A Phase 2/3 interventional study of alpha lipoic acid 600 mg twice daily and Placebo Tablet in Colorectal Cancer, sponsored by Ain Shams University. Recruiting at 1 site in Egypt. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-30.
Sponsored by Ain Shams University · Phase 2/3, Interventional, and Prevention
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.
Colorectal cancer (CRC) is characterized by abnormal growth of colon or rectum cells. It accounts for approximately 10% of all cancer cases, with the majority of cases occurring in older individuals aged 50 years and above .It is considered the third most common cancer globally (6.1%) after lung cancer in both female and male (11.6%), (breast cancer is the second common cancer in females) (11.6%) and (prostate cancer is the second common in males) (7.1%) .It is estimated that CRC cases will rise by 71.5% among males and by 60% among females by 2035. It stands as the second most common cause of cancer-related mortality worldwide, accounting for 9.2% of all cases (9% male and 8% female).
Surgery remains the primary curative treatment for localized disease and is considered the most definitive treatment for colon cancer, while systemic chemotherapy is utilized across neoadjuvant, adjuvant, and metastatic settings. Commonly used chemotherapy protocols include 5-fluorouracil in combination with oxaliplatin or irinotecan. Hence, 5- fluorouracil (5-FU) is considered the backbone of CRC chemotherapy.
As an analogue of pyrimidine, the mechanism of 5-FU cytotoxicity is via competitive inhibition of thymidylate synthetase with consequent thymidine deficiency resulting in inhibition of deoxyribonucleic acid (DNA) synthesis. In addition, incorporation into ribonucleic acid (RNA) interferes with RNA processing and function.
However, despite its efficacy, the continuous infusion of 5-FU is frequently complicated with many toxicities including neutropenia, hand-foot syndrome (HFS), diarrhea, nausea, vomiting and mucositis due to non-selective cytotoxicity on rapidly dividing cells.
Oral mucositis is a debilitating inflammatory reaction of mucous membrane which is a significant problem in patients undergoing chemotherapeutic management, such as 5-FU. Patients experience symptoms ranging from oral pain and dysphagia to severe diarrhea and malnutrition, significantly compromising quality of life and treatment adherence. These effects can lead to chemotherapy dose modifications or interruption, eventually affecting therapeutic outcomes and contributing to infection-related death, emphasizing the need for effective management strategies. Several risk factors predispose patients to develop mucositis such as old age, female gender, overweight, dihydropyrimidine dehydrogenase deficiency, a critical enzyme for 5-FU catabolism, reduced drug clearance and genetic susceptibility.
While mucositis can affect the entire gastrointestinal tract, OM represents a significant clinical challenge owing to its impact on essential functions including speech, mastication, and swallowing, which disturbs nutritional intake and quality of life in cancer patients. The incidence of oral mucositis (OM) with 5-FU of grades 1 and 2 is nearly 93% in CRC cancers.
The pathophysiology of chemotherapy induced OM is comprised of a complex process of five stages, including initiation, signaling, amplification, ulceration, and healing.
During the initiation phase, tissue injury results in the death of the basal epithelial cells and the generation of reactive oxygen species due to dysfunction in the antioxidant protective pathway enzymes including glutathione (GSH), superoxide dismutase (SOD), catalase, myeloperoxidase (MPO), and hydrogen peroxide thereby leading to oxidative stress. This oxidative stress is associated with elevated levels of malondialdehyde (MDA) and 4-hydroxynonenal, although visible symptoms are absent at this stage.
The signaling phase occurs within hours to several days after the initial insult, where upregulation of pro-apoptotic signaling pathways such as nuclear factor kappa B (NFκB) promotes pro-inflammatory cytokine production such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). In that stage mild erythema becomes evident.
During the signal amplification phase, occurring on days 3-5 depending on the regimen, inflammatory pathways such as TNF-α are amplified causing further cellular damage and death. Additionally, matrix metalloproteinases (MMPs) (especially MMP-1 and MMP-3) are activated, leading to degradation of the extracellular matrix and epithelial connective tissue interface, resulting in increased erythema and soreness.
The ulceration phase typically occurs around day 5-10 after chemotherapy or during the second week of radiotherapy. This phase is characterized by epithelial breakdown resulting in visible painful ulcers covered with a fibrinous pseudo membrane (grayish-white appearance). Bacterial colonization in the ulcer bed activates macrophages, stimulating release of TNF-α, IL-1β, thus exacerbating inflammation.
Finally, the healing phase starts once chemotherapy or radiotherapy is discontinued or completed, during which epithelial proliferation is initiated, thus restoring tissue integrity.
Chemotherapy-induced ROS play a key role in the development of OM, a fact that has led to the evaluation of the oxidative stress pathway as a potential target for OM prevention and management.
Studies investigating oxidative stress and the role of antioxidants, in the context of chemo induced OM, have assessed their effects on mitigating the severity of OM in various settings.
As in previous clinical study reported that curcumin, due to its antioxidant and anti-inflammatory effects, promoted rapid recovery and reduced OM severity in chemotherapy-induced cases.
In another previous clinical study reported that oral zinc sulfate reduces the incidence and severity of chemo induced OM, pain, and dry mouth by its antioxidant effect.
In another previous clinical study reported that silymarin reduced severity and delayed onset of mucositis by its antioxidant effect.
Despite these efforts, no standardized prophylactic therapy has been established. Current management remains mostly supportive, focusing on good oral hygiene, and analgesia.
Alpha-lipoic acid (ALA) (1,2-dithiolane-3-pentanoic acid, ALA) and its reduced form, dihydrolipoic acid (DHLA), are naturally occurring antioxidants found in both plants and animals. Clinically, it is a supplement for managing chronic diseases characterized by oxidative stress, notably diabetic neuropathy, demonstrating promise in slowing the onset of metabolic syndrome through antioxidant properties. The dosage range of ALA that can produce favorable effect is(600mg/day-1800mg/day) without experiencing any harmful adverse effects. The most common adverse effects reported with ALA are headache, heartburn, nausea, and vomiting.
ALA can mitigate ROS production by regenerating endogenous antioxidants such as glutathione, vitamin E, and C, in addition to its metal chelation activity, thus causing significant decline in the serum levels of oxidative stress markers such as MDA. A previous clinical study reported that ALA at a dose 300 mg twice daily for 4 months significantly decreased MDA in type-1 diabetic patients with subclinical left ventricular dysfunction. Another study reported that higher doses of ALA, 600 mg twice daily for 3 months, significantly decreased MDA in patients with non-alcoholic fatty liver disease.
Moreover, ALA exhibited strong anti-inflammatory effects. In a preclinical study, ALA significantly decreased IL-1β in lipopolysaccharide-induced endothelial fractalkine expression. In another study evaluating the protective effect of ALA against bone destruction in mice, ALA significantly decreased IL-1β levels .Moreover, ALA inhibited proinflammatory pathways mediated by NF-κB, TNF-α, and IL-6, while enhancing the activity of the anti-inflammatory protein nuclear factor erythroid 2-related factor 2 (Nrf2), thereby reducing tissue damage .
Due to the previously mentioned benefits, ALA has been suggested as a potential candidate for mucositis prevention. A study that evaluated the protective effects of ALA against 5FU-Induced gastrointestinal mucositis in rats reported that ALA treatment decreased TNF-α/IL-1β, MDA, and (matrix metalloproteinases) MMPs/TIMP-1( tissue inhibitor of metalloproteinases 1), while it increased SOD (superoxide dismutase) and GPx (glutathione peroxidase) compared to untreated controls ,ALA also ameliorated severe mucosal damage (degeneration of epithelial cells, edema, villus irregularities) in stomach and small intestine.
In a rat model of methotrexate induced oral mucositis, ALA significantly decreased MDA levels while restoring the antioxidant defense system by increasing activities of SOD and catalase, along with elevated GSH compared to the control group. ALA also markedly reduced the expression of TNF-α and caspase-3 expression in oral epithelial cells and improved histological appearance of the mucosa with less tissue degeneration and fewer ulcerations. Therefore, ALA, might be a potential protective agent against 5-FU-induced mucositis in CRC patients, by mitigating oxidative stress and inflammation.
6,541 studies on the registry are indexed under Colorectal Neoplasms; 1,667 are open to participants now.
This study's planned enrollment of 50 is below the median of 76 across 4,800 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →Ain Shams University is the lead sponsor of 1,950 studies on the registry; 429 are open to participants now.
Of its 35 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALA Group: patients will receive Alpha lipoic acid 600mg oral tablet twice daily for 6 months
Drug: alpha lipoic acid 600 mg twice daily
Control group will receive identical placebo oral tablet twice daily for 6 months
Other: Placebo Tablet
Thiotex Forte® 600 mg film coated tablets.
Placebo tablets /twice daily for 6 months
Serum levels of malondialdehyde (MDA)
serum level of MDA (oxidative stress biomarker) will be assessed at baseline, after 3 months and after 6 months
Time frame: 6 months
Incidence of 5FU-induced oral mucositis
the number of patients who will develop oral mucositis will be recorded
Time frame: 6 months
Time to develop grade 2 or more Oral Mucositis
Time in days from the start of chemotherapy till the first appearance of grade 2 or more mucositis will be recorded for each patient
Time frame: 6 months
Duration of grade 3 or 4 Oral Mucositis
the time in days from the start of chemotherapy till the patient will develop grade 3 or 4 oral mucositis
Time frame: 6 months
Number of participants with dose delay/ reduction in chemotherapy due to Oral Mucositis development.
Time frame: 6 months
Assessment of pain score.
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 )
Time frame: 6 months
Assessment of serum levels of Interleukin 1β (IL-1β).
serum level of Interleukin 1β (IL-1β) will be measured at baseline and after 3 months then after 6 months
Time frame: 6 months
Patient's quality of life using Patient-Reported Oral Mucositis Symptom (PROMS) scale
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.
Time frame: 6 months
the safety of ALA
the incidence of adverse effects that will occur during the study will be recorded
Time frame: 6 months
Plan to share: No
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Thioctic Acid