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Sunitinib Treatment on Tissue Sodium Accumulation (TSS2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04368546
Recruitment Status : Active, not recruiting
First Posted : April 29, 2020
Last Update Posted : April 30, 2020
Sponsor:
Collaborator:
German Heart Institute
Information provided by (Responsible Party):
Dr. Lajos Marko, Charite University, Berlin, Germany

Brief Summary:
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.

Condition or disease Intervention/treatment
Renal Cell Cancer Metastatic Hypertension Sodium Imbalance Drug: Sunitinib

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.

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Study Type : Observational
Actual Enrollment : 6 participants
Observational Model: Case-Crossover
Time Perspective: Prospective
Official Title: Effect of Sunitinib Treatment on Tissue Sodium Accumulation in Patients With Renal Cancer: a Pilot Study
Actual Study Start Date : November 1, 2015
Actual Primary Completion Date : February 1, 2019
Estimated Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine


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 Name: Diagnostic test: 23Na-MRI

Healthy controls
Age-matched subjects without known disease.



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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


Biospecimen Retention:   Samples Without DNA
Blood plasma


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   The effect of the female hormonal cycle on skin sodium homeostasis is unknown, therefore we include here male subjects only.
Accepts Healthy Volunteers:   Yes
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
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04368546


Locations
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Germany
Experimental and Clinical Research Center, Clinical Research Unit
Berlin, Germany, 13125
Sponsors and Collaborators
Charite University, Berlin, Germany
German Heart Institute
Investigators
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Study Director: Dominik Müller, PhD Group leader at the Max Delbruck Center for Molecular Medicine
Publications:
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Responsible Party: Dr. Lajos Marko, MD, PhD, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT04368546    
Other Study ID Numbers: ChariteU-ECRC-TSS2
EA1/044/15 ( Other Identifier: Ethics Committee of the Charité - Universitätsmedizin Berlin )
First Posted: April 29, 2020    Key Record Dates
Last Update Posted: April 30, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Dr. Lajos Marko, Charite University, Berlin, Germany:
Sunitinib
Tyrosine kinases-inhibitor
Sodium
MRI
Skin
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sunitinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action