Fabry DiseaseFORTIFYNCT06325488
Fibrosis, Inflammation, Oxygenation of Renal Tissue In FabrY Disease
An observational study of Fabry Disease and Chronic Kidney Diseases, run by Caroline Michaela Kistorp at 1 site in Denmark.
Trial summary
The overall objective of this study is to investigate Fabry-associated renal organ involvement by using a novel magnetic resonance imaging (MRI) approach, focusing on changes in renal oxygen levels by blood oxygenation-level dependent (BOLD) imaging. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Fabry Disease, Chronic Kidney Diseases
- How many people
- 60 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Jun 2024to 1 Jun 2026
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Participants with Fabry disease (n=40) - previously established by genetic testing - are to be grouped according to the presence of renal impairment as defined by the KDIGO criteria. A group of controls with no renal impairment are to act as healthy controls.
Who may be able to join
- Male and female individuals (≥18 years of age)
- Able to give informed consent
Who cannot join
- Any contraindication for magnetic resonance imaging according to standard checklist used in clinical routine, including claustrophobia or metallic foreign bodies, metallic implants, internal electrical devices, or permanent makeup/tattoos that cannot be declared MR compatible.
- Pregnancy
- Control group Inclusion criteria
- Male and female individuals (≥18 years of age)
- Able to give informed consent Exclusion criteria
- A genetically-verified diagnosis of Fabry disease.
Show all 13Show fewer
- Family member to a patient with a genetically-verified diagnosis of Fabry disease
- Cancer expected to influence life expectancy.
- Known heart failure, previous apoplexia or previously established kidney disease.
- Initiation or change of antihypertensive therapy within 3 months of enrolment
- Renal impairment as depicted by the CKD-EPI classification (≥ CKD G2/A1)
- Any contraindication for MRI according to standard checklist used in clinical routine, including claustrophobia or metallic foreign bodies, metallic implants, internal electrical devices, or permanent makeup/tattoos that cannot be declared MR compatible.
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Niels H Brandt-Jacobsen, MD, PhD contact
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet
Copenhagen, 2100
Caroline M Kistorp, MD, Ph.D, 004535459642, caroline.michaela.kistorp@regionh.dk
Niels H Brandt-Jacobsen, MD, Ph.D, 004538632412, niels.hoeeg.brandt-jacobsen.01@regionh.dk
About this study
The overall objective of this study is to investigate Fabry-associated renal organ involvement by using a novel magnetic resonance imaging (MRI) approach, focusing on changes in renal oxygen levels by blood oxygenation-level dependent (BOLD) imaging. Furthermore, to correlate renal oxygenation to the phenotypic presentation of patients with Fabry-associated nephropathy regarding circulating and imaging-derived biomarkers of kidney inflammation, fibrosis and injury as compared with healthy age- and sex-matched controls.
The study will achieve this by:
- Using a non-invasive, contrast-free MRI protocol focusing on parameters of oxygenation, inflammation, fibrosis, and injury in the kidney.
- Using an extensive, in-depth biomarker blood panel to investigate the pathological pathways associated with Fabry disease and Fabry-associated nephropathy.
Read the detailed description
From attached protocol:
Introduction Fabry disease is a rare X-linked lysosomal disorder caused by mutations in the gene encoding the enzyme alpha-galA, an essential enzyme for normal cellular function. The enzyme deficiency causes progressive accumulation of glycosphingolipids, especially globotriaosylceramide (Gb3) in virtually all organs, leading to dysfunction and eventually leading to organ failure. Although, Fabry disease is caused by an X-linked genetic mutation and the clinical implication among men with a classic phenotype are most severe, Fabry disease affects both males and females. Men with a non-classic phenotype and females present with a more heterogenous degree of organ involvement, however, these patients remain at increased risk of multisystem organ involvement and must be attend extensive screening, evaluated repeatedly in order to decide when and who are in need of treatment. However, as evident in patients with the several known genotypes, which presents with no or very low alpha-galA-activity and develop early multi-organ involvement, one of the complication of greatest prognostic impact is an early involvement of the kidney.
Fabry nephropathy Although, the etiology of kidney affection in Fabry disease in general is well established, the actual mechanisms of progression - and thus the targets of therapeutic approach - are largely unknown. Fabry nephropathy is characterized by the accumulation of Gb3 deposition in podocytes, epithelial cells and endothelial cells throughout the tubules, where kidney biopsies suggest healthy, functioning tissue is substituted with reparative diffuse fibrosis. Indeed, evidence shows a direct association between Gb3 accumulation and both a decline in renal glomerular filtration rate and an increase in urinary albumin excretion - both clinically validated biomarkers of kidney injury and decline in function. Given Gb3 accumulation in Fabry disease accounts for less than 5% of the total tissue volume at maximum, the disproportionate and devastating effects observed have led to the proposal of Gb3 having additional effects beyond mere storage. Oxidative stress, endothelial dysfunction, and inflammation have been proposed as important mechanisms induced directly or indirectly by Gb3 accumulation, resulting in increased cell-death of functioning glomeruli with unamenable, reparative fibrosis as a result. Furthermore, certain cells seems more susceptible to injury and less susceptible to the benefits expected from Fabry-specific treatment; an important example being renal podocytes.
Fabry nephropathy and Magnetic Resonance Imaging Renal hypoxia is now considered to play a key role in the development of chronic kidney disease (CKD). Using a novel contrast-free, non-invasive magnetic resonance imaging (MRI), our collaborative partners have reported renal hypoxia in subjects with type I diabetes and pathological urinary albumin/creatinine ratio (UACR) levels. Recent advances in MRI thus, enables us to investigate the pathological mechanisms underlining Fabry nephropathy by non-invasively measurements of oxygenation, inflammation and fibrosis. The kidney's oxidative capacity evaluated by R2*-related blood oxygenation level-dependent (BOLD) MRI has been validated as a parameter of renal cortical and medullar oxygen-partial pressure. Furthermore, changes in dynamic R2*-signaling have been validated as a non-invasive, contrast-free measure of renal oxygenation capacity, which becomes reduced with presence of chronic kidney disease. Concurrently, arterial spin labelling (ASL) is able to provide a reliable measure of total blood flow as well as regional blood flow in the renal artery and the kidney. Finally, the inflammatory and fibrotic burden can be elucidated upon by diffusion-weighted sequences and native T1-mapping. Therefore, this novel method provides information on kidney-specific shift in energetic oxygen-dependent capacity, ongoing inflammation, and accumulation of fibrosis, with changes not only portraying key aspects of kidney physiology, but changes expected to elucidate on the pathophysiology forming the very basis of Fabry nephropathy.
While the recent advances in imaging present a unique possibility for early detection of Fabry nephropathy, there is a need for validation against clinically established biomarkers of risk such as pathologically increased UACR - currently the greatest predictor of progressive loss of glomerular function in regards to end-stage renal disease in general and in Fabry nephropathy. Pathological UACR levels is considered the first clinical sign of Fabry nephropathy, with an estimated prevalence of 50% among men aged 35 years. Even among women, which often less severely afflicted, up to 40% develop proteinuria and 15% experience a clinically significant renal event, thus, the prognostic importance of increased UACR in Fabry disease is evident. Therefore, UACR levels is the key clinical parameter of Fabry nephropathy as recommended in guidelines.
- Conditions
- Fabry Disease, Chronic Kidney Diseases
- Keywords
- Oxygenation, Inflammation, Fibrosis
- Medical subject headings
- Fabry Disease, Renal Insufficiency, Chronic, Inflammation, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with Fabry Disease and impaired kidney function | Participants included in this group * 18 years of age or above * Fabry Disease as verified by genetic analysis prior to inclusion * Impaired kidney function according to the KDIGO classification (UACR ≥ 30 mg/g and eGFR < 60 ml/min/1.73m2 [≥ CKD G3a/A2]) | |
| Patients with Fabry Disease and normal kidney function | Participants included in this group * 18 years of age or above * Fabry Disease as verified by genetic analysis prior to inclusion * Normal kidney function according to the KDIGO classification (UACR < 30 mg/g and eGFR ≥ 60 will be included [≤ CKD G2/A1]) | |
| Healthy controls | Participants included in this group * 18 years of age or above * Normal kidney function according to the KDIGO classification (UACR < 30 mg/g and eGFR ≥ 60 will be included [≤ CKD G2/A1]) Furthermore, healthy controls are excluded * Suspected of Fabry Disease or verified by genetic analysis * Related to a patient with Fabry Disease * Have cancer with an expected influence on life expectancy * Known apoplexia cerebri, heart failure or established kidney disease * Recently initiated or have had recent changes in antihypertensive medication (within 3 months) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal hypoxia (Fabry patients according to renal impairment)
A between-group difference in renal hypoxia (R*) evaluated by BOLD MRI when comparing the groups of patients with Fabry disease.
Measured: At baseline
Secondary outcomes (5)
Renal hypoxia (Fabry patient vs controls)
A between-group difference in renal hypoxia (R*) evaluated by BOLD MRI when comparing patients with Fabry disease irrespective of renal impairment with the control group.
Measured: At baseline
Renal cortical perfusion (Fabry vs. controls)
A between-group difference in perfusion of the renal medulla (mL/100g/min) when comparing groups with Fabry disease patients with the control group
Measured: At baseline
Renal medullar perfusion (Fabry vs. controls)
A between-group difference in renal blood flow (mL/min) when comparing groups with Fabry disease patients with the control group.
Measured: At baseline
Renal inflammation (Fabry vs. controls)
A between-group difference in native T1 (ms) when comparing groups with Fabry disease patients with the control group.
Measured: At baseline
Renal fibrosis (Fabry vs. controls)
A between-group difference in diffusion-weigthed signaling when comparing groups with Fabry disease patients with the control group.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2024
- Study start1 Jun 2024
- Primary completion1 Mar 2026 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Caroline Michaela Kistorp
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor-investigator, Caroline Michaela Kistorp, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Caroline M Kistorp, Professor, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06325488
- Sponsor's protocol ID
- H-23035668
- Acronym
- FORTIFY
- Status last verified
- Apr 2025
- First submitted
- 14 Feb 2024
- Last updated
- 6 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Due to national legistlative restrictions, unrestricted access to individual participant data is not possible. However, data exchange will be possible upon reasonable request under the assurance of data-management in accordance with Danish law.
Publications
Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P. Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genet Med. 2009 Nov;11(11):790-6. doi: 10.1097/GIM.0b013e3181bb05bb.
PubMed 19745746Wanner C, Germain DP, Hilz MJ, Spada M, Falissard B, Elliott PM. Therapeutic goals in Fabry disease: Recommendations of a European expert panel, based on current clinical evidence with enzyme replacement therapy. Mol Genet Metab. 2019 Mar;126(3):210-211. doi: 10.1016/j.ymgme.2018.04.004. Epub 2018 Apr 11. No abstract available.
PubMed 29724657Najafian B, Tondel C, Svarstad E, Gubler MC, Oliveira JP, Mauer M. Accumulation of Globotriaosylceramide in Podocytes in Fabry Nephropathy Is Associated with Progressive Podocyte Loss. J Am Soc Nephrol. 2020 Apr;31(4):865-875. doi: 10.1681/ASN.2019050497. Epub 2020 Mar 3.
PubMed 32127409Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D, Feldt-Rasmussen U, Nedd K, Sharaf El Din U, Lourenco CM, Banikazemi M, Charrow J, Dasouki M, Finegold D, Giraldo P, Goker-Alpan O, Longo N, Scott CR, Torra R, Tuffaha A, Jovanovic A, Waldek S, Packman S, Ludington E, Viereck C, Kirk J, Yu J, Benjamin ER, Johnson F, Lockhart DJ, Skuban N, Castelli J, Barth J, Barlow C, Schiffmann R. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016 Aug 11;375(6):545-55. doi: 10.1056/NEJMoa1510198.
PubMed 27509102Jehn U, Bayraktar S, Pollmann S, Van Marck V, Weide T, Pavenstadt H, Brand E, Lenders M. alpha-Galactosidase a Deficiency in Fabry Disease Leads to Extensive Dysregulated Cellular Signaling Pathways in Human Podocytes. Int J Mol Sci. 2021 Oct 20;22(21):11339. doi: 10.3390/ijms222111339.
PubMed 34768768Linhart A, Elliott PM. The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart. 2007 Apr;93(4):528-35. doi: 10.1136/hrt.2005.063818. No abstract available.
PubMed 17401074Yogasundaram H, Kim D, Oudit O, Thompson RB, Weidemann F, Oudit GY. Clinical Features, Diagnosis, and Management of Patients With Anderson-Fabry Cardiomyopathy. Can J Cardiol. 2017 Jul;33(7):883-897. doi: 10.1016/j.cjca.2017.04.015. Epub 2017 May 4.
PubMed 28668140Eikrem O, Skrunes R, Tondel C, Leh S, Houge G, Svarstad E, Marti HP. Pathomechanisms of renal Fabry disease. Cell Tissue Res. 2017 Jul;369(1):53-62. doi: 10.1007/s00441-017-2609-9. Epub 2017 Apr 12. No abstract available.
PubMed 28401309Ravarotto V, Simioni F, Carraro G, Bertoldi G, Pagnin E, Calo LA. Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? J Clin Med. 2018 Nov 2;7(11):409. doi: 10.3390/jcm7110409.
PubMed 30400144Sanchez-Nino MD, Carpio D, Sanz AB, Ruiz-Ortega M, Mezzano S, Ortiz A. Lyso-Gb3 activates Notch1 in human podocytes. Hum Mol Genet. 2015 Oct 15;24(20):5720-32. doi: 10.1093/hmg/ddv291. Epub 2015 Jul 23.
PubMed 26206887Ravarotto V, Carraro G, Pagnin E, Bertoldi G, Simioni F, Maiolino G, Martinato M, Landini L, Davis PA, Calo LA. Oxidative stress and the altered reaction to it in Fabry disease: A possible target for cardiovascular-renal remodeling? PLoS One. 2018 Sep 27;13(9):e0204618. doi: 10.1371/journal.pone.0204618. eCollection 2018.
PubMed 30261035Fall B, Scott CR, Mauer M, Shankland S, Pippin J, Jefferson JA, Wallace E, Warnock D, Najafian B. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy. PLoS One. 2016 Dec 16;11(12):e0168346. doi: 10.1371/journal.pone.0168346. eCollection 2016.
PubMed 27992580Selby NM, Blankestijn PJ, Boor P, Combe C, Eckardt KU, Eikefjord E, Garcia-Fernandez N, Golay X, Gordon I, Grenier N, Hockings PD, Jensen JD, Joles JA, Kalra PA, Kramer BK, Mark PB, Mendichovszky IA, Nikolic O, Odudu A, Ong ACM, Ortiz A, Pruijm M, Remuzzi G, Rorvik J, de Seigneux S, Simms RJ, Slatinska J, Summers P, Taal MW, Thoeny HC, Vallee JP, Wolf M, Caroli A, Sourbron S. Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA. Nephrol Dial Transplant. 2018 Sep 1;33(suppl_2):ii4-ii14. doi: 10.1093/ndt/gfy152.
PubMed 30137584Pruijm M, Milani B, Burnier M. Blood Oxygenation Level-Dependent MRI to Assess Renal Oxygenation in Renal Diseases: Progresses and Challenges. Front Physiol. 2017 Jan 5;7:667. doi: 10.3389/fphys.2016.00667. eCollection 2016.
PubMed 28105019Heyman SN, Khamaisi M, Rosen S, Rosenberger C. Renal parenchymal hypoxia, hypoxia response and the progression of chronic kidney disease. Am J Nephrol. 2008;28(6):998-1006. doi: 10.1159/000146075. Epub 2008 Jul 18.
PubMed 18635927
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibrosis, Inflammation, Oxygenation of Renal Tissue In FabrY Disease
- ClinicalTrials.gov ID
- NCT06325488
- Acronym / sponsor ID
- FORTIFY / H-23035668
- Conditions
- Fabry Disease, Chronic Kidney Diseases
- Keywords
- Oxygenation, Inflammation, Fibrosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Caroline Michaela KistorpUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 1 Mar 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 22 Mar 2024 (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.
The overall objective of this study is to investigate Fabry-associated renal organ involvement by using a novel magnetic resonance imaging (MRI) approach, focusing on changes in renal oxygen levels by blood oxygenation-level dependent (BOLD) imaging. Furthermore, to correlate renal oxygenation to the phenotypic presentation of patients with Fabry-associated nephropathy regarding circulating and imaging-derived biomarkers of kidney inflammation, fibrosis and injury as compared with healthy age- and sex-matched controls.
The study will achieve this by:
- Using a non-invasive, contrast-free MRI protocol focusing on parameters of oxygenation, inflammation, fibrosis, and injury in the kidney.
- Using an extensive, in-depth biomarker blood panel to investigate the pathological pathways associated with Fabry disease and Fabry-associated nephropathy.
Detailed description
From attached protocol:
Introduction Fabry disease is a rare X-linked lysosomal disorder caused by mutations in the gene encoding the enzyme alpha-galA, an essential enzyme for normal cellular function. The enzyme deficiency causes progressive accumulation of glycosphingolipids, especially globotriaosylceramide (Gb3) in virtually all organs, leading to dysfunction and eventually leading to organ failure. Although, Fabry disease is caused by an X-linked genetic mutation and the clinical implication among men with a classic phenotype are most severe, Fabry disease affects both males and females. Men with a non-classic phenotype and females present with a more heterogenous degree of organ involvement, however, these patients remain at increased risk of multisystem organ involvement and must be attend extensive screening, evaluated repeatedly in order to decide when and who are in need of treatment. However, as evident in patients with the several known genotypes, which presents with no or very low alpha-galA-activity and develop early multi-organ involvement, one of the complication of greatest prognostic impact is an early involvement of the kidney.
Fabry nephropathy Although, the etiology of kidney affection in Fabry disease in general is well established, the actual mechanisms of progression - and thus the targets of therapeutic approach - are largely unknown. Fabry nephropathy is characterized by the accumulation of Gb3 deposition in podocytes, epithelial cells and endothelial cells throughout the tubules, where kidney biopsies suggest healthy, functioning tissue is substituted with reparative diffuse fibrosis. Indeed, evidence shows a direct association between Gb3 accumulation and both a decline in renal glomerular filtration rate and an increase in urinary albumin excretion - both clinically validated biomarkers of kidney injury and decline in function. Given Gb3 accumulation in Fabry disease accounts for less than 5% of the total tissue volume at maximum, the disproportionate and devastating effects observed have led to the proposal of Gb3 having additional effects beyond mere storage. Oxidative stress, endothelial dysfunction, and inflammation have been proposed as important mechanisms induced directly or indirectly by Gb3 accumulation, resulting in increased cell-death of functioning glomeruli with unamenable, reparative fibrosis as a result. Furthermore, certain cells seems more susceptible to injury and less susceptible to the benefits expected from Fabry-specific treatment; an important example being renal podocytes.
Fabry nephropathy and Magnetic Resonance Imaging Renal hypoxia is now considered to play a key role in the development of chronic kidney disease (CKD). Using a novel contrast-free, non-invasive magnetic resonance imaging (MRI), our collaborative partners have reported renal hypoxia in subjects with type I diabetes and pathological urinary albumin/creatinine ratio (UACR) levels. Recent advances in MRI thus, enables us to investigate the pathological mechanisms underlining Fabry nephropathy by non-invasively measurements of oxygenation, inflammation and fibrosis. The kidney's oxidative capacity evaluated by R2*-related blood oxygenation level-dependent (BOLD) MRI has been validated as a parameter of renal cortical and medullar oxygen-partial pressure. Furthermore, changes in dynamic R2*-signaling have been validated as a non-invasive, contrast-free measure of renal oxygenation capacity, which becomes reduced with presence of chronic kidney disease. Concurrently, arterial spin labelling (ASL) is able to provide a reliable measure of total blood flow as well as regional blood flow in the renal artery and the kidney. Finally, the inflammatory and fibrotic burden can be elucidated upon by diffusion-weighted sequences and native T1-mapping. Therefore, this novel method provides information on kidney-specific shift in energetic oxygen-dependent capacity, ongoing inflammation, and accumulation of fibrosis, with changes not only portraying key aspects of kidney physiology, but changes expected to elucidate on the pathophysiology forming the very basis of Fabry nephropathy.
While the recent advances in imaging present a unique possibility for early detection of Fabry nephropathy, there is a need for validation against clinically established biomarkers of risk such as pathologically increased UACR - currently the greatest predictor of progressive loss of glomerular function in regards to end-stage renal disease in general and in Fabry nephropathy. Pathological UACR levels is considered the first clinical sign of Fabry nephropathy, with an estimated prevalence of 50% among men aged 35 years. Even among women, which often less severely afflicted, up to 40% develop proteinuria and 15% experience a clinically significant renal event, thus, the prognostic importance of increased UACR in Fabry disease is evident. Therefore, UACR levels is the key clinical parameter of Fabry nephropathy as recommended in guidelines.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients with Fabry Disease and impaired kidney function | – | –Participants included in this group * 18 years of age or above * Fabry Disease as verified by genetic analysis prior to inclusion * Impaired kidney function according to the KDIGO classification (UACR ≥ 30 mg/g and eGFR < 60 ml/min/1.73m2 [≥ CKD G3a/A2]) |
| Patients with Fabry Disease and normal kidney function | – | –Participants included in this group * 18 years of age or above * Fabry Disease as verified by genetic analysis prior to inclusion * Normal kidney function according to the KDIGO classification (UACR < 30 mg/g and eGFR ≥ 60 will be included [≤ CKD G2/A1]) |
| Healthy controls | – | –Participants included in this group * 18 years of age or above * Normal kidney function according to the KDIGO classification (UACR < 30 mg/g and eGFR ≥ 60 will be included [≤ CKD G2/A1]) Furthermore, healthy controls are excluded * Suspected of Fabry Disease or verified by genetic analysis * Related to a patient with Fabry Disease * Have cancer with an expected influence on life expectancy * Known apoplexia cerebri, heart failure or established kidney disease * Recently initiated or have had recent changes in antihypertensive medication (within 3 months) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Participants with Fabry disease (n=40) - previously established by genetic testing - are to be grouped according to the presence of renal impairment as defined by the KDIGO criteria. A group of controls with no renal impairment are to act as healthy controls.
Key inclusion criteria (2 listed)
- Male and female individuals (≥18 years of age)
- Able to give informed consent
Key exclusion criteria (13 listed)
- Any contraindication for magnetic resonance imaging according to standard checklist used in clinical routine, including claustrophobia or metallic foreign bodies, metallic implants, internal electrical devices, or permanent makeup/tattoos that cannot be declared MR compatible.
- Pregnancy
- Control group Inclusion criteria
- Male and female individuals (≥18 years of age)
- Able to give informed consent Exclusion criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Renal hypoxia (Fabry patients according to renal impairment)
Time frame: At baseline
A between-group difference in renal hypoxia (R*) evaluated by BOLD MRI when comparing the groups of patients with Fabry disease.
5 secondary outcomes
Renal hypoxia (Fabry patient vs controls)
Time frame: At baseline
Renal cortical perfusion (Fabry vs. controls)
Time frame: At baseline
Renal medullar perfusion (Fabry vs. controls)
Time frame: At baseline
Renal inflammation (Fabry vs. controls)
Time frame: At baseline
Renal fibrosis (Fabry vs. controls)
Time frame: At baseline
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 Apr 2025.
- Background: PubMed 19745746Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P. Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genet Med. 2009 Nov;11(11):790-6. doi: 10.1097/GIM.0b013e3181bb05bb.
- Background: PubMed 29724657Wanner C, Germain DP, Hilz MJ, Spada M, Falissard B, Elliott PM. Therapeutic goals in Fabry disease: Recommendations of a European expert panel, based on current clinical evidence with enzyme replacement therapy. Mol Genet Metab. 2019 Mar;126(3):210-211. doi: 10.1016/j.ymgme.2018.04.004. Epub 2018 Apr 11. No abstract available.
- Background: PubMed 32127409Najafian B, Tondel C, Svarstad E, Gubler MC, Oliveira JP, Mauer M. Accumulation of Globotriaosylceramide in Podocytes in Fabry Nephropathy Is Associated with Progressive Podocyte Loss. J Am Soc Nephrol. 2020 Apr;31(4):865-875. doi: 10.1681/ASN.2019050497. Epub 2020 Mar 3.
- Background: PubMed 27509102Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D, Feldt-Rasmussen U, Nedd K, Sharaf El Din U, Lourenco CM, Banikazemi M, Charrow J, Dasouki M, Finegold D, Giraldo P, Goker-Alpan O, Longo N, Scott CR, Torra R, Tuffaha A, Jovanovic A, Waldek S, Packman S, Ludington E, Viereck C, Kirk J, Yu J, Benjamin ER, Johnson F, Lockhart DJ, Skuban N, Castelli J, Barth J, Barlow C, Schiffmann R. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016 Aug 11;375(6):545-55. doi: 10.1056/NEJMoa1510198.
- Background: PubMed 34768768Jehn U, Bayraktar S, Pollmann S, Van Marck V, Weide T, Pavenstadt H, Brand E, Lenders M. alpha-Galactosidase a Deficiency in Fabry Disease Leads to Extensive Dysregulated Cellular Signaling Pathways in Human Podocytes. Int J Mol Sci. 2021 Oct 20;22(21):11339. doi: 10.3390/ijms222111339.
- Background: PubMed 17401074Linhart A, Elliott PM. The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart. 2007 Apr;93(4):528-35. doi: 10.1136/hrt.2005.063818. No abstract available.
- Background: PubMed 28668140Yogasundaram H, Kim D, Oudit O, Thompson RB, Weidemann F, Oudit GY. Clinical Features, Diagnosis, and Management of Patients With Anderson-Fabry Cardiomyopathy. Can J Cardiol. 2017 Jul;33(7):883-897. doi: 10.1016/j.cjca.2017.04.015. Epub 2017 May 4.
- Background: PubMed 28401309Eikrem O, Skrunes R, Tondel C, Leh S, Houge G, Svarstad E, Marti HP. Pathomechanisms of renal Fabry disease. Cell Tissue Res. 2017 Jul;369(1):53-62. doi: 10.1007/s00441-017-2609-9. Epub 2017 Apr 12. No abstract available.
- Background: PubMed 30400144Ravarotto V, Simioni F, Carraro G, Bertoldi G, Pagnin E, Calo LA. Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? J Clin Med. 2018 Nov 2;7(11):409. doi: 10.3390/jcm7110409.
- Background: PubMed 26206887Sanchez-Nino MD, Carpio D, Sanz AB, Ruiz-Ortega M, Mezzano S, Ortiz A. Lyso-Gb3 activates Notch1 in human podocytes. Hum Mol Genet. 2015 Oct 15;24(20):5720-32. doi: 10.1093/hmg/ddv291. Epub 2015 Jul 23.
- Background: PubMed 30261035Ravarotto V, Carraro G, Pagnin E, Bertoldi G, Simioni F, Maiolino G, Martinato M, Landini L, Davis PA, Calo LA. Oxidative stress and the altered reaction to it in Fabry disease: A possible target for cardiovascular-renal remodeling? PLoS One. 2018 Sep 27;13(9):e0204618. doi: 10.1371/journal.pone.0204618. eCollection 2018.
- Background: PubMed 27992580Fall B, Scott CR, Mauer M, Shankland S, Pippin J, Jefferson JA, Wallace E, Warnock D, Najafian B. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy. PLoS One. 2016 Dec 16;11(12):e0168346. doi: 10.1371/journal.pone.0168346. eCollection 2016.
- Individual participant dataSharing planned: No. Due to national legistlative restrictions, unrestricted access to individual participant data is not possible. However, data exchange will be possible upon reasonable request under the assurance of data-management in accordance with Danish law.
Related trials for Fabry Disease
RecruitingPhase 3
A Study to Learn How Well Lucerastat Works and How Safe it is in Untreated Adult Male Participants With Fabry Disease
Fabry Disease
RecruitingObservational study
A Study of Patients With Fabry Disease (US Specific)
Fabry Disease
RecruitingObservational study
A Global Prospective Observational Study of Women With Fabry Disease and Their Infants During Pregnancy and Breastfeeding
Fabry Disease
Active, not recruiting
Evaluation of the Effect of a Low-FODMAP Diet on Gastrointestinal Symptoms and Inflammatory Markers in Fabry Patients
Fabry Disease
RecruitingPhase 3
A Study of Migalastat in Pediatric Subjects (2 to <12 Yrs) With Fabry Disease and Amenable GLA Variants
Fabry Disease
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.
Niels H Brandt-Jacobsen, MD, PhD contact
Caroline M Kistorp, Professor principal investigator
Copenhagen University Hospital, Rigshospitalet
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 Fabry Disease and Chronic Kidney Diseases, run by Caroline Michaela Kistorp at 1 site in Denmark.
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 13 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 Apr 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 Denmark. 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 Caroline M Kistorp, Professor (35 45 96 42 ext. 0045, caroline.michaela.kistorp@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Renal hypoxia (Fabry patients according to renal impairment) (time frame: At baseline). 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 NCT06325488, which also lists 22 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 Apr 2025.