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

This study has been completed.
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Ottawa Heart Institute Research Corporation
ClinicalTrials.gov Identifier:
NCT00247975
First received: October 31, 2005
Last updated: February 6, 2012
Last verified: February 2012

October 31, 2005
February 6, 2012
March 2006
October 2010   (final data collection date for primary outcome measure)
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 ]
1) Change in EF (measure by RNA) at one year, compared to the patient’s own baseline.
Complete list of historical versions of study NCT00247975 on ClinicalTrials.gov Archive Site
  • 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 ]
  • A) Effect of L-carnitine versus placebo on:
  • 1) LV end-systolic and end-diastolic volumes (RNA)
  • 2) LV diastolic dysfunction (ECHO)
  • 3) serum TnT and BNP measured with each cycle of chemotherapy (immediately prior to and 3 days after chemotherapy)
  • 4) composite outcome of: cardiac death, clinical congestive heart failure, reduction in EF requiring termination of anthracycline therapy (LVEF reduction ≥ 10% and LVEF < 50%), dexrazoxane use or “anthracycline-induced cardiotoxicity”.
  • 5) adverse events (e.g. chemotherapy efficacy, seizures, nausea, diarrhea).
  • B)
  • 6) correlation of serum biomarkers (serum L-Carnitine levels, serum TnT, BNP) with surrogate markers of cardiotoxicity (LV ejection fraction, LV volumes and diastolic dysfunction) will be performed.
Not Provided
Not Provided
 
Ability of L-carnitine to Prevent Heart Damage in Breast Cancer Patients Receiving Anthracycline Chemotherapy
Primary Prevention of Anthracycline-Induced Cardiotoxicity With L-Carnitine in Patients With Breast Cancer (PPACC)-Pilot Study

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.

Not Provided
Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Heart Failure
Drug: L-carnitine
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.
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
144
October 2011
October 2010   (final data collection date for primary outcome measure)

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.
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00247975
CIHR #: 126541
Yes
Ottawa Heart Institute Research Corporation
Ottawa Heart Institute Research Corporation
Canadian Institutes of Health Research (CIHR)
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
Ottawa Heart Institute Research Corporation
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP