B-Receptor Signaling in Cardiomyopathy | Clinical Trial

Key information

Conditions

Carcinomas Adenocarcinoma Adenoma Amyloidosis Anal Cancer Anemia Anus Diseases Anus Neoplasms Biliary Tract Diseases Biliary Tract Neoplasms Blood Protein Disorders Bone Cancer Bone Diseases Bone Marrow Diseases Bone Marrow Transplant Failure Bone Neoplasms Brain Diseases Brain Neoplasms Breast Cancer Breast Diseases Breast Neoplasms Cancer of Brain and Nervous System Carcinoma Carcinoma of the Large Intestine Carcinoma, Renal Cell Cardiovascular Diseases Central Nervous System Diseases Central Nervous System Neoplasms Cholangiocarcinoma of the Extrahepatic Bile Duct Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Cancer Endocrine Gland Neoplasms Endocrine System Diseases Esophageal Cancer Esophageal Diseases Esophageal Neoplasms Eye Cancer Eye Diseases Eye Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gall Bladder Cancer Gallbladder Diseases Gallbladder Neoplasms Gastric (Stomach) Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms Gastrointestinal Stromal Tumor (GIST) Gastrointestinal Stromal Tumors Gastrooesophageal Cancer Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Gonadal Disorders Gynecologic Cancers Head and Neck Cancers Head and Neck Neoplasms Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hepatobiliary Neoplasm Hodgkin Disease Immune System Diseases Immunoproliferative Disorders Intestinal Diseases Intestinal Neoplasms Kidney (Renal Cell) Cancer Kidney Diseases Kidney Neoplasms Leukemia Lung Cancer Lung Diseases Lung Neoplasms Lymphatic Diseases Lymphoma Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Male Urogenital Diseases Mesothelioma Metabolic Diseases Multiple Myeloma Musculoskeletal Diseases Myelodysplastic Syndromes Myelodysplastic Syndromes (MDS) Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Neoplasms, Nerve Tissue Neoplasms, Plasma Cell Nervous System Diseases Nervous System Neoplasms Neuroectodermal Tumors Neuroendocrine Tumors Neurologic Manifestations Nutritional and Metabolic Diseases Pancreatic Cancer Pancreatic Diseases Pancreatic Neoplasms Paraproteinemias Pathological Conditions, Signs and Symptoms Prostate Cancer Prostatic Diseases Prostatic Neoplasms Proteostasis Deficiencies Rectal Diseases Rectal Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Sarcoma Signs and Symptoms Skin Cancer Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Soft Tissue Sarcoma Stomach Diseases Stomach Neoplasms Testicular Cancer Testicular Diseases Testicular Neoplasms Thoracic Neoplasms Thymus Cancer Thymus Neoplasms Thyroid Cancer Thyroid Diseases Thyroid Neoplasms Transitional Cell Carcinoma of Bladder Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Vascular Diseases

Age range

Up to 40 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Stanford University School of Medicine

Stanford, California, 94305, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

Development of cardiomyopathy

Time frame: Within 5 years after receiving anthracyclines.

Decrease in fractional shortening below normal (<28%)

Sponsors and collaborators

Lead sponsor

Daniel Bernstein

Other

Registry information

Important dates

Study start: 2008
Primary completion: 2010
Study completion: 2010
First posted: Jun 3, 2010
Registry last updated: Nov 17, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed