Prevention of Doxorubicin-induced Cardiotoxicity in Breast Cancer Patients

NCT06703593 | Completed Phase 2

• 1 other identifier: CL-2311
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

According to the European Society of Cardiology 2022, the primary prevention of cancer therapyrelated cardiovascular toxicity during anthracycline chemotherapy include renin-angiotensin- aldosterone system blockers, beta-blockers, and mineralocorticoid receptor antagonists that have shown a significant benefit in preventing left ventricular ejection fraction (LVEF) reduction, but with no statistical differences in the incidence on the various other clinical outcomes as overt congestive heart failure (CHF). Also, other strategies have been investigated including; adjusting the infusion time and dose intensity of anthracyclines. Dexrazoxane and liposomal anthracyclines are currently approved in patients with high and very high chemotherapy-related cardiovascular disease (CTRCD) risk or who have already received high cumulative anthracyclines doses (Lyon, 2022). The incidence is about 4% when the dose of doxorubicin is 500-550 mg/m2, 18% when the dose is 551-600 mg/m2 and 36% when the dose exceeds 600 mg/m2 (Lefrak, 1973). Alpha-lipoic acid (ALA) was reported to have a cardioprotective role against doxorubicin-induced cardiotoxicity through attenuation of oxidative stress via scavenging reactive oxygen species (ROS), regenerating endogenous antioxidants including glutathione, vitamin E, and C, its metal chelation activity and its ability to repair oxidative damage. (Werida et al, 2022)

Conditions

Breast Cancer Female

Keywords

Alpha lipoic acid, Anthracyclines induced Cardiotoxicity

Outcome Measures

Primary Outcomes (2)

• Changes in echocardiographic findings

  Elevation or maintenance of Ejection fraction percentage (EF %)

  Approximately few days ( less than a week ) before Cycle 1 "baseline" and after Cycle 4 "End Cycle" of Doxorubicin. Each cycle is 21 days.

• Changes in serum levels of pro brain natriuretic peptide (pro-BNP) and cardiac troponins

  Decline in serum concentration of pro brain natriuretic peptide (pro-BNP) measured in picograms per milliliter (pg/mL) and cardiac troponins measured in picograms per milliliter (pg/mL).

  Just before Cycle 1 "baseline" and 1 hour after Cycle 4 "End Cycle" of Doxorubicin. Each cycle is 21 days.

Secondary Outcomes (1)

• Changes in the oxidative stress marker malondialdehyde (MDA)

  ust before Cycle 1 "baseline" and 1 hour after Cycle 4 "End Cycle" of Doxorubicin. Each cycle is 21 days.

Study Arms (2)

Alpha Lipoic acid intervention arm

EXPERIMENTAL

Alpha Lipoic acid 1200 mg daily for 6 months

Drug: Alpha lipoic acid

No intervention arm

NO INTERVENTION

not taking Alpha Lipoic acid

Interventions

Alpha lipoic acid DRUG

ALA effectively inhibits nuclear factor-kappa B with subsequent decreasing proinflammatory cytokines production (TNF-α, IL-6) and increasing the release of anti- inflammatory cytokines such as interleukin-10 (Haghighatdoost and Hariri, 2019). Relying on the antioxidant and anti-inflammatory effect of Alpha lipoic acid confirmed by a variety of studies in vitro and in vivo, ALA is selected to be studied in Egyptian breast cancer patients who will be treated with doxorubicin including regimens.

Also known as: Neuropatex, lipoic acid

Alpha Lipoic acid intervention arm

Eligibility Criteria

• Age: 19 Years+
• Gender Eligibility Details: 1. Women aged more than 18 years 2. Breast cancer diagnosis 3. Entering first cycle of chemotherapy containing ATC 4. Subject must be willing and able to sign an informed consent
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged more than 18 years
• Breast cancer diagnosis
• Entering first cycle of chemotherapy containing ATC
• Subject must be willing and able to sign an informed consent

You may not qualify if:

• History of renal (serum creatinine greater than 2.0 mg/ml) or hepatic insufficiency (bilirubin\> 3.0 mg/dl or serum albumin \< 3.5 g/dl or prothrombin time \< 60% in the absence of orally administered anticoagulant therapy or ultrasound signs of chronic liver damage
• History of heart failure
• Baseline LVEF \< 50% determined by transthoracic echocardiogram
• Current participation in any other clinical investigation
• History of severe adverse reaction to Alpha lipoic acid
• Concomitant use of Trastuzumab (HER2 positive patients)
• Previous intake of alpha lipoic acid in the previous 3 months
• Women with prior exposure to anthracyclines and neurotoxic agents (Cis-platin, vincristine, paclitaxel, docetaxel, foscarnet, isonicotinic acid hydrazide "INH,", etc.) in the last 6 months.
• Presence of clinical evidence for severe cardiac illness (i.e., angina pectoris and arrhythmias)
• Any condition that contraindicates chemotherapy (i.e., pregnancy, lactation)

Sponsors & Collaborators

• British University In Egypt: lead
• Ain Shams University: collaborator

Study Sites (1)

The British University in Egypt

Cairo, El-Sherouk City, 11837, Egypt

Location

MeSH Terms

Interventions

Thioctic Acid

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Demonstrator and Teaching assistant at the Clinical Pharmacy Practice Department

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: November 25, 2024
• Study Start: October 1, 2023
• Primary Completion: April 1, 2025
• Study Completion: May 1, 2025
• Last Updated: October 1, 2025

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)