Anticancer Treatment of Breast Cancer Related to Cardiotoxicity and Dysfunctional Endothelium

NCT02652975 | Completed

• 1 other identifier: ABCDE_AUH
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

Several cytotoxic regimens are related to endothelial cell damage and vascular toxicity. Endothelial dysfunction is implicated in the pathogenesis of all known cardiovascular diseases (CVD) and closely related to the metabolic syndrome. Both CVD and diabetes contributes importantly to total mortality and to breast cancer (BC) specific mortality. In the epidemiological part of the project, the investigators will determine the prevalence and incidence of cardiovascular and metabolic morbidity/mortality in early BC patients compared to the Danish background population. In the clinical part, the investigators will study the changes of endothelial function and metabolic parameters in BC patients receiving chemotherapy. With increasing number of BC survivors, long-term consequences of curative cancer treatment should be studied. The investigators hypothesize that cytotoxic therapy worsens metabolic parameters possibly through endothelial dysfunction. If this is true, the next step will be to evaluate how strict metabolic control will affect prognosis.

Conditions

Breast Neoplasms; Endothelial Dysfunction; Cardiovascular Disease; Metabolic Syndrome

Outcome Measures

Primary Outcomes (6)

• Changes in endothelial dysfunction evaluated using plethysmography.

  Measured before start of chemotherapy (week 0), immediately after ended chemotherapy (week 18) and one year after ended chemotherapy (week 70).

• Changes in aortic pressure evaluated using applanation tonometry (SphygmoCor)

  Measured before start of chemotherapy (week 0), immediately after ended chemotherapy (week 18) and one year after ended chemotherapy (week 70).

• Changes in blood pressure evaluated by 24 hour blood pressure measurements.

  Measured before start of chemotherapy (week 0), immediately after ended chemotherapy (week 18) and one year after ended chemotherapy (week 70).

• Changes in metabolic measurements using the blood samples listed in descriptive field.

  P-Kolesterol, P-Kolesterol HDL, P-Kolesterol LDL, P-Triglyceride, P-Glukose, P-Progesteron, P-Testosteron, P-Von Willebrand-faktor, P-Natrium, P-Kalium, P-Kreatinin and P-Østradiol.

  Measured before start of chemotherapy (week 0), immediately after ended chemotherapy (week 18) and one year after ended chemotherapy (week 70).

• Changes in body composition using DEXA scans

  Measured before start of chemotherapy (week 0), immediately after ended chemotherapy (week 18) and one year after ended chemotherapy (week 70).

• Changes in risk of cardiovascular death within 10 years using the SCORE-system.

  The SCORE-system is a well- established and validated method using age, gender, smoking status, systolic blood pressure and plasma cholesterol for risk stratification.

  Measured before start of chemotherapy (week 0), immediately after ended chemotherapy (week 18) and one year after ended chemotherapy (week 70).

Study Arms (3)

Category 1

EXPERIMENTAL

Examination of participants prior to chemotherapy. Venous occlusion plethysmography SphygmoCor 24hour blood pressure DEXA scan Laboratory blood samples

Procedure: Venous occlusion plethysmography; Procedure: SphygmoCor; Procedure: 24hour blood pressure; Procedure: DEXA scan; Biological: Laboratory blood samples

Category 2

EXPERIMENTAL

Examination of participants immediately after chemotherapy. Venous occlusion plethysmography SphygmoCor 24hour blood pressure DEXA scan Laboratory blood samples

Procedure: Venous occlusion plethysmography; Procedure: SphygmoCor; Procedure: 24hour blood pressure; Procedure: DEXA scan; Biological: Laboratory blood samples

Category 3

EXPERIMENTAL

Examination of participants one year after chemotherapy. Venous occlusion plethysmography SphygmoCor 24hour blood pressure DEXA scan Laboratory blood samples

Procedure: Venous occlusion plethysmography; Procedure: SphygmoCor; Procedure: 24hour blood pressure; Procedure: DEXA scan; Biological: Laboratory blood samples

Interventions

Venous occlusion plethysmography PROCEDURE

To characterize endothelial function in vivo the effect of vasodilatating substances is measured in the forearm circuit. The substances is administered via a thin catheter placed in the Brachial artery near the elbow in local anesthesia. Once the vessels dilate, the blood flow in the forearm will increase and the flow change is a measure of the vasodilatory capacity of that substance. The change is measured with classical venous occlusion plethysmography. The method described is established at Aarhus University Hospital and has been used for several decades to illustrate the effect of vasoactive drugs on the human circulation, meaning it is a proven and well documented method.

Category 1; Category 2; Category 3

SphygmoCor PROCEDURE

Applanation tonometry (pulse wave velocity and central blood pressure/arterial stiffness): The central blood pressure and the augmentation index is estimated from the shape of the radial pulse wave measured with a tonometer. Pulse wave velocity (PWV) is calculated from the average difference between the pulse pressure wave measured with a tonometer and the R in an ECG recorded simultaneously.

Category 1; Category 2; Category 3

24hour blood pressure PROCEDURE

24 hour blood pressure measurement

Category 1; Category 2; Category 3

DEXA scan PROCEDURE

Measurements of body composition: Total body fat and fat free mass is measured by Dual Energy X-ray Absorptiometry (DEXA).

Category 1; Category 2; Category 3

Laboratory blood samples BIOLOGICAL

Fasting blood tests are drawn from an antecubital placed catheter (albumin, ALAT/ASAT, alkaline phosphatase, bilirubin, gammaglutamyl transferase, coagulation factors, red and white blood cells, creatinin, potassium, sodium, fasting lipids, fasting glucose, hemoglobin A1C, insulin, sex hormones, von Willebrand factor, low grade inflammation markers, DNA and RNA for later analyses, including relevant coding genes). Further more urine samples to determine possible systemic impact of cardiovascular disease. We will create a biobank containing urine and blood samples from participants for future research, provided that the participant gives her permission. Responsibility for the biobank lies with the project responsible physician, Anders Bonde Jensen.

Category 1; Category 2; Category 3

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• women referred to receive adjuvant chemotherapy for primary operable non-metastatic breast cancer

You may not qualify if:

• former og actual use of cytostatics
• pregnancy

Sponsors & Collaborators

• University of Aarhus: lead
• Danish Cancer Society: collaborator

Study Sites (1)

Aarhus University Hospital

Aarhus, Jutland, 8000, Denmark

Location

Related Publications (1)

• Fredslund SO, Gravholt CH, Laursen BE, Jensen AB. Key metabolic parameters change significantly in early breast cancer survivors: an explorative PILOT study. J Transl Med. 2019 Apr 1;17(1):105. doi: 10.1186/s12967-019-1850-2.

  PMID: 30935397 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Cardiovascular Diseases; Metabolic Syndrome

Interventions

Blood Pressure; Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Radiography; Diagnostic Imaging; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Anders B. Jensen, Professor

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2015
• First Posted: January 12, 2016
• Study Start: September 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: October 9, 2019

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)