Evaluation of Acute and Chronic Nephrotoxicity in Acute Lymphatic Leukemia Patients Using Ultrasound Localization Microscopy

NCT ID: NCT07313878

Last Updated: 2026-01-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-19
• Study Completion Date: 2026-11-30

Brief Summary

With increasing survival rates in pediatric oncology, reports of long-term side effects persisting decades after treatment are also rising. Clinically evident nephropathies occur in about 5.5% of survivors more than five years after therapy. Chemotherapeutic agents such as ifosfamide, cisplatin, and carboplatin, as well as kidney-directed treatments like radiation, surgery, or stem cell transplantation, increase this risk. Acute kidney injury has also been described in association with cyclophosphamide and high-dose methotrexate, which are used in the treatment of acute lymphoblastic leukemia (ALL). Studies show a high prevalence of albuminuria (around 14.5% of childhood cancer survivors), an early marker of kidney damage, while standard parameters like creatinine often become abnormal only at later stages.

Leukemia survivors suffer from vascular late effects caused by persistent endothelial damage triggered by cancer therapies such as anthracyclines, cyclophosphamide, and asparaginase, which increase inflammation and thrombosis risk. These vascular changes may also contribute to kidney injury.

ULM is a high-resolution ultrasound technique that uses microbubbles to visualize the microvasculature and resolve dynamic blood flow changes with a resolution beyond the diffraction limit. ULM is independent of kidney or liver function, has been applied in various organs, and was recently used for the first time to visualize glomeruli-the smallest functional units of the kidney-in humans. This method enables early detection of glomerular injury as a consequence of vascular damage, even before albuminuria appears, potentially allowing earlier adaptation of follow-up and initiation of treatment.

This pilot project focuses on survivors of ALL, as they are the largest and best studied pediatric cancer patient group also regarding late effects and, therefore, a sufficient number of individuals can be expected for his monocentric approach. Vascular functional impairment of the kidney could be detected at an early stage and the follow-up structures and measures such as the early use of nephroprotective drugs could be adapted.

Conditions

Acute Lymphoblastic Leukaemias (ALL); Long Term Follow-Up

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Early therapeutic effects

• Diagnosed acute lymphatic leukemia
• Treatment day < 50 according to therapy protocol / no administration of CPM before first examination
• From 3 years to < 18 years

Group Type: EXPERIMENTAL

Ultrasound Localization Microscopy (ULM)

Intervention Type: DIAGNOSTIC_TEST

Single Examination: ULM of the kidney after application of a contrast medium (SonoVue®, intravenous).

Blood sample

Intervention Type: DIAGNOSTIC_TEST

Blood draw (including BB, Diff, Glucose, Na, K, Cl, Ca, LDH, Crea, Cystatin C, Uric Acid, CRP, Albumin, Ferritin, Total Protein) through venous access.

Urinanalysis

Intervention Type: DIAGNOSTIC_TEST

Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes.

Renal sonography

Intervention Type: DIAGNOSTIC_TEST

Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others.

Late therapeutic effects

• Diagnosed acute lymphatic leukemia
• Completed oncological treatment
• From 3 years to < 18 years

Group Type: EXPERIMENTAL

Ultrasound Localization Microscopy (ULM)

Intervention Type: DIAGNOSTIC_TEST

ULM of the kidney after application of a contrast medium (SonoVue®, intravenous) at two different time points:

Timepoint 1: Before initiation of therapy, latest day 50 before 1st high-dose methotrexate or cyclophosphamide.

Timepoint 2: After termination of intensive treatment (after 6-9 months).

Blood sample

Intervention Type: DIAGNOSTIC_TEST

Blood draw (including BB, Diff, Glucose, Na, K, Cl, Ca, LDH, Crea, Cystatin C, Uric Acid, CRP, Albumin, Ferritin, Total Protein) through venous access at Timepoint 1 and 2.

Urinanalysis

Intervention Type: DIAGNOSTIC_TEST

Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes at Timepoint 1 and Timepoint 2.

Renal sonography

Intervention Type: DIAGNOSTIC_TEST

Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others at time point 1 and time point 2.

Interventions

Ultrasound Localization Microscopy (ULM)

Single Examination: ULM of the kidney after application of a contrast medium (SonoVue®, intravenous).

Intervention Type: DIAGNOSTIC_TEST

Ultrasound Localization Microscopy (ULM)

ULM of the kidney after application of a contrast medium (SonoVue®, intravenous) at two different time points:

Timepoint 1: Before initiation of therapy, latest day 50 before 1st high-dose methotrexate or cyclophosphamide.

Timepoint 2: After termination of intensive treatment (after 6-9 months).

Intervention Type: DIAGNOSTIC_TEST

Blood sample

Blood draw (including BB, Diff, Glucose, Na, K, Cl, Ca, LDH, Crea, Cystatin C, Uric Acid, CRP, Albumin, Ferritin, Total Protein) through venous access.

Intervention Type: DIAGNOSTIC_TEST

Blood sample

Blood draw (including BB, Diff, Glucose, Na, K, Cl, Ca, LDH, Crea, Cystatin C, Uric Acid, CRP, Albumin, Ferritin, Total Protein) through venous access at Timepoint 1 and 2.

Intervention Type: DIAGNOSTIC_TEST

Urinanalysis

Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes.

Intervention Type: DIAGNOSTIC_TEST

Urinanalysis

Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes at Timepoint 1 and Timepoint 2.

Intervention Type: DIAGNOSTIC_TEST

Renal sonography

Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others.

Intervention Type: DIAGNOSTIC_TEST

Renal sonography

Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others at time point 1 and time point 2.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Diagnosed acute lymphatic leukemia
• From 3 years to < 18 years
• completed oncological treatment or treatment day < 50 according to therapy protocol and no administration of CPM before first examination.

Exclusion Criteria

• Known allergic disposition to SonoVue / other contrast agents
• Tattoo in the area of the examination field
• Pregnancy
• Breastfeeding mothers
• Contraindication for the use of Sonovue
• Critical condition
• Known clinically evident renal impairment

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of Pediatrics and Adolescent Medicine

Erlangen, Baveria, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Axel Karow, MD

Role: CONTACT

axel.karow@uk-erlangen.de

+4991318533118

Alexander Dierl, MD

Role: CONTACT

alexander.dierl@uk-erlangen.de

+4991318533118

Facility Contacts

Axel Karow, MD

Role: primary

axel.karow@uk-erlangen.de

+49 9131 8533118

Alexander Dierl, MD

Role: backup

alexander.dierl@uk-erlangen.de

+4991318533118

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

HEALED-ULM

Identifier Type: -

Identifier Source: org_study_id