ClinicalTrials.gov record NCT05805202

Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Aug 22, 2026

Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
Healthy volunteersAcceptedPeople who do not have the condition being studied who are allowed to take part. Some studies include both people with the condition and healthy volunteers; others may enrol only healthy volunteers.
SexAll
LocationItaly
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This study collects blood and urine from people with atypical hemolytic uremic syndrome (aHUS) and a small group of healthy controls. Researchers will make induced pluripotent stem cells (iPSC) from participants' blood, turn them into endothelial cells, and study those cells in the laboratory. The project focuses on rare MCP and DGKE gene mutations and includes laboratory drug screening to identify compounds that correct any cellular abnormalities.

What it is studying. The study tests whether endothelial cells grown from participants' own induced pluripotent stem cells (iPSC) show functional differences linked to MCP or DGKE gene mutations. It also screens those lab-grown cells to identify compounds that might correct observed abnormalities. Outcomes include creating and characterizing patient and donor iPSC, differentiating them into endothelial cells, and measuring cell viability and function.

What the researchers hope to learn. Scientific goals: generate and characterize patient-specific and control iPSC; produce and study iPSC-derived endothelial cells; measure cell culture viability and functional abnormalities linked to MCP and DGKE mutations; and perform in vitro drug screening to identify compounds that correct cellular defects.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

Hemolytic Uremic Syndrome (HUS) is a rare disease characterized by rupture of red blood cells (hemolytic anemia), low platelet count (thrombocytopenia), and thrombotic occlusion of small vessels (thrombotic microangiopathy), with prevalent involvement of the kidneys. SEU, in its typical form is caused by gastrointestinal infection with Escherichia coli. The atypical form of SEU (aSEU), which is not caused by an Escherichia coli infection, is a very rare disease that may have a genetic origin; it affects both children and adults and may occur in a sporadic or familial form. Many studies have shown that about 60% of cases of atypical HUS are associated with genetic abnormalities of the complement system (particularly the so-called "alternative pathway"), which is a key part of the immune system for responding to infection. Complement consists of a series of proteins that, when activated, create a so-called "cascade," which leads to the elimination of the infectious agent, either directly or through other cells. Complement is finely regulated in such a way as to prevent damage to healthy cells in one's own body. Genetic defects in some of these complement regulatory proteins cause reduced protection of the endothelial surface (thus the vessel wall) against complement activation. Recently, new mutations have been described in a gene unrelated to the complement pathway, the DKGE gene, which codes for the intracellular isoform of diacylglycerol kinase . In these patients, small renal vessel occlusion appears to occur as a result of altered endothelial cell proliferation and angiogenesis through mechanisms apparently unrelated to complement activation. However, to date these mechanisms are poorly studied. Throughout the entire project statistical methods will be applied to optimize the characterization of the abnormalities in phenotype and function of iPSC-EC derived from aHUS patients with either DGKE or MCP genetic abnormalities as compared with control iPSC-EC, including identifying potential drugs that could correct the abnormalities

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Other
  • Blood sampling and urine analysis

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Adults and children with aHUS defined by history of microangiopathic hemolytic anemia and thrombocytopenia (hematocrit (Ht) <30%, hemoglobin (Hb) <10 g/dL, LDH >500 IU/L, undetectable haptoglobin, fragmented erythrocytes in the peripheral blood smear with negative Coomb's test, and platelet count <150,000/microL), associated with acute renal failure.
  • Written informed consent

Exclusion criteria

  • TTP (ADAMTS13 activity <10%)
  • STEC-HUS (presence of stx and eae genes or Shiga-toxin in the stools and/or serum antibodies against Shiga-toxin and/or STEC LPS).
  • Disseminated intravascular coagulation (prolonged thromboplastin time and lower than normal fibrinogen levels).

Study description and what participation involves

The registry record has no detailed description beyond the summary above.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants will provide blood and urine samples (about 10–20 mL blood for children and 30–50 mL for adults, and urine testing). Healthy volunteers will have a urine multistick and, if normal, may be enrolled as controls and provide blood. Samples will be used in the laboratory to generate and characterize patient-specific induced pluripotent stem cells (iPSC) and to differentiate and study iPSC-derived endothelial cells. The registry record does not list other procedures or a detailed visit schedule.

How the study is structured. Interventional study with two parallel groups: people with aHUS (carrying MCP or DGKE mutations) and a very small healthy control group. Participants provide blood and urine samples; researchers make patient-specific iPSC, differentiate them into endothelial cells, and run laboratory tests and in vitro drug screening. The study is non-randomized and open-label (no masking).

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in Italy. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on atypical hemolytic uremic syndrome

Clinical trials13 trials listed for atypical hemolytic uremic syndromeEvery trial the registry lists for atypical hemolytic uremic syndrome, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in atypical hemolytic uremic syndrome researchLatest monthly update: September 2026. Includes: Ravulizumab and labs. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
May 3, 2023
Primary completion
Dec 31, 2026 (estimated)
Study completion
Dec 31, 2026 (estimated)
Target enrollment
112 participants (estimated)
Last updated on registry
Sep 29, 2025
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Mario Negri Institute for Pharmacological Research

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

Written informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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