Ability of L-carnitine to Prevent Heart Damage in Breast Cancer Patients Receiving Anthracycline Chemotherapy

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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

L-carnitine

About this trial

This is an interventional prevention trial for Heart Failure focused on measuring L-carnitine, Breast cancer, Anthracycline Cardiotoxicity, Primary prevention, Anthracycline induced cardiotoxicity, Left Ventricular Ejection Fraction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Female patients must have histologically or cytologically indicated breast cancer (stages I, II, III) eligible for adjuvant anthracycline chemotherapy [FEC100 or AC-Taxol(paclitaxel) every 21 days. HER2 negative or HER2 positive breast cancer by immunohistochemistry (IHC3+) and/or fluorescent in-situ hybridization. Eastern cooperative oncology group (ECOG) performance status = 0, 1, 2 Age ≥ 18 years old. Ability to understand and the willingness to sign a written informed consent document. The effects of L-carnitine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Exclusion Criteria: Patients with evidence of metastatic breast cancer. Resting LV ejection fraction < 50%. Patients having received previous anthracycline therapy or contraindication to anthracycline. Patients having a contraindication to L-carnitine therapy Dexrazoxane therapy at the time of enrollment. Patients with abnormal baseline bloodwork: hemoglobin ≤ 100 mg/L platelets ≤ 100 x 10^9/L white blood cells ≤ 4 x 10^9/L creatinine, AST, ALT, bilirubin > 1.5 x the upper normal limits Participation in another randomized clinical trial. Patients having significant cardiac disease (previous myocardial infarction, congestive heart failure, or hemodynamically significant valvular heart disease) that would limit compliance with study requirements. Patients taking medication that may affect LV function (b-blockers, amiodarone, ACE-inhibitors, calcium channel blockers, or digoxin). Patients with symptoms of heart failure. Patients unable to participate in a study requiring long term follow up. Pregnant or lactating women.

Sites / Locations

University of Ottawa Heart Institute

Outcomes

Primary Outcome Measures

To compare the effects of L-carnitine therapy versus placebo on left ventricular (LV) ejection fraction (EF) as a marker of anthracycline induced cardiotoxicity

Secondary Outcome Measures

To compare the effects of L-carnitine therapy versus placebo on: other potential markers of anthracycline induced cardiotoxicity such as LV volume, LV systolic and diastolic function, troponin T (TnT) and NT-pro-brain natriuretic peptide (BNP)

"Anthracycline-induced cardiotoxicity" and clinical cardiac outcomes

Serum L-carnitine levels

To assess: the safety of L-carnitine

the predictive value of serum biomarkers (TnT, BNP, and L-carnitine levels) for cardiotoxicity and cardiac outcome (ejection fraction, LV volumes, congestive heart failure, and cardiac death)

the effect of anthracyclines on plasma L-carnitine levels

the correlation of L-carnitine levels with serum TnT and BNP levels

Full Information

NCT ID

NCT00247975

First Posted

October 31, 2005

Last Updated

August 12, 2022

Sponsor

Ottawa Heart Institute Research Corporation

Collaborators

Canadian Institutes of Health Research (CIHR)

1. Study Identification

Unique Protocol Identification Number

NCT00247975

Brief Title

Ability of L-carnitine to Prevent Heart Damage in Breast Cancer Patients Receiving Anthracycline Chemotherapy

Official Title

Primary Prevention of Anthracycline-Induced Cardiotoxicity With L-Carnitine in Patients With Breast Cancer (PPACC)-Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Terminated

Why Stopped

Insufficient recruitment

Study Start Date

March 2006 (undefined)

Primary Completion Date

October 2010 (Actual)

Study Completion Date

October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ottawa Heart Institute Research Corporation

Collaborators

Canadian Institutes of Health Research (CIHR)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Breast cancer is very common and afflicts 1 in 9 North American women. The treatment of breast cancer often requires the use of chemotherapy including "anthracyclines". Anthracyclines can damage the heart resulting in heart failure and even death. Clinicians and researchers are continually seeking methods that will reduce the toxic effects of anthracycline treatment. L-carnitine is a substance that is produced naturally in the body and is required for normal heart function. Animal studies have suggested that L-carnitine protects the heart from the effects of anthracyclines, however this has not been verified in humans. This study will assess the potential role of L-carnitine in the prevention of anthracycline induced heart damage. The investigators will enroll 144 patients into this study. Patients will be randomly assigned to L-carnitine therapy or to standard care (no L-carnitine therapy). Patients in the L-carnitine group will receive oral and intravenous L-carnitine prior to and after their anthracycline therapy. Patients will undergo regular follow up and testing to assess heart function. The investigators believe that patients treated with L-carnitine will benefit and have fewer complications associated with anthracycline treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure

Keywords

L-carnitine, Breast cancer, Anthracycline Cardiotoxicity, Primary prevention, Anthracycline induced cardiotoxicity, Left Ventricular Ejection Fraction

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

L-carnitine

Other Intervention Name(s)

Sigma-Tau

Intervention Description

Patients will be randomized to L-carnitine therapy or placebo. Patients in the treatment group will receive oral L-carnitine (3 grams daily) for 3 days prior to chemotherapy, 1 gram of intravenous L-carnitine (5 cc over 5 minutes, prior to chemotherapy) on the day of chemotherapy and oral L-carnitine (3 grams daily) for 3 days after chemotherapy.

Primary Outcome Measure Information:

Title

To compare the effects of L-carnitine therapy versus placebo on left ventricular (LV) ejection fraction (EF) as a marker of anthracycline induced cardiotoxicity

Time Frame

1 year

Secondary Outcome Measure Information:

Title

To compare the effects of L-carnitine therapy versus placebo on: other potential markers of anthracycline induced cardiotoxicity such as LV volume, LV systolic and diastolic function, troponin T (TnT) and NT-pro-brain natriuretic peptide (BNP)

Time Frame

1 year

Title

"Anthracycline-induced cardiotoxicity" and clinical cardiac outcomes

Time Frame

1 year

Title

Serum L-carnitine levels

Time Frame

4 months

Title

To assess: the safety of L-carnitine

Time Frame

1 year

Title

the predictive value of serum biomarkers (TnT, BNP, and L-carnitine levels) for cardiotoxicity and cardiac outcome (ejection fraction, LV volumes, congestive heart failure, and cardiac death)

Time Frame

1 year

Title

the effect of anthracyclines on plasma L-carnitine levels

Time Frame

4 months

Title

the correlation of L-carnitine levels with serum TnT and BNP levels

Time Frame

4 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Female patients must have histologically or cytologically indicated breast cancer (stages I, II, III) eligible for adjuvant anthracycline chemotherapy [FEC100 or AC-Taxol(paclitaxel) every 21 days. HER2 negative or HER2 positive breast cancer by immunohistochemistry (IHC3+) and/or fluorescent in-situ hybridization. Eastern cooperative oncology group (ECOG) performance status = 0, 1, 2 Age ≥ 18 years old. Ability to understand and the willingness to sign a written informed consent document. The effects of L-carnitine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Exclusion Criteria: Patients with evidence of metastatic breast cancer. Resting LV ejection fraction < 50%. Patients having received previous anthracycline therapy or contraindication to anthracycline. Patients having a contraindication to L-carnitine therapy Dexrazoxane therapy at the time of enrollment. Patients with abnormal baseline bloodwork: hemoglobin ≤ 100 mg/L platelets ≤ 100 x 10^9/L white blood cells ≤ 4 x 10^9/L creatinine, AST, ALT, bilirubin > 1.5 x the upper normal limits Participation in another randomized clinical trial. Patients having significant cardiac disease (previous myocardial infarction, congestive heart failure, or hemodynamically significant valvular heart disease) that would limit compliance with study requirements. Patients taking medication that may affect LV function (b-blockers, amiodarone, ACE-inhibitors, calcium channel blockers, or digoxin). Patients with symptoms of heart failure. Patients unable to participate in a study requiring long term follow up. Pregnant or lactating women.

Overall Study Officials: