Alpha-Lipoic Acid in Breast Cancer Patients

Study Overview
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Brief Summary
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• Investigate the ability of alpha lipoic acid to counter act anthracycline associated cardiotoxicity and cumulative taxens-related PN in patients with breast cancer.

Detailed Description
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Fifty breast cancer patients with stage from stage I to stage III will be involved in this study. Staging is done according to the American joint committee on cancer: TNM staging of breast cancer. All participants will be recruited from Tanta Oncology Center. The study will be approved by Research Ethics Committee of Damanhour University. All participants will give their consent. All 64 patients will be scheduled to receive 4 cycles of AC: cycled every 21 days followed by weekly cycle of taxol for 12 weeks. Patients will be classified as follow: Group one: 32 patients will receive four cycles of AC followed by weekly taxol for 12 weeks plus placebo. Group two: 32 patients will receive the same regimen as group 1 in addition to oral 600 mg alpha lipoic acid (ALA) once daily. All patients will be submitted to: Full patient history and clinical examination. Venous blood will be collected before the first cycle of chemotherapy and after the last cycle of chemotherapy. 1- Cardio-toxcity assessment: i. Echo-cardiogram. ii. Troponin I. iii. The Brain Natriuretic Peptide (BNP). 2- Neurotoxicity assessment: i. National Cancer Institute common Terminology criteria for Adverse Effect grading: NCI-CTCAE version 4.0. ii. Neurotoxicity questionnaire from the validated Functional Assessment of cancer therapy/gynecologic oncology group taxane specific neurotoxicity questionnaire: FACT-Taxane. iii. Neurotensin 3- Oxidative stress and inflammatory markers: i. Malondialdehyde (MDA). ii. TNF-alpha

Official Title
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Role of Alpha-Lipoic Acid Against Chemotherapy Induced Toxicities in Breast Cancer Patients

Conditions
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Breast Cancer, Chemotherapeutic Toxicity

Intervention / Treatment
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* Dietary Supplement: Alpha-lipoic acid Plus Chemotherapy (doxorubicin (also known as Adriamycin) plus cyclophosphamide followed by taxol)
* Other: Placebo Plus Chemotherapy (doxorubicin (also known as Adriamycin) plus cyclophosphamide followed by taxol)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients age ≥ 18 and < 70 years old with confirmed stage from stage I to stage III. No evidence of metastases at initial assessment. Patients has to have a good performance status (ECOG 0-2) according to Eastern Cooperative Oncology Group (ECOG) score. Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin level ≥ 10g/dL). Patients with adequate liver function (serum creatinine < 1.5 mg/dL) and adequate renal function (serum creatinine < 1.5 mg/dL, creatinine clearance (CrCl) > 45 ml/min). Either pre operative or post operative chemotherapy are allowed. Exclusion Criteria: Evidence of metastases at initial assessment. Pregnancy or breast-feeding patients. Prior exposure to neurotoxic chemotherapy was not allowed (no carboplatin, vincristine, vinblastine, paclitaxel, or docetaxol ) for 6 months prior study treatment. Clinical evidence of serious cardiac illness (myocardial dysfunctional, angina pectoris requiring anti-angina medication, poorly controlled hypertension, and uncontrolled arrhythmias). Patients with a reduced cardiac output with a left ventricular ejection fraction (LVEF) ejection fraction < 50%. Patients who had evidence of pre-existing peripheral neuropathy resulting from another reason (diabetes). Patients with a history of allergy to alpha-lipoic acid. Concomitant use of multivitamins (vitamin E), opioids, anticonvulsants, tricyclic antidepressants, other neuropathic pain medication modifying agents (e.g., gabapentin, lamotrigine, carbamazepine, phenytoin, or tricyclic antidepressants) are not allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind study, Patients will be classified as follow: Group one: 32 patients will receive four cycles of AC followed by weekly taxol for 12 weeks plus placebo. Group two: 32 patients will receive four cycles of AC followed by weekly taxol for 12 weeks plus oral 600 mg alpha lipoic acid (ALA) once daily.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy plus Placebo for six Months<br>• Group one: 32 patients will receive four cycles of AC followed by weekly taxol for 12 weeks plus Placebo. | Other: Placebo Plus Chemotherapy (doxorubicin (also known as Adriamycin) plus cyclophosphamide followed by taxol)<br>* Placebo with four cycles of doxorubicin (also known as Adriamycin) plus cyclophosphamide followed by weekly taxol for 12 weeks.<br>* Other names: placebo;|
| Experimental: Chemotherapy plus alpha lipoic acid for six Months<br>• Group two: 32 patients will receive four cycles of AC followed by weekly taxol for 12 weeks in addition to oral 600 mg alpha lipoic acid (ALA) once daily. | Dietary Supplement: Alpha-lipoic acid Plus Chemotherapy (doxorubicin (also known as Adriamycin) plus cyclophosphamide followed by taxol)<br>* 600 mg Alpha-lipoic acid daily (an antioxidant that's in many foods, and it's made naturally in the investigator's bodies) with four cycles of doxorubicin (also known as Adriamycin) plus cyclophosphamide followed by weekly taxol for 12 weeks..<br>* Other names: Thiotacid 600 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiotoxcity assessment | serum Brain Natriuretic Peptide (BNP) level | six months | 
| Neurotoxicity assessment | Neurotensin level | six months | 
| oxidative stress and inflammatory markers | TNF-alpha level | six months | 
| MDA | Malondialdehyde | six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alpha-lipoic acid, taxol, Adriamycin, cyclophosphamide, breast cancer, Brain Natriuretic Peptide (BNP)., Neurotensin, TNF-alpha