Atypical Hemolytic Uremic SyndromeaHUS-iPSC-ECNCT05805202
Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy
A study testing Blood sampling and urine analysis in people with Atypical Hemolytic Uremic Syndrome, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Atypical Hemolytic Uremic Syndrome
- What is being tested?
- Blood sampling and urine analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 1 siteItaly
- Study dates
- 3 May 2023to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"
Ranica, BG, 24020
Erica Daina, 0039 035 45351, erica.daina@marionegri.it
About this study
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.
Read more
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
- Conditions
- Atypical Hemolytic Uremic Syndrome
- Being tested
- Blood sampling and urine analysis
- Keywords
- Atypical hemolytic uremic syndrome, Induced pluripotent stem cells, Endothelial cells, Alternative complement pathway, Eculizumab, Drug screening (in vitro)
- Medical subject headings
- Atypical Hemolytic Uremic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampling and urine analysisOther
A blood sample of 10- 20 ml from pediatric patients, 30-50 ml from adult patients will be collected for each patient and healthy voluntarees
| Study group | Role | What they receive |
|---|---|---|
| aHUS Patient | Experimental | The study will include 110 patients consenting adult and pediatric patients with a diagnosis of atypical hemolytic uremic syndrome and carrying mutations in the MCP or DGKE genes. New patients will be selected through clinical and genetic screening of the inhabitants of a small island of South Italy (Linosa) with high incidence of patients affected by DGKE mutations and characterized by a high rate of endogamy Receives: Other: Blood sampling and urine analysis |
| Healthy volunteer | Other | 2 healthy subjects will undergo urine analysis (multistick) and only subjects with normal parameters will be enrolled as controls. Receives: Other: Blood sampling and urine analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Generation and characterization of patient-specific and healthy donor iPSC
Measured: once during the study
Differentiation of iPSC into endothelial cells
Measured: once during the study
Characterizationof iPSC into endothelial cells
Measured: once during the study
Cell culture viability
Measured: once during the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2023
- Study start3 May 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atypical Hemolytic Uremic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mario Negri Institute for Pharmacological Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05805202
- Sponsor's protocol ID
- aHUS-iPSC-EC
- Acronym
- aHUS-iPSC-EC
- Status last verified
- Sep 2025
- First submitted
- 28 Mar 2023
- Last updated
- 29 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy
- ClinicalTrials.gov ID
- NCT05805202
- Acronym / sponsor ID
- aHUS-iPSC-EC / aHUS-iPSC-EC
- Conditions
- Atypical Hemolytic Uremic Syndrome
- Keywords
- Atypical hemolytic uremic syndrome, Induced pluripotent stem cells, Endothelial cells, Alternative complement pathway, Eculizumab, Drug screening (in vitro)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- 3 May 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 7 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| aHUS Patient | Experimental | Other: Blood sampling and urine analysisThe study will include 110 patients consenting adult and pediatric patients with a diagnosis of atypical hemolytic uremic syndrome and carrying mutations in the MCP or DGKE genes. New patients will be selected through clinical and genetic screening of the inhabitants of a small island of South Italy (Linosa) with high incidence of patients affected by DGKE mutations and characterized by a high rate of endogamy |
| Healthy volunteer | Other | Other: Blood sampling and urine analysis2 healthy subjects will undergo urine analysis (multistick) and only subjects with normal parameters will be enrolled as controls. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (3 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood sampling and urine analysisA blood sample of 10- 20 ml from pediatric patients, 30-50 ml from adult patients will be collected for each patient and healthy voluntarees | Other | Healthy volunteer, aHUS Patient |
Primary outcome
Generation and characterization of patient-specific and healthy donor iPSC
Time frame: once during the study
Differentiation of iPSC into endothelial cells
Time frame: once during the study
Characterizationof iPSC into endothelial cells
Time frame: once during the study
Cell culture viability
Time frame: once during the study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sampling and urine analysis in people with Atypical Hemolytic Uremic Syndrome, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marina Noris, Dr. (+3903545351, marina.noris@marionegri.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Generation and characterization of patient-specific and healthy donor iPSC (time frame: once during the study). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2025; AzTrials last refreshed its copy on 26 Oct 2026.