B-Receptor Signaling in Cardiomyopathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daniel Bernstein, Stanford University
ClinicalTrials.gov Identifier:
NCT01135849
First received: June 1, 2010
Last updated: October 31, 2011
Last verified: October 2011
  Purpose

We hope to determine the importance of different genes (including B receptors) in anthracycline-induced cardiomyopathy. This has important benefits to patients exposed to anthracyclines, as this could help determine whether certain individuals have increased susceptibility to cardiac injury.


Condition
Carcinomas
Amyloidosis
Anal Cancer
Anemia
Cholangiocarcinoma of the Extrahepatic Bile Duct
Transitional Cell Carcinoma of Bladder
Bone Marrow Transplant Failure
Bone Cancer
Cancer of Brain and Nervous System
Breast Cancer
Carcinoma of the Large Intestine
Endocrine Cancer
Esophageal Cancer
Eye Cancer
Gall Bladder Cancer
Gastric (Stomach) Cancer
Gastrooesophageal Cancer
Gastrointestinal Stromal Tumor (GIST)
Gynecologic Cancers
Head and Neck Cancers
Hepatobiliary Neoplasm
Kidney (Renal Cell) Cancer
Leukemia
Lung Cancer
Hodgkin Disease
Lymphoma, Non-Hodgkin
Mesothelioma
Multiple Myeloma
Myelodysplastic Syndromes (MDS)
Neuroendocrine Tumors
Myeloproliferative Disorders
Pancreatic Cancer
Prostate Cancer
Skin Cancer
Soft Tissue Sarcoma
Testicular Cancer
Thymus Cancer
Thyroid Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: B-Receptor Signaling in Cardiomyopathy

Resource links provided by NLM:


Further study details as provided by Stanford University:

Biospecimen Retention:   Samples Without DNA

cheek swab or blood drawn for DNA extraction


Enrollment: 99
Study Start Date: November 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Detailed Description:

There is a strong correlation between total doxorubicin dose and anti-tumor efficacy, however, the clinical utility of doxorubicin is severely limited by its cardiotoxicity. With improved methods of detecting subtle changes in cardiac function, e.g. alterations in left ventricular wall stress (1), the incidence of doxorubicin cardiotoxicity is now appreciated to be much higher than previously suspected, documented in 65% of long-term survivors of childhood cancer, even at doses as low as 228 mg/m2. This cardiotoxicity is dose-related, and higher doses are related to a higher incidence of clinical heart failure (2). Doxorubicin's cardiotoxicity is thought to be mediated through the generation of free radicals and through mitochondrial and membrane damage.

We wish to determine whether beta-receptor genotype affects anthracycline-induced cardiomyopathy. We will correlate beta-receptor genotype with difference in wall stress post-anthracycline exposure, and with difference in shortening fraction. We plan to recruit 300 patients over a two-year period. Inclusion criteria includes past exposure to anthracycline for cancer treatment and an echocardiogram 6 - 48 months after exposure to anthracyclines.

The mean difference in 1.) wall stress and 2.) shortening fraction between each minor allele subgroup and wild type subgroup, for both beta-1 and beta-2 will be assessed using unpaired t-test analyses . We will assess through multivariate linear regression whether there are interactions between differences in wall stress or fractional shortening and other variables such as age, gender, dose of anthracycline, type of anthracycline given, and time between anthracycline exposure and echocardiogram. Those who receive other cardiotoxic drugs (such as trastuzumab for breast cancer) will be analyzed separately.

  Eligibility

Ages Eligible for Study:   up to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients exposed to anthracycline who have had an echocardiogram at least six months of initial exposure.

Criteria

Inclusion Criteria:1.) Past exposure to anthracycline chemotherapy for cancer

2.) Echocardiogram at least six months after exposure to anthracyclines (in patients over the age of 40, the echocardiogram must be obtained within 6 - 48 months of anthracycline exposure)

3.) Ability to understand and the willingness to sign a written informed consent document.

We have no age, gender, or ethnic background limitations. Due to the increased frequency of cardiovascular disease from other causes in adults over 40 years, we will limit enrollment to those patients with an echocardiogram 6 - 48 months after the completion of anthracycline exposure. Children will be included and will be eligible if they have an echocardiogram at least 6 months after completion of anthracycline treatment..

Exclusion Criteria:1.) Congenital heart disease (other than patent foramen ovale)

2.) Pre-existing cardiomyopathy before anthracycline administration

3.) Patients with Down syndrome

4.) Patients receiving B-blocker therapy at the time of anthracycline exposure

5.) Pregnant patients (if their echocardiogram was obtained either during pregnancy or within three months of pregnancy)

All participants will be cancer survivors. To minimize bias from post-partum cardiomyopathy, pregnant patients will be excluded if their echocardiogram was obtained during pregnancy or within three months of pregnancy. HIV-positive persons will not be excluded from the study.

Of note, some patients receive a MUGA (multigated acquisition) study to evaluate left ventricular ejection fraction. Patients who receive only a MUGA scan will NOT be included in the study - an echocardiogram is necessary

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01135849

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Daniel Bernstein
Investigators
Principal Investigator: Daniel Bernstein Stanford University
  More Information

No publications provided

Responsible Party: Daniel Bernstein, Professor, Stanford University
ClinicalTrials.gov Identifier: NCT01135849     History of Changes
Other Study ID Numbers: PEDSVAR0038, SU-11172008-1345
Study First Received: June 1, 2010
Last Updated: October 31, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Prostatic Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Pancreatic Neoplasms
Head and Neck Neoplasms
Esophageal Neoplasms
Urinary Bladder Neoplasms
Sarcoma
Cardiomyopathies
Thyroid Neoplasms
Breast Neoplasms
Carcinoma
Neoplasms
Mesothelioma
Neoplasms, Mesothelial
Lymphoma, Non-Hodgkin
Myeloproliferative Disorders
Carcinoma, Transitional Cell
Neuroendocrine Tumors
Hodgkin Disease
Amyloidosis
Cholangiocarcinoma
Gastrointestinal Stromal Tumors
Testicular Neoplasms
Brain Neoplasms
Carcinoma, Renal Cell
Colorectal Neoplasms
Genital Neoplasms, Male

ClinicalTrials.gov processed this record on October 01, 2014