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

Sponsor:	University of Ottawa Heart Institute
Collaborator:	Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):	University of Ottawa Heart Institute
ClinicalTrials.gov Identifier:	NCT00247975

Purpose

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	Intervention	Phase
Heart Failure	Drug: L-carnitine	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Heart Failure

Drug Information available for: Carnitine

U.S. FDA Resources

Further study details as provided by University of Ottawa Heart Institute:

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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]

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) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
"Anthracycline-induced cardiotoxicity" and clinical cardiac outcomes [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Serum L-carnitine levels [ Time Frame: 4 months ] [ Designated as safety issue: No ]
To assess: the safety of L-carnitine [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
the effect of anthracyclines on plasma L-carnitine levels [ Time Frame: 4 months ] [ Designated as safety issue: No ]
the correlation of L-carnitine levels with serum TnT and BNP levels [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	144
Study Start Date:	March 2006
Study Completion Date:	October 2011
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Intervention Details:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00247975

Locations

Canada, Ontario
University of Ottawa Heart Institute
Ottawa, Ontario, Canada, K1Y 4W7

Sponsors and Collaborators

University of Ottawa Heart Institute

Canadian Institutes of Health Research (CIHR)

Investigators

Principal Investigator:	Benjamin JW Chow, MD, FRCPC	University of Ottawa Heart Institute
Study Chair:	Rob S Beanlands, MD, FRCPC	University of Ottawa Heart Institute
Study Chair:	Haissam Haddad, MD, FRCPC	University of Ottawa Heart Institute
Study Chair:	George Wells, M.Sc., PhD	University of Ottawa Heart Institute
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

More Information

No publications provided

Responsible Party:	University of Ottawa Heart Institute
ClinicalTrials.gov Identifier:	NCT00247975 History of Changes
Other Study ID Numbers:	CIHR #: 126541
Study First Received:	October 31, 2005
Last Updated:	February 6, 2012
Health Authority:	Canada: Health Canada

Keywords provided by University of Ottawa Heart Institute:

L-carnitine
Breast cancer
Anthracycline Cardiotoxicity
Primary prevention

Anthracycline induced cardiotoxicity
Breast Cancer
Left Ventricular Ejection Fraction

Additional relevant MeSH terms:

Breast Neoplasms
Heart Failure
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Heart Diseases
Cardiovascular Diseases

Carnitine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012