Vascular Functions in Myeloma Patients During Anti-tumor Therapy

NCT03776331 | Unknown

• 1 other identifier: Vascular-Myelom
• Study Type: observational
• Target: 96
• Locations: 0 countries
• Sites: N/A

Brief Summary

Treatment options for multiple myeloma have increased significantly over the last years with the approval of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). These therapies have markedly improved overall survival for these patients to a median of 5-7 years. Due to the advanced age, the myeloma patient collective has a high prevalence of pre-existing cardiovascular comorbidities. In addition, the primary disease process contributes to cardiovascular complications. With the beginning of anti-tumor therapy, an increased incidence of cardiovascular complications in myeloma patients can be determined. This includes hypertension, left ventricular dysfunction, heart failure and both arterial and venous thromboembolic events. The detailed mechanism by which proteasome inhibitors and immunomodulatory agents lead to increased cardiovascular events is not established at this time. Endothelial dysfunction, as a possible mechanism of cardiovascular toxicity, is difficult to assess. Flow-mediated dilation (FMD) is an noninvasive method to measure endothelial function by assessing the change in the vasodilatative reserve of the brachial artery. Several independent recent investigations implicate that vascular (endothelial) dysfunction precedes hypertension and heart failure. This has been related to a reduced level of metabolites of the l-arginine-nitric oxide (NO) signaling pathway. Hypothesis:

1. 1.Anti-myeloma therapy exert vascular toxicity by limiting endothelial function. Endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD) decreases after myeloma therapy.
2. 2.Patients with multiple myeloma have a limited endothelial function compared to a healthy control group.

Conditions

Cardiooncology; Myeloma; Endothelial Dysfunction

Keywords

Myeloma; Flow mediated dilation; Endothelial Dysfunction; Proteasome inhibitors

Outcome Measures

Primary Outcomes (1)

• Change of endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD)

  between baseline and 1 month data

Secondary Outcomes (21)

• Change of endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD)

  between baseline and 6 month data

• Change of endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD)

  between 1 and 6 month data

• Change of endothelial function, assessed by the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD) between baseline data in myeloma patients and control group

  baseline data

• Change of left ventricular pump function (3D-EF)

  between baseline and 1 month data/baseline and 6 month data/1 and 6 month data

• Change of left ventricular pump function (global longitudinal strain)

  between baseline and 1 month data/baseline and 6 month data/1 and 6 month data

Study Arms (2)

Myeloma Patients

Diagnostic Test: Flow mediated dilation

Controll group

Diagnostic Test: Flow mediated dilation

Interventions

Flow mediated dilation DIAGNOSTIC_TEST

Measurement of the change in the vasodilatative reserve of the brachial artery

Controll group; Myeloma Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The cohorts will be selected of the population of patients of the university clinic of Essen

You may qualify if:

• Age ≥ 18 years
• written consent

You may not qualify if:

• Severe pulmonary, valvular, or congenital heart disease with clinical dyspnoea symptoms
• Life expectancy less than 6 months
• Unstable angina pectoris or indication for coronary revascularization
• Valvular disease (aortic valve and mitral regurgitation greater than moderate, and aortic valve or mitral valve stenosis greater than moderate)
• Atrial fibrillation or flutter
• Chronic renal insufficiency (Cockcroft-Gault GFR \<30 mL / min)
• Severe cirrhosis (Child-Pugh B and C)
• Current or future indication for therapy with organic nitrates
• Leading non-cardiac cause of clinical dyspnea symptoms, such as high-grade obesity or lung disease in need of glucocorticoid therapy or oxygen therapy
• Other cause of clinical dyspnea symptoms, such as high-grade obesity or lung disease with need for glucocorticoid therapy or oxygen therapy

Sponsors & Collaborators

• University Hospital, Essen: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood tissue

MeSH Terms

Conditions

Neoplasms, Plasma Cell

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Study Officials

• Matthias Totzeck

  Universitätsklinikum Essen AOeR

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthias Totzeck

CONTACT

004920172384805; matthias.totzeck@uk-essen.de

Lena Hinrichs

CONTACT

015144531284; lena.hinrichs@uk-essen.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 10, 2018
• First Posted: December 14, 2018
• Study Start: December 28, 2018
• Primary Completion: December 28, 2019
• Study Completion: March 28, 2020
• Last Updated: December 19, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR