protects against bone destruction in mice. Rheumatol Int. 2007 Jan;27(3):225-33. doi: 10.1007/s00296-006-0193-5. Epub 2006 Aug 31. PMID 16944157
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BACKGROUNDHsieh RY, Huang IC, Chen C, Sung JY. Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review. Nutrients. 2023 Aug 18;15(16):3634. doi: 10.3390/nu15163634. PMID 37630823
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