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

Sponsor

Ottawa Heart Institute Research Corporation (Other)

Overall Status

Terminated

CT.gov ID

NCT00247975

Collaborator

Canadian Institutes of Health Research (CIHR) (Other)

Enrollment

Location

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: L-carnitine	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Mar 1, 2006

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2011

Outcome Measures

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 [1 year]

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) [1 year]
"Anthracycline-induced cardiotoxicity" and clinical cardiac outcomes [1 year]
Serum L-carnitine levels [4 months]
To assess: the safety of L-carnitine [1 year]
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) [1 year]
the effect of anthracyclines on plasma L-carnitine levels [4 months]
the correlation of L-carnitine levels with serum TnT and BNP levels [4 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Ottawa Heart Institute	Ottawa	Ontario	Canada	K1Y 4W7

Sponsors and Collaborators

Ottawa Heart Institute Research Corporation
Canadian Institutes of Health Research (CIHR)

Investigators

Principal Investigator: Benjamin JW Chow, MD, FRCPC, Ottawa Heart Institute Research Corporation
Study Chair: Rob S Beanlands, MD, FRCPC, Ottawa Heart Institute Research Corporation
Study Chair: Haissam Haddad, MD, FRCPC, Ottawa Heart Institute Research Corporation
Study Chair: George Wells, M.Sc., PhD, Ottawa Heart Institute Research Corporation
Study Chair: Susan Dent, MD, FRCPC, Ottawa Regional Cancer Centre
Study Chair: Sean Hopkins, B.Sc, RPEBC, Ottawa Regional Cancer Centre
Study Chair: Michele A Turek, MD, FRCPC, Ottawa Hospital