Sunitinib Treatment on Tissue Sodium Accumulation (TSS2)

January 25, 2021 updated by: Dr. Lajos Marko, Charite University, Berlin, Germany

Effect of Sunitinib Treatment on Tissue Sodium Accumulation in Patients With Renal Cancer: a Pilot Study

Here, it is investigated how sunitinib, a tyrosine kinase-inhibitor targeting vascular endothelial growth factor receptors, might influence sodium homeostasis in the skin and if this is related to a well-described treatment side-effect of sunitinib, hypertension.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Tyrosine kinases-inhibitors targeting vascular endothelial growth factor (VEGF)-receptors (RTKIs) are increasingly used in oncology in several metastatic tumor types. These agents are featured by toxicities including hypertension. According to a new insight, sodium in response to a high dietary sodium intake, is accumulated in a hyperosmolar way in the interstitial compartment. In response to this high sodium concentration cells of the mononuclear phagocytic system (MPS) are activated resulting in an increased production of VEGF-C, activation of VEGF type 3 receptors and formation of a lymphatic capillary network, involved in clearance of interstitial sodium. Blockade of stimulation of VEGF-C receptors or depletion of MPS cells in rodents has been associated with salt-sensitive hypertension.

Sunitinib is an orally-active, multitarget RTKI mainly used for the treatment of patients with metastatic renal cancer and imatinib-resistant gastrointestinal stromal tumors. Sunitinib blocks all three VEGF receptors subtypes, including VEGF-receptor type 3.

The investigators hypothesize that treatment of patients with sunitinib is associated with tissue sodium accumulation and this accumulation contributes to the rise in blood pressure. Tissue sodium is measured by using a newly developed 23Na magnetic resonance-imaging (MRI) technique which allows a non-invasive and contrast agent-free sodium content measurement in the muscle and skin of the lower leg.

Study Type

Observational

Enrollment (Actual)

6

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 13125
        • Experimental and Clinical Research Center, Clinical Research Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

Patients with metastatic renal cell carcinome in the primary care of the Charité - Universitätsmedizin Berlin as well as healthy subjects without known disease recruited in the Charité - Universitätsmedizin Berlin and healthy volunteers form the Max-Delbrück Center of Molecular Medicine

Description

Inclusion Criteria:

  • Age men > 18 years
  • Life-expectation > 3 months
  • Stable weight
  • Blood pressure below 140/90 mmHg at baseline
  • Estimated glomerular filtration rate > 45 ml/min/1.73m2
  • Willingness to give written informed consent

Exclusion Criteria:

  • Heart failure
  • Liver disease with ascites
  • Nephrotic syndrome
  • Gastrointestinal complaints, preventing normal daily food intake or diarrhea
  • Any form of diabetes mellitus
  • Known autoimmune diseases
  • Acute or chronic infection
  • Alcohol or substance abuse

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients
Metastatic cell carcinoma patients before sunitinib treatment, after 4 week on, after 2 week off and finally again 4 week on medication.
Drug: Sunitinib
Other Names:
  • Diagnostic test: 23Na-MRI
Healthy controls
Age-matched subjects without known disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Skin sodium
Time Frame: 3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)
Changes in sodium content measured by 23Na magnetic resonance-imaging (MRI) technique
3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma VEGF-C
Time Frame: 3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)
Concentration of VEGF-C in patients plasma
3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charite University, Berlin, Germany

Collaborators

German Heart Institute

Investigators

  • Study Director: Dominik Müller, PhD, Group leader at the Max Delbruck Center for Molecular Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2015

Primary Completion (Actual)

February 1, 2019

Study Completion (Actual)

March 1, 2020

Study Registration Dates

First Submitted

April 27, 2020

First Submitted That Met QC Criteria

April 27, 2020

First Posted (Actual)

April 29, 2020

Study Record Updates

Last Update Posted (Actual)

January 27, 2021

Last Update Submitted That Met QC Criteria

January 25, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ChariteU-ECRC-TSS2
  • EA1/044/15 (Other Identifier: Ethics Committee of the Charité - Universitätsmedizin Berlin)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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