AzTrials
AzTrials

CardiooncologyNCT03776331

Vascular Functions in Myeloma Patients During Anti-tumor Therapy

An observational study of Cardiooncology and Myeloma, run by University Hospital, Essen.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Cardiooncology, Myeloma, Endothelial Dysfunction
What is being tested?
Flow mediated dilation
How many people
96 participants
Where
No sites listed yet
Study dates
28 Dec 2018to 28 Mar 2020
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

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

Who may be able to join

  • Age ≥ 18 years
  • written consent

Who cannot join

  • 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)
Show all 10Show fewer
  • 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

Trial locations and contacts

No sites are listed yet.

About this study

Official title: Characterization of Vascular Functions in Myeloma Patients Before and During Anti-tumor Therapy

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:

Read more
  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. Patients with multiple myeloma have a limited endothelial function compared to a healthy control group.

A total of 40 myeloma patients will be examined. Measurements will be taken at baseline, 1 month and 6 month after myeloma therapy. Patients should not have received chemotherapy for at least 3 months. Furthermore a healthy sex- and age-matched control group will be examined.

Read the detailed description

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, many continue to live for more than 10 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.

Proteasome inhibitors including bortezomib and carfilzomib, and immunomodulatory agents, e.g. lenalidomide, represent cornerstone therapies for multiple myeloma. The most common therapy choices are Bortezomib-based therapy (VCD, VC) and Carfilzomib-based therapy (KRD, KD). Induction therapy is given 4-6 cycles followed by autologous hematopoietic cell transplantation. Thereafter, many patients receive consolidation therapy. In patients not eligible for autologous hematopoietic cell transplantation, a prolonged course of initial chemotherapy is typically administered. The proteasome inhibitor Bortezomib is used predominately in the front line setting, while second-generation carfilzomib is used in relapsed/refractory disease.

Despite their efficacy, increased rates of cardiovascular complications occur in patients exposed to these particular therapies. Higher incidences of cardiac adverse events including hypertension, arrhythmia, heart failure, ischemic heart disease and cardiomyopathy has been reported in patients receiving carfilzomib and bortezomib. Immunomodulatory agents are known to increase the risk of venous thromboembolic disease particularly when combined with dexamethasone or other chemotherapy. Furthermore, increased incidence of myocardial infarction (MI) and cerebrovascular events has been demonstrated in patients treated with lenalidomide. The mechanism of PI- and IMiD-associated cardiotoxicity is not fully elucidated. PIs inhibit proteasome activity, leading to the accumulation of abnormal proteins which in turn activates apoptotic pathways in myeloma cells. IMiDs bind cereblon, a component of the E3 ubiquitin ligase which promotes proteasome-mediated degradation of the transcription factors, IKZF1 and IKZF. It is unclear if the protein degradation properties of these drugs contribute to cardiotoxicity, although clinical features of the toxicity suggest endothelial cell injury and dysfunction. It is possible that CV events may be augmented when these two classes of medications are co-administered and further enhanced by the additional endothelial stress conferred by steroids. 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. 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. Patients with multiple myeloma have a limited endothelial function compared to a healthy control group.

Study design:

A total of 40 myeloma patients will be examined. Measurements will be taken at baseline, 1 month 6 month after myeloma therapy. Patients should not have received chemotherapy for at least 3 months. Furthermore a healthy sex- and age-matched control group will be examined.

Primary endpoint:

  • 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 endpoints:

  • Endothelial function, assessed by the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD) between baseline data in myeloma patients and control group
  • Change of left ventricular pump function (3D-EF, global longitudinal strain)
  • Alteration of echocardiographic parameters of diastolic dysfunction
  • Change in dyspnea symptoms (NYHA Classification)
  • Modification of cardiac biomarkers (NT-pro BNP, Troponin)
  • Change of circulating NO-Pool
  • Change in metabolomics (Biobank)
  • Change in arterial stiffness and augmentation index
  • Change of quality of life rated according to Medical Outcomes Short-Form Survey, SF-36, Minnesota Living With Heart Failure Questionnaire
  • Change in blood pressure
Being tested
Flow mediated dilation
Keywords
Myeloma, Flow mediated dilation, Endothelial Dysfunction, Proteasome inhibitors
Medical subject headings
Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Flow mediated dilationDiagnostic test

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

Study groups in NCT03776331
Study groupRoleWhat they receive
Myeloma PatientsNot described
Receives: Diagnostic Test: Flow mediated dilation
Controll groupNot described
Receives: Diagnostic Test: Flow mediated dilation

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: between baseline and 1 month data

Secondary outcomes (21)
  1. Change of endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD)

    Measured: between baseline and 6 month data

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

    Measured: between 1 and 6 month data

  3. 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

    Measured: baseline data

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

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

  5. Change of left ventricular pump function (global longitudinal strain)

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

  6. Alteration of grade of diastolic dysfunction

    Assesed by E, E/A, E/e', IVRT, DT, e', e'/a', TEI index, sPAP, according to ASE/EACVI GUIDELINES AND STANDARDS, Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging, Sherif et al, 2016, J Am Soc Echocardiogr, 2016

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

  7. Change in dyspnea symptoms (NYHA Classification)

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

  8. Change in concentration of Troponin

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

  9. Change in concentration of NT-pro BNP

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

  10. Change in circulating arginine-nitric oxide (NO) metabolites

    Levels of arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and N-monomethylarginine (MMA)

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

  11. Change in levels of circulating arginine

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

  12. Change in leves of circulating citrulline

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

  13. Change in levels of circulating ornithine

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

  14. Change in levels of circulating asymmetric dimethylarginine (ADMA)

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

  15. Change in levels of circulating symmetric dimethylarginine (SDMA)

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

  16. Change in levels of circulating N-monomethylarginine (MMA)

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

  17. Change in pulse wave velocity as a parameter of arterial stiffness

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

  18. Change in augmentation index

    Augmentation index (AIx), the pressure difference between the shoulder on the pressure wave and systolic pressure expressed as a ratio of pulse pressure is widely used as a proxy of wave reflection

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

  19. Change of quality of life rated according to Minnesota Living With Heart Failure Questionnaire

    The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (zero) to 5 scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. The questionnaire is simply scored by summation of all 21 responses.

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

  20. Change of quality of life rated according to Medical Outcomes Short-Form Survey

    The SF-36 consists of 36 questions and is a general health questionnaire that provides information about the health status of the patient through 8 different dimensions. He makes statements about:

    General Health Perception, Physical Health, Restricted physical role function, Physical pain, Vitality, Mental Healt, Restricted emotional role function, Social functioning. For the evaluation of the SF-36 questionnaire v1.0 you first recode all answers in predefined points using a recoding table. Then you calculate the average score of all questions of the respective health dimension, e.g. physical health, so you have 8 average points for the 8 dimensions. These 8 scores now describe the health status of the patient in their respective dimensions, which can then be assessed using comparison charts.

    The possible score ranges from 0 to 100 points. 0 points represent the greatest possible restriction of health, while 100 points represent the absence of health restrictions.

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

  21. Change in blood pressure (systolic, diastolic and MAD)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2018
  2. Study start28 Dec 2018 (estimated)
  3. Primary completion28 Dec 2019 (estimated)
  4. Study completion28 Mar 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
96 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03776331
Sponsor's protocol ID
Vascular-Myelom
Status last verified
Dec 2018
First submitted
10 Nov 2018
Last updated
19 Dec 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

An observational study of Cardiooncology and Myeloma, run by University Hospital, Essen.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Matthias Totzeck (004920172384805, matthias.totzeck@uk-essen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD) (time frame: between baseline and 1 month data). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2018.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in