Sunitinib Treatment on Tissue Sodium Accumulation (TSS2)

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04368546
• Other study ID #: ChariteU-ECRC-TSS2
• Secondary ID: EA1/044/15
• Status: Completed
• Start date: November 1, 2015
• Est. completion date: March 1, 2020

Study information

• Verified date: January 2021
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: March 1, 2020
• Est. primary completion date: February 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Hypertension
• Renal Cell Cancer Metastatic
• Sodium Imbalance

Intervention

Drug:
• Sunitinib

Locations

Country	Name	City	State
Germany	Experimental and Clinical Research Center, Clinical Research Unit	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	German Heart Institute

Country where clinical trial is conducted

Germany, 

References & Publications (4)

Kandula P, Agarwal R. Proteinuria and hypertension with tyrosine kinase inhibitors. Kidney Int. 2011 Dec;80(12):1271-7. doi: 10.1038/ki.2011.288. Epub 2011 Sep 7. Review. — View Citation

Kappers MH, van Esch JH, Sluiter W, Sleijfer S, Danser AH, van den Meiracker AH. Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels. Hypertension. 2010 Oct;56(4):675-81. doi: 10.1161/HYPERTENSIONAHA.109.149690. Epub 2010 Aug 23. — View Citation

Kopp C, Linz P, Dahlmann A, Hammon M, Jantsch J, Müller DN, Schmieder RE, Cavallaro A, Eckardt KU, Uder M, Luft FC, Titze J. 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension. 2013 Mar;61(3):635-40. doi: 10.1161/HYPERTENSIONAHA.111.00566. Epub 2013 Jan 21. — View Citation

Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, Park JK, Beck FX, Müller DN, Derer W, Goss J, Ziomber A, Dietsch P, Wagner H, van Rooijen N, Kurtz A, Hilgers KF, Alitalo K, Eckardt KU, Luft FC, Kerjaschki D, Titze J. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009 May;15(5):545-52. doi: 10.1038/nm.1960. Epub 2009 May 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Skin sodium	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	Plasma VEGF-C	Concentration of VEGF-C in patients plasma	3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)