Alport SyndromeAlport-XXLNCT02378805
Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome
An observational study of Alport Syndrome and Hereditary Kidney Disease, run by University Hospital Goettingen at 1 site in Germany.
Trial summary
The hereditary type IV collagen disease Alport syndrome leads to kidney failure early in life. Currently there are no specific medications approved for treatment, however, several therapies have been evaluated preclinically and could improve outcome. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Alport Syndrome, Hereditary Kidney Disease, Pediatric Kidney Disease
- What is being tested?
- ACE-inhibitor, Angiotensin-receptor blocker (ARB) and HMG-Coenzyme inhibitor (statin)
- Type of treatment
- Injection or infusion
- How many people
- 800 participants
- Where
- 1 siteGermany
- Study dates
- Jul 1995to 1 Mar 2036
- How long will I take part?
- 30 Years
- Phase
- Observational
- 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
Study population: For Alport XXL, eligible patients were children or young adults with a definitive diagnosis of AS by genetic analysis or kidney biopsy and at early stages of AS (stages 0, I or II) at baseline. AS stages were defined as: Stage 0 Microhematuria without microalbuminuria Stage I Microalbuminuria: UACR 30-300 mg/gCreatinine Stage II Proteinuria: UACR >300 with eGFR>60 ml/min/1.73m2 Stage III eGFR<60 ml/min/1.73m2 Stage IV end stage kidney failure Stage V death (from all causes)
Who may be able to join
- Diagnosis of Alport syndrome (AS) by kidney biopsy or mutation analysis (or both).
- Any type of genetic variant is accepted for X-linked, autosomal or digenic Alport syndrome (COL4A3, 4 or 5 genes).
Who cannot join
- Patients not willing to give informed consent. Patient with suspected diagnosis, whcih cannot be confirmed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
University Medical Center Göttingen
Göttingen, Lower Saxony, 37075
Oliver Gross, MD, +49-551-39- ext. 60488, gross.oliver@med.uni-goettingen.de
About this study
Official title: European Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome: Current and Novel Therapies
The hereditary type IV collagen disease Alport syndrome leads to kidney failure early in life. Currently there are no specific medications approved for treatment, however, several therapies have been evaluated preclinically and could improve outcome. For that reason, this non-interventional, observational study investigates, if medications (1) delay disease progression; (2) delay time to kidney failure; (3) improve life-expectancy compared to untreated patients (relatives). This observational study started in 2006 as an European registry. Since 2019, this registry has been expanded to "Alport XXL" via the International Alport Alliance as a global effort across all continents. From 2020 on to present, "Alport XXL" has a special focus on the outcomes of early therapy in young patients on ACE-inhibitors vs. Angiotensin-receptor blockers vs. their combination.
Read the detailed description
Early diagnosis in children with Alport syndrome (AS) with isolated hematuria opens a "window of opportunity" for early intervention. In the Alport mouse-model, this early intervention with the ACE-inhibitor Ramipril let to a delay of kidney failure by 111%. In order to observe treatment approaches for AS in humans, this registry has been established in 2006 to collect data over several generations of Alport families across Europe. In the meantime, this registry has been expanded to "Alport XXL" via the International Alport Alliance as a global effort across all continents.
Small children with AS first develop microscopic hematuria (stage 0), proceeding to microalbuminuria (stage I), overt proteinuria (stage II), impaired kidney function (stage III) and finally can end up with kidney failure (stage IV), leading to impaired quality of life and premature death (stage V). This registry uses these stages to assess if earlier initiation of medications such as ACE-inhibition at earlier stages of disease is more effective than later therapy in delaying the time to disease progression (doubeling or tripeling of albuminuria), delaying loss of estimated glomerular filtration rate (eGFR), and if therapy improves life-expectancy.
Untreated children with autosomal-recessive AS, digenic AS, and boys with X-linked AS typically all develop kidney failure early in life. Untreated girls with X-linked AS have a 30-40% risk of kidney failure, typically later in life (40 years or older). Untreated heterozygous patients with COL4A3/COL4A4 variants typically have a less severe phenotype (in former times also called "familial benign hematuria" or "thin basement membrane nephropathy" (TBMN)) and a 1-2% risk of kidney failure.
Several interim results of this registry have been published since 2012.
Alport XXL is designed and conducted as strictly observational, non-interventional data acquisition with prospective (and in parts retrospective) data analysis. Young patients with AS in disease stages 0,I,II from all over the world are included. The renewed version from 2021 has been re-approved by the Ethics Committee of the University Medical Center Göttingen as "Alport XXL", a further development of the former European Alport Therapy Registry (AZ 10/11/06). "Alport XXL" registry and data storage are in conformity with Good Clinical Practice guidelines.
ICH-GCP-conform patient information and data exchange is secured by data transfer and cooperation agreements between all international trial centers and the coordinating principal investigator at University Medical Center Goettingen. At baseline, data collection including retrospective data is performed using a standardized, ICH-GCP-conform and pseudonymized questionnaire assessing age, sex, weight, height, mode of inheritance (X-linked, autosomal, compound heterozygous/homozygous, number of missense variants), family history, albumin in 24-hour or spontaneous urine, serum-creatinine, RAS-blockade with preparation and dose. Follow-up visits include same data than baseline plus blood-pressure, smoking-status, serum-potassium, eGFR, hearing loss and eye involvement, other symptoms such as leiomyomatosis, comorbidities and adverse events (adverse events of special interest defined as hyperkalemia, cough, hypotension, acute renal failure, malignancy, death).
- Conditions
- Alport Syndrome, Hereditary Kidney Disease, Pediatric Kidney Disease, Thin Basement Membrane Disease, Familial Benign Hematuria
- Being tested
- ACE-inhibitor, Angiotensin-receptor blocker (ARB), HMG-Coenzyme inhibitor (statin), Spironolactone or Finerenone, Paricalcitol
- Keywords
- Alport syndrome, thin basement membrane disease, familial benign hematuria
- Medical subject headings
- Nephritis, Hereditary, Hematuria, Benign Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACE-inhibitorDrug
observational study
Angiotensin-receptor blocker (ARB)Drug
observational study
HMG-Coenzyme inhibitor (statin)Drug
observational study
Spironolactone or FinerenoneDrug
observational study
ParicalcitolDrug
observational study!
SGLT2 inhibitorDrug
observational study
| Study group | Role | What they receive |
|---|---|---|
| no-T: untreated patients | untreated patients, typically uncles or grandfathers of present patients. No Intervention (means no therapy until CKD stage V, on renal replacement therapy) | |
| T-III: late therapy in patients | patients treated with medications with low eGFR (below 60 ml/min) (starts at patients with CKD stages III and IV). Receives: Drug: ACE-inhibitor; Drug: Angiotensin-receptor blocker (ARB); Drug: HMG-Coenzyme inhibitor (statin); Drug: Spironolactone or Finerenone; Drug: Paricalcitol; Drug: SGLT2 inhibitor | |
| T-II: early therapy in patients | therapy starts in patients with albuminuria >300mg/gCreatinine and eGFR higher than 60 ml/min. Receives: Drug: ACE-inhibitor; Drug: Angiotensin-receptor blocker (ARB); Drug: HMG-Coenzyme inhibitor (statin); Drug: Spironolactone or Finerenone; Drug: Paricalcitol; Drug: SGLT2 inhibitor | |
| T-I: very early therapy in patients | therapy starts in patients with microhematuria only (usually at birth) or microalbuminuria (30-300 mg albumin per gCreatinine). Receives: Drug: ACE-inhibitor; Drug: Angiotensin-receptor blocker (ARB); Drug: HMG-Coenzyme inhibitor (statin); Drug: Spironolactone or Finerenone; Drug: Paricalcitol; Drug: SGLT2 inhibitor | |
| no therapy in heterozygous patients | heterozygous patients without therapy | |
| therapy in heterozygous patients | heterozygous patients with therapy (which also can be divided into subgroups stage T-0, I, II, III) Receives: Drug: ACE-inhibitor; Drug: Angiotensin-receptor blocker (ARB); Drug: HMG-Coenzyme inhibitor (statin); Drug: Spironolactone or Finerenone; Drug: Paricalcitol; Drug: SGLT2 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
age at onset of end stage kidney failure (need for renal replacement therapy)
kidney disease in Alport syndrome starts at birth, age at onset of end stage kidney failure in years
Measured: until end of observation in 2037
life-expectancy in years (age at death)
Alport syndrome starts at birth, age at death of patients in years
Measured: until end of observation in 2037
yearly loss of estimated glomerular filtration rate (eGFR)
kidney disease in Alport syndrome starts at birth, eGFR-loss per year in ml/min/1.73m2
Measured: until end of observation in 2037
time in years until doubling or tripling of urinary albumin to creatinine ratio (UACR)
kidney disease in Alport syndrome starts at birth; time since birth to doubling (AS stages I or II) or tripling (AS stage 0) of UACR in years.
Measured: until end of observation in 2037
Secondary outcomes (8)
amount of albuminuria over time
kidney disease in Alport syndrome starts at birth; change in albuminuria after birth
Measured: until end of observation in 2037
amount of proteinuria over time
kidney disease in Alport syndrome starts at birth; change in proteinuria after birth
Measured: until end of observation in 2037
number of patients with X-chromosomal or autosomal inheritance
specific genetic variant: X-linked, digenic, autosomal heterozygous, homozygous, compound heterozygous
Measured: until end of observation in 2037
number of patients experiencing side effects (AEs)
AEs of special interest: acute kidney renal failure, angioedema, hyperkalemia, dry cough, symptomatic hypotension (orthostatic collapse) and others, and death from all causes.
Measured: until end of observation in 2037
number of patients with hearing loss
Alport syndrome is a genetic disease, hearing loss delevops over time since birth
Measured: until end of observation in 2037
number of patients with eye involvement
Alport syndrome is a genetic disease, eye symptoms delevop over time since birth
Measured: until end of observation in 2037
number of patients with positive family history of end stage kidney failure
number of relatives with kidney failure
Measured: until end of observation in 2037
age of relatives at end stage kidney failure
age of relatives at start of renal replacement therapy in years
Measured: until end of observation in 2037
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2015 (estimated)
- Study startJul 1995
- Primary completion1 Mar 2036 (estimated)
- Study completion1 Mar 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Alport 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 800 participants (estimated)
- Target duration
- 30 Years
Sponsor and investigators
- Lead sponsor
- University Hospital Goettingen
- Sponsor type
- University, hospital or other
- Collaborators
- Society for Pediatric Nephrology (Germany)
- Responsible party
- Principal investigator, Prof. Dr. O. Gross, University Hospital Goettingen
- Investigators
- Oliver Gross, MD, Principal investigator, University Hospital Goettingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02378805
- Sponsor's protocol ID
- Alport-UMG2010
- Acronym
- Alport-XXL
- Status last verified
- Mar 2025
- First submitted
- 26 Feb 2015
- Last updated
- 6 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Investigators plan to share the full data set with other researchers upon reasonable request via written cooperation agreements.
Publications
Kashtan CE, Gross O. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol. 2021 Mar;36(3):711-719. doi: 10.1007/s00467-020-04819-6. Epub 2020 Nov 6.
PubMed 33159213Weinstock BA, Feldman DL, Fornoni A, Gross O, Kashtan CE, Lagas S, Lennon R, Miner JH, Rheault MN, Simon JF; Workshop Participants. Clinical trial recommendations for potential Alport syndrome therapies. Kidney Int. 2020 Jun;97(6):1109-1116. doi: 10.1016/j.kint.2020.02.029. Epub 2020 Apr 6.
PubMed 32386680Temme J, Kramer A, Jager KJ, Lange K, Peters F, Muller GA, Kramar R, Heaf JG, Finne P, Palsson R, Reisaeter AV, Hoitsma AJ, Metcalfe W, Postorino M, Zurriaga O, Santos JP, Ravani P, Jarraya F, Verrina E, Dekker FW, Gross O. Outcomes of male patients with Alport syndrome undergoing renal replacement therapy. Clin J Am Soc Nephrol. 2012 Dec;7(12):1969-76. doi: 10.2215/CJN.02190312. Epub 2012 Sep 20.
PubMed 22997344Temme J, Peters F, Lange K, Pirson Y, Heidet L, Torra R, Grunfeld JP, Weber M, Licht C, Muller GA, Gross O. Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations. Kidney Int. 2012 Apr;81(8):779-83. doi: 10.1038/ki.2011.452. Epub 2012 Jan 11.
PubMed 22237748Gross O, Licht C, Anders HJ, Hoppe B, Beck B, Tonshoff B, Hocker B, Wygoda S, Ehrich JH, Pape L, Konrad M, Rascher W, Dotsch J, Muller-Wiefel DE, Hoyer P; Study Group Members of the Gesellschaft fur Padiatrische Nephrologie; Knebelmann B, Pirson Y, Grunfeld JP, Niaudet P, Cochat P, Heidet L, Lebbah S, Torra R, Friede T, Lange K, Muller GA, Weber M. Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int. 2012 Mar;81(5):494-501. doi: 10.1038/ki.2011.407. Epub 2011 Dec 14.
PubMed 22166847Stock J, Kuenanz J, Glonke N, Sonntag J, Frese J, Tonshoff B, Hocker B, Hoppe B, Feldkotter M, Pape L, Lerch C, Wygoda S, Weber M, Muller GA, Gross O. Prospective study on the potential of RAAS blockade to halt renal disease in Alport syndrome patients with heterozygous mutations. Pediatr Nephrol. 2017 Jan;32(1):131-137. doi: 10.1007/s00467-016-3452-z. Epub 2016 Jul 11.
PubMed 27402170Frese J, Kettwig M, Zappel H, Hofer J, Grone HJ, Nagel M, Sunder-Plassmann G, Kain R, Neuweiler J, Gross O. Kidney Injury by Variants in the COL4A5 Gene Aggravated by Polymorphisms in Slit Diaphragm Genes Causes Focal Segmental Glomerulosclerosis. Int J Mol Sci. 2019 Jan 26;20(3):519. doi: 10.3390/ijms20030519.
PubMed 30691124Boeckhaus J, Hoefele J, Riedhammer KM, Nagel M, Beck BB, Choi M, Gollasch M, Bergmann C, Sonntag JE, Troesch V, Stock J, Gross O. Lifelong effect of therapy in young patients with the COL4A5 Alport missense variant p.(Gly624Asp): a prospective cohort study. Nephrol Dial Transplant. 2022 Nov 23;37(12):2496-2504. doi: 10.1093/ndt/gfac006.
PubMed 35022790Zhang Y, Bockhaus J, Wang F, Wang S, Rubel D, Gross O, Ding J. Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome. Pediatr Nephrol. 2021 Sep;36(9):2719-2730. doi: 10.1007/s00467-021-05040-9. Epub 2021 Mar 27.
PubMed 33772369Boeckhaus J, Gross O. Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Hereditary Podocytopathies, Alport Syndrome, and FSGS: A Case Series to Better Plan a Large-Scale Study. Cells. 2021 Jul 18;10(7):1815. doi: 10.3390/cells10071815.
PubMed 34359984Boeckhaus J, Gale DP, Simon J, Ding J, Zhang Y, Bergmann C, Turner AN, Hall M, Sayer JA, Srivastava S, Kang HG, Cerkauskaite-Kerpauskiene A, Gillion V, Claes KJ, Krueger B, de Fallois J, Walden U, Choi M, Schueler M, Mueller RU, Todorova P, Hohenstein B, Zeisberg M, Friede T, Knebelmann B, Halbritter J, Gross O. SGLT2-Inhibition in Patients With Alport Syndrome. Kidney Int Rep. 2024 Sep 24;9(12):3490-3500. doi: 10.1016/j.ekir.2024.09.014. eCollection 2024 Dec.
PubMed 39698346
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- European Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome: Current and Novel Therapies
- ClinicalTrials.gov ID
- NCT02378805
- Acronym / sponsor ID
- Alport-XXL / Alport-UMG2010
- Conditions
- Alport Syndrome, Hereditary Kidney Disease, Pediatric Kidney Disease, Thin Basement Membrane Disease, Familial Benign Hematuria
- Keywords
- Alport syndrome, thin basement membrane disease, familial benign hematuria
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- University Hospital GoettingenUniversity, hospital or other
- Collaborators
- Society for Pediatric Nephrology (Germany)
- Study start
- Jul 1995
- Primary completion
- 1 Mar 2036 (estimated)
- Study completion
- 1 Mar 2036 (estimated)
- First posted
- 4 Mar 2015 (estimated)
- 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.
The hereditary type IV collagen disease Alport syndrome leads to kidney failure early in life. Currently there are no specific medications approved for treatment, however, several therapies have been evaluated preclinically and could improve outcome. For that reason, this non-interventional, observational study investigates, if medications (1) delay disease progression; (2) delay time to kidney failure; (3) improve life-expectancy compared to untreated patients (relatives). This observational study started in 2006 as an European registry. Since 2019, this registry has been expanded to "Alport XXL" via the International Alport Alliance as a global effort across all continents. From 2020 on to present, "Alport XXL" has a special focus on the outcomes of early therapy in young patients on ACE-inhibitors vs. Angiotensin-receptor blockers vs. their combination.
Detailed description
Early diagnosis in children with Alport syndrome (AS) with isolated hematuria opens a "window of opportunity" for early intervention. In the Alport mouse-model, this early intervention with the ACE-inhibitor Ramipril let to a delay of kidney failure by 111%. In order to observe treatment approaches for AS in humans, this registry has been established in 2006 to collect data over several generations of Alport families across Europe. In the meantime, this registry has been expanded to "Alport XXL" via the International Alport Alliance as a global effort across all continents.
Small children with AS first develop microscopic hematuria (stage 0), proceeding to microalbuminuria (stage I), overt proteinuria (stage II), impaired kidney function (stage III) and finally can end up with kidney failure (stage IV), leading to impaired quality of life and premature death (stage V). This registry uses these stages to assess if earlier initiation of medications such as ACE-inhibition at earlier stages of disease is more effective than later therapy in delaying the time to disease progression (doubeling or tripeling of albuminuria), delaying loss of estimated glomerular filtration rate (eGFR), and if therapy improves life-expectancy.
Untreated children with autosomal-recessive AS, digenic AS, and boys with X-linked AS typically all develop kidney failure early in life. Untreated girls with X-linked AS have a 30-40% risk of kidney failure, typically later in life (40 years or older). Untreated heterozygous patients with COL4A3/COL4A4 variants typically have a less severe phenotype (in former times also called "familial benign hematuria" or "thin basement membrane nephropathy" (TBMN)) and a 1-2% risk of kidney failure.
Several interim results of this registry have been published since 2012.
Alport XXL is designed and conducted as strictly observational, non-interventional data acquisition with prospective (and in parts retrospective) data analysis. Young patients with AS in disease stages 0,I,II from all over the world are included. The renewed version from 2021 has been re-approved by the Ethics Committee of the University Medical Center Göttingen as "Alport XXL", a further development of the former European Alport Therapy Registry (AZ 10/11/06). "Alport XXL" registry and data storage are in conformity with Good Clinical Practice guidelines.
ICH-GCP-conform patient information and data exchange is secured by data transfer and cooperation agreements between all international trial centers and the coordinating principal investigator at University Medical Center Goettingen. At baseline, data collection including retrospective data is performed using a standardized, ICH-GCP-conform and pseudonymized questionnaire assessing age, sex, weight, height, mode of inheritance (X-linked, autosomal, compound heterozygous/homozygous, number of missense variants), family history, albumin in 24-hour or spontaneous urine, serum-creatinine, RAS-blockade with preparation and dose. Follow-up visits include same data than baseline plus blood-pressure, smoking-status, serum-potassium, eGFR, hearing loss and eye involvement, other symptoms such as leiomyomatosis, comorbidities and adverse events (adverse events of special interest defined as hyperkalemia, cough, hypotension, acute renal failure, malignancy, death).
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Target follow-up
- 30 Years
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| no-T: untreated patients | – | –untreated patients, typically uncles or grandfathers of present patients. No Intervention (means no therapy until CKD stage V, on renal replacement therapy) |
| T-III: late therapy in patients | – | Drug: ACE-inhibitor, Drug: Angiotensin-receptor blocker (ARB), Drug: HMG-Coenzyme inhibitor (statin), Drug: Spironolactone or Finerenone, Drug: Paricalcitol, Drug: SGLT2 inhibitorpatients treated with medications with low eGFR (below 60 ml/min) (starts at patients with CKD stages III and IV). |
| T-II: early therapy in patients | – | Drug: ACE-inhibitor, Drug: Angiotensin-receptor blocker (ARB), Drug: HMG-Coenzyme inhibitor (statin), Drug: Spironolactone or Finerenone, Drug: Paricalcitol, Drug: SGLT2 inhibitortherapy starts in patients with albuminuria >300mg/gCreatinine and eGFR higher than 60 ml/min. |
| T-I: very early therapy in patients | – | Drug: ACE-inhibitor, Drug: Angiotensin-receptor blocker (ARB), Drug: HMG-Coenzyme inhibitor (statin), Drug: Spironolactone or Finerenone, Drug: Paricalcitol, Drug: SGLT2 inhibitortherapy starts in patients with microhematuria only (usually at birth) or microalbuminuria (30-300 mg albumin per gCreatinine). |
| no therapy in heterozygous patients | – | –heterozygous patients without therapy |
| therapy in heterozygous patients | – | Drug: ACE-inhibitor, Drug: Angiotensin-receptor blocker (ARB), Drug: HMG-Coenzyme inhibitor (statin), Drug: Spironolactone or Finerenone, Drug: Paricalcitol, Drug: SGLT2 inhibitorheterozygous patients with therapy (which also can be divided into subgroups stage T-0, I, II, III) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- For Alport XXL, eligible patients were children or young adults with a definitive diagnosis of AS by genetic analysis or kidney biopsy and at early stages of AS (stages 0, I or II) at baseline. AS stages were defined as: Stage 0 Microhematuria without microalbuminuria Stage I Microalbuminuria: UACR 30-300 mg/gCreatinine Stage II Proteinuria: UACR >300 with eGFR>60 ml/min/1.73m2 Stage III eGFR<60 ml/min/1.73m2 Stage IV end stage kidney failure Stage V death (from all causes)
Key inclusion criteria (2 listed)
- Diagnosis of Alport syndrome (AS) by kidney biopsy or mutation analysis (or both).
- Any type of genetic variant is accepted for X-linked, autosomal or digenic Alport syndrome (COL4A3, 4 or 5 genes).
Key exclusion criteria (1 listed)
- Patients not willing to give informed consent. Patient with suspected diagnosis, whcih cannot be confirmed.
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 |
|---|---|---|
| ACE-inhibitorobservational study | Drug | T-I: very early therapy in patients, T-II: early therapy in patients, T-III: late therapy in patients, therapy in heterozygous patients |
| Angiotensin-receptor blocker (ARB)observational study | Drug | T-I: very early therapy in patients, T-II: early therapy in patients, T-III: late therapy in patients, therapy in heterozygous patients |
| HMG-Coenzyme inhibitor (statin)observational study | Drug | T-I: very early therapy in patients, T-II: early therapy in patients, T-III: late therapy in patients, therapy in heterozygous patients |
| Spironolactone or Finerenoneobservational study | Drug | T-I: very early therapy in patients, T-II: early therapy in patients, T-III: late therapy in patients, therapy in heterozygous patients |
| Paricalcitolobservational study! | Drug | T-I: very early therapy in patients, T-II: early therapy in patients, T-III: late therapy in patients, therapy in heterozygous patients |
| SGLT2 inhibitorobservational study | Drug | T-I: very early therapy in patients, T-II: early therapy in patients, T-III: late therapy in patients, therapy in heterozygous patients |
Primary outcome
age at onset of end stage kidney failure (need for renal replacement therapy)
Time frame: until end of observation in 2037
kidney disease in Alport syndrome starts at birth, age at onset of end stage kidney failure in years
life-expectancy in years (age at death)
Time frame: until end of observation in 2037
Alport syndrome starts at birth, age at death of patients in years
yearly loss of estimated glomerular filtration rate (eGFR)
Time frame: until end of observation in 2037
kidney disease in Alport syndrome starts at birth, eGFR-loss per year in ml/min/1.73m2
time in years until doubling or tripling of urinary albumin to creatinine ratio (UACR)
Time frame: until end of observation in 2037
kidney disease in Alport syndrome starts at birth; time since birth to doubling (AS stages I or II) or tripling (AS stage 0) of UACR in years.
8 secondary outcomes
amount of albuminuria over time
Time frame: until end of observation in 2037
amount of proteinuria over time
Time frame: until end of observation in 2037
number of patients with X-chromosomal or autosomal inheritance
Time frame: until end of observation in 2037
number of patients experiencing side effects (AEs)
Time frame: until end of observation in 2037
number of patients with hearing loss
Time frame: until end of observation in 2037
number of patients with eye involvement
Time frame: until end of observation in 2037
number of patients with positive family history of end stage kidney failure
Time frame: until end of observation in 2037
age of relatives at end stage kidney failure
Time frame: until end of observation in 2037
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 6 Mar 2025.
- Background: PubMed 33159213Kashtan CE, Gross O. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol. 2021 Mar;36(3):711-719. doi: 10.1007/s00467-020-04819-6. Epub 2020 Nov 6.
- Background: PubMed 32386680Weinstock BA, Feldman DL, Fornoni A, Gross O, Kashtan CE, Lagas S, Lennon R, Miner JH, Rheault MN, Simon JF; Workshop Participants. Clinical trial recommendations for potential Alport syndrome therapies. Kidney Int. 2020 Jun;97(6):1109-1116. doi: 10.1016/j.kint.2020.02.029. Epub 2020 Apr 6.
- Results publication: PubMed 22997344Temme J, Kramer A, Jager KJ, Lange K, Peters F, Muller GA, Kramar R, Heaf JG, Finne P, Palsson R, Reisaeter AV, Hoitsma AJ, Metcalfe W, Postorino M, Zurriaga O, Santos JP, Ravani P, Jarraya F, Verrina E, Dekker FW, Gross O. Outcomes of male patients with Alport syndrome undergoing renal replacement therapy. Clin J Am Soc Nephrol. 2012 Dec;7(12):1969-76. doi: 10.2215/CJN.02190312. Epub 2012 Sep 20.
- Results publication: PubMed 22237748Temme J, Peters F, Lange K, Pirson Y, Heidet L, Torra R, Grunfeld JP, Weber M, Licht C, Muller GA, Gross O. Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations. Kidney Int. 2012 Apr;81(8):779-83. doi: 10.1038/ki.2011.452. Epub 2012 Jan 11.
- Results publication: PubMed 22166847Gross O, Licht C, Anders HJ, Hoppe B, Beck B, Tonshoff B, Hocker B, Wygoda S, Ehrich JH, Pape L, Konrad M, Rascher W, Dotsch J, Muller-Wiefel DE, Hoyer P; Study Group Members of the Gesellschaft fur Padiatrische Nephrologie; Knebelmann B, Pirson Y, Grunfeld JP, Niaudet P, Cochat P, Heidet L, Lebbah S, Torra R, Friede T, Lange K, Muller GA, Weber M. Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int. 2012 Mar;81(5):494-501. doi: 10.1038/ki.2011.407. Epub 2011 Dec 14.
- Results publication: PubMed 27402170Stock J, Kuenanz J, Glonke N, Sonntag J, Frese J, Tonshoff B, Hocker B, Hoppe B, Feldkotter M, Pape L, Lerch C, Wygoda S, Weber M, Muller GA, Gross O. Prospective study on the potential of RAAS blockade to halt renal disease in Alport syndrome patients with heterozygous mutations. Pediatr Nephrol. 2017 Jan;32(1):131-137. doi: 10.1007/s00467-016-3452-z. Epub 2016 Jul 11.
- Results publication: PubMed 30691124Frese J, Kettwig M, Zappel H, Hofer J, Grone HJ, Nagel M, Sunder-Plassmann G, Kain R, Neuweiler J, Gross O. Kidney Injury by Variants in the COL4A5 Gene Aggravated by Polymorphisms in Slit Diaphragm Genes Causes Focal Segmental Glomerulosclerosis. Int J Mol Sci. 2019 Jan 26;20(3):519. doi: 10.3390/ijms20030519.
- Results publication: PubMed 35022790Boeckhaus J, Hoefele J, Riedhammer KM, Nagel M, Beck BB, Choi M, Gollasch M, Bergmann C, Sonntag JE, Troesch V, Stock J, Gross O. Lifelong effect of therapy in young patients with the COL4A5 Alport missense variant p.(Gly624Asp): a prospective cohort study. Nephrol Dial Transplant. 2022 Nov 23;37(12):2496-2504. doi: 10.1093/ndt/gfac006.
- Results publication: PubMed 33772369Zhang Y, Bockhaus J, Wang F, Wang S, Rubel D, Gross O, Ding J. Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome. Pediatr Nephrol. 2021 Sep;36(9):2719-2730. doi: 10.1007/s00467-021-05040-9. Epub 2021 Mar 27.
- Results publication: PubMed 34359984Boeckhaus J, Gross O. Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Hereditary Podocytopathies, Alport Syndrome, and FSGS: A Case Series to Better Plan a Large-Scale Study. Cells. 2021 Jul 18;10(7):1815. doi: 10.3390/cells10071815.
- Results publication: PubMed 39698346Boeckhaus J, Gale DP, Simon J, Ding J, Zhang Y, Bergmann C, Turner AN, Hall M, Sayer JA, Srivastava S, Kang HG, Cerkauskaite-Kerpauskiene A, Gillion V, Claes KJ, Krueger B, de Fallois J, Walden U, Choi M, Schueler M, Mueller RU, Todorova P, Hohenstein B, Zeisberg M, Friede T, Knebelmann B, Halbritter J, Gross O. SGLT2-Inhibition in Patients With Alport Syndrome. Kidney Int Rep. 2024 Sep 24;9(12):3490-3500. doi: 10.1016/j.ekir.2024.09.014. eCollection 2024 Dec.
- Individual participant dataSharing planned: Undecided. Investigators plan to share the full data set with other researchers upon reasonable request via written cooperation agreements.
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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.
Oliver Gross, MD principal investigator
University Hospital Goettingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alport Syndrome and Hereditary Kidney Disease, run by University Hospital Goettingen at 1 site in Germany.
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 1 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 6 Mar 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 Germany. 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 Oliver Gross, MD (+49-551-39- ext. 60488, gross.oliver@med.uni-goettingen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
age at onset of end stage kidney failure (need for renal replacement therapy) (time frame: until end of observation in 2037). 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?
On the ClinicalTrials.gov record for NCT02378805, which also lists 11 linked publications.
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 6 Mar 2025.