Diabetes ComplicationsPhase 2FOXTROTNCT05810311
The Effect of Roxadustat on Renal Oxygenation in Diabetes Nephropathy
A Phase 2 study testing Roxadustat and Darbepoietin Alfa in people with Diabetes Complications and Diabetes; Nephropathy (Manifestation), run by Region Stockholm at 1 site in Sweden.
Trial summary
The study will investigate if treatment with Roxadustat improves kidney oxygenation in diabetic patients with nephropathy receiving treatment for renal anemia, compared to patients receiving treatment with darbepoetin alpha. Participants will be randomized to either treatment, and receive equal care for renal anemia. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetes Complications, Diabetes; Nephropathy (Manifestation)
- What is being tested?
- Roxadustat and Darbepoietin Alfa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSweden
- Study dates
- 1 Jun 2025to 31 Dec 2027
- Phase
- Phase 2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diabetes mellitus with anemia caused by DKD, and indication for treatment with erythropoetin/erythropoietin-stimulating drugs.
- Age 18-75
- HbA1c >55
- Diabetes duration 10+ years.
- Chronic kidney disease (CKD) stage 3-4
- Symptomatic anemia with Hb <10g/dl
Show all 13Show fewer
- Contraception: Female subjects must be postmenopausal, surgically sterile, or if premenopausal (and not surgically sterile), be prepared to use ≥1 effective method of contraception during the study and for 30 days after the last visit. Effective methods of contraception are those listed below:
- Double barrier method, i.e. (a) condom (male or female) or (b) diaphragm, with spermicide; or
- Intrauterine device; or
- Vasectomy (partner); or
- Hormonal (e.g., contraceptive pill, patch, intramuscular implant, or injection); or
- Abstinence, if in line with the preferred and usual lifestyle of the subject.
- Signed informed consent.
Who cannot join
- Anemia not related to CKD.
- Dialysis dependent CKD
- Currently treated for renal anemia using erythropoietin-stimulating drugs
- Infections during the last 30 days.
- Severe hypertension (≥180mmHg systolic or >110mmHg diastolic blood pressure)
- Liver failure (Child-Pugh class B-C)
Show all 17Show fewer
- History of epilepsy or seizures
- Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.
- Ongoing drug or alcohol abuse.
- Known allergy to RD or DA
- Malignancy
- Severe claustrophobia
- Participation in another ongoing pharmacological study
- If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or currently breastfeeding.
- Unwillingness to participate following oral and written information
- Other severe acute or chronic medical or psychiatric condition that makes the subject inappropriate for the study, as judged by the investigator.
- History of thrombosis (DVT, pulmonary embolism)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Andris Elksnis, PhD contact
Sweden1 site
Centre for diabetes
Stockholm
Sergiu Catrina, Ass. Prof., sergiu.catrina@ki.se
Sergiu Catrina, Ass. Prof.
About this study
Official title: The Effect of Roxadustat on the Levels of Renal Oxygenation in Patients With Diabetes Nephropathy (FOXTROT)
The study will investigate if treatment with Roxadustat improves kidney oxygenation in diabetic patients with nephropathy receiving treatment for renal anemia, compared to patients receiving treatment with darbepoetin alpha.
Participants will be randomized to either treatment, and receive equal care for renal anemia. Kidney oxygenation will be examined before treatment start and after 24 weeks using BOLD-MRI (blood oxygen level-defendant MRI), a non-invasive method available for measurement of tissue oxygenation levels that is comparable with direct invasive measurement of partial oxygen pressure. Blood and urin samples will be collected in connection to these visits. The primary endpoint is the change in medullary and cortical R2* (inversely proportional to the tissue oxygenation content) after 24 weeks. Secondary endpoints will be albuminuria and urinary levels of ROS (evaluated by electron paramagnetic resonance (EPR) spectroscopy with CPH spin probes).
Read the detailed description
Aims
The general aim of this study is to investigate the effects of systemic administration of Evrenzo (Roxadustat [RD]) or Aranesp (darbepoetin alpha [DA]) on the levels of renal oxygenation in patients with diabetic nephropathy and associated anemia.
The investigation will elucidate if RD, a prolyl-hydroxylase (PHD) inhibitor and subsequent Hypoxia-Inducible Factor 1 (HIF) activator, can reduce renal hypoxia, compared to DA, which lacks effects on HIF.
Background
Diabetes complications represent a huge health problem and concern for modern diabetes therapy, with dramatic consequences for the affected individuals and society.
Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and accounts for a high morbidity and mortality rate in patients with diabetes. Today, the treatment for DKD focuses on optimizing the patients' metabolic control, blood lipid levels and blood pressure, which unfortunately is optimally achieved in just a restricted portion of patients (1). Thus, there is a great need of identifying novel therapies that could improve or prevent progression DKD.
While hyperglycemia is the major factor contributing to the development of diabetes complications, the role of hypoxia has recently become increasingly evident as another central factor in all diabetes complications (2). Several effects may contribute to the development of hypoxia in diabetes, including deficient blood supply secondary to micro- and macro-vascular disease, poor local oxygen diffusion secondary to local oedema, or as a result of increased oxygen consumption (3, 4, 5, 6).
HIF-1, a heterodimeric transcription factor, is a central regulator of cellular adaptive response to hypoxia (7). HIF consists of two subunits (alpha and beta), both constitutively expressed in mammalian cells. In normoxia, HIF-1alpha is continuously degraded by the ubiquitin-proteasome system because of the oxygen-dependent hydroxylation of two key proline residues catalyzed by a group of enzymes known as prolyl-hydroxylases (PHDs) (7). Upon hypoxia, this degradation pathway is suppressed and HIF-1alpha is stabilized, translocates to the nucleus where it dimerizes with HIF-1beta and induces the expression of more than 800 genes involved in angiogenesis, glycolytic energy metabolism, proliferation and survival that enables the cells to adapt to reduced oxygen availability (8, 9). HIF-1 is central for expression of several angiogenic growth factors (e.g., VEGF, erythropoietin (EPO), stromal cell-derived factor-1alpha) (10).
Lately, accumulating evidence points to a defective cellular response to hypoxia in diabetes. This defective hypoxia response has been shown to be present in all tissues that develop complications in both animal models for diabetes and in patients with diabetes as a consequence of impaired HIF signaling, and there is a direct suppressive effect of hyperglycemia on HIF function (11). Studies in animal models of diabetes have demonstrated that restoring HIF function in hyperglycemia can prevent the development of multiple diabetes complications, including DKD (7).
RD is a PHD inhibitor that stabilizes HIF-1 by preventing PHD dependent degradation of HIF-1alpha, and has recently been approved for treatment of renal anemia. As hypoxia plays a central pathogenic role even in the early stages of DKD (12), and activation of HIF signaling has recently been demonstrated to have protective effects in animal models of DKD (13), it is of great interest to also investigate the potential role of RD as a targeted therapy for DKD in humans.
The presently proposed project aims to investigate the potential of RD to improve renal oxygenation in patients with DKD and anemia, compared to DA which lacks the above-mentioned effects on HIF and is an alternative treatment for the same condition. To examine this the investigators plan to use BOLD-MRI (blood oxygen level-defendant MRI), a non-invasive method available for measurement of tissue oxygenation levels that is comparable with direct invasive measurement of partial oxygen pressure (14).
Research design
The research design is a randomized prospective, open-label study with parallel groups of 15 participants/group with non-dialysis dependent DKD CKD stage 3-4 with Hb <10g/dl (the level of Hb recommended for RD/DA treatment). One group will receive Roxadustat (Evrenzo) three times weekly at an initial dose of 70mg (for body weight <100.0 kg) or 100 mg (for body weight weight ≥100.0 kg). The control group will receive darbepoietin alpha (Aranesp) s.c. 0.45mg/kg once a week. The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl.
Kidney oxygenation will be evaluated using BOLD-MRI prior to start of therapy, and once again after 24 weeks of treatment with either RD or DA. Primary endpoint is the change in medullary and cortical R2* (inversely proportional to the tissue oxygenation content) after 24 weeks. Secondary endpoints will be albuminuria and urinary levels of ROS (evaluated by electron paramagnetic resonance (EPR) spectroscopy with CPH spin probes).
- Being tested
- Roxadustat, Darbepoietin Alfa
- Keywords
- HIF, Hypoxia, Diabetes mellitus, Nephropathy, BOLD-MRI, Kidney oxygenation
- Medical subject headings
- Diabetes Complications, Diabetes Mellitus, Kidney Diseases, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RoxadustatDrug
Also called Evrenzo
The group will receive Roxadustat (Evrenzo) three times weekly at an initial dose of 70mg (for body weight <100.0 kg) or 100 mg (for body weight weight ≥100.0 kg). The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl.
The aim is to investigate the effects of systemic administration of Evrenzo (Roxadustat [RD]) or Aranesp (darbepoetin alpha [DA]) on the levels of renal oxygenation in patients with diabetic nephropathy and associated anemia.
Darbepoietin AlfaDrug
Also called Aranesp
The control group will receive darbepoietin alpha (Aranesp) s.c. 0.45mg/kg once a week. The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl.
The aim is to investigate the effects of systemic administration of Evrenzo (Roxadustat [RD]) or Aranesp (darbepoetin alpha [DA]) on the levels of renal oxygenation in patients with diabetic nephropathy and associated anemia.
| Study group | Role | What they receive |
|---|---|---|
| Roxadustat | Active comparator | The group will receive Roxadustat (Evrenzo) three times weekly at an initial dose of 70mg (for body weight <100.0 kg) or 100 mg (for body weight weight ≥100.0 kg). The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl. Receives: Drug: Roxadustat |
| Darbepoietin alpha | Active comparator | The control group will receive darbepoietin alpha (Aranesp) s.c. 0.45mg/kg once a week. The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl. Receives: Drug: Darbepoietin Alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in kidney oxygenation levels
Kidney oxygenation will be evaluated using BOLD-MRI prior to start of therapy, and once again after 24 weeks of treatment with either RD or DA. Primary endpoint is the change in medullary and cortical R2* (inversely proportional to the tissue oxygenation content) after 24 weeks.
Measured: 24 Weeks
Secondary outcomes (2)
Change in albuminuria
Secondary endpoint will be albuminuria after 24 weeks of either treatment
Measured: 24 Weeks
Change in urinary reactive oxygen species (ROS)
Secondary endpoints will be urinary levels of ROS (evaluated by electron paramagnetic resonance (EPR) spectroscopy with CPH spin probes).
Measured: 24 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2023
- Study start1 Jun 2025 (estimated)
- Primary completion1 Jan 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Diabetes ComplicationsStudies of the same condition, open and under way.
- More trials run by Region StockholmThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The research design is a randomized prospective, open-label study with parallel groups of 15 patients/group with non-dialysis dependent DKD CKD stage 3-4 with Hb \<10g/dl.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Region Stockholm
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Sergiu Catrina, Ass. Proff., Principal investigator, Karolinska institute, Centre for diabetes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05810311
- Sponsor's protocol ID
- FOXTROT
- Acronym
- FOXTROT
- Status last verified
- Nov 2024
- First submitted
- 24 Mar 2023
- Last updated
- 19 Nov 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Catrina SB, Zheng X. Hypoxia and hypoxia-inducible factors in diabetes and its complications. Diabetologia. 2021 Apr;64(4):709-716. doi: 10.1007/s00125-021-05380-z. Epub 2021 Jan 26.
PubMed 33496820Sebastiani G, Grieco FA, Spagnuolo I, Galleri L, Cataldo D, Dotta F. Increased expression of microRNA miR-326 in type 1 diabetic patients with ongoing islet autoimmunity. Diabetes Metab Res Rev. 2011 Nov;27(8):862-6. doi: 10.1002/dmrr.1262.
PubMed 22069274Ruiter MS, van Golde JM, Schaper NC, Stehouwer CD, Huijberts MS. Diabetes impairs arteriogenesis in the peripheral circulation: review of molecular mechanisms. Clin Sci (Lond). 2010 Jun 8;119(6):225-38. doi: 10.1042/CS20100082.
PubMed 20545627Flyvbjerg A. Diabetic angiopathy, the complement system and the tumor necrosis factor superfamily. Nat Rev Endocrinol. 2010 Feb;6(2):94-101. doi: 10.1038/nrendo.2009.266.
PubMed 20098449Friederich M, Fasching A, Hansell P, Nordquist L, Palm F. Diabetes-induced up-regulation of uncoupling protein-2 results in increased mitochondrial uncoupling in kidney proximal tubular cells. Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):935-40. doi: 10.1016/j.bbabio.2008.03.030. Epub 2008 Apr 7.
PubMed 18439413Koyasu S, Kobayashi M, Goto Y, Hiraoka M, Harada H. Regulatory mechanisms of hypoxia-inducible factor 1 activity: Two decades of knowledge. Cancer Sci. 2018 Mar;109(3):560-571. doi: 10.1111/cas.13483. Epub 2018 Jan 27.
PubMed 29285833Xia X, Lemieux ME, Li W, Carroll JS, Brown M, Liu XS, Kung AL. Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4260-5. doi: 10.1073/pnas.0810067106. Epub 2009 Mar 2.
PubMed 19255431Elson DA, Ryan HE, Snow JW, Johnson R, Arbeit JM. Coordinate up-regulation of hypoxia inducible factor (HIF)-1alpha and HIF-1 target genes during multi-stage epidermal carcinogenesis and wound healing. Cancer Res. 2000 Nov 1;60(21):6189-95.
PubMed 11085544Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, Capla JM, Galiano RD, Levine JP, Gurtner GC. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004 Aug;10(8):858-64. doi: 10.1038/nm1075. Epub 2004 Jul 4.
PubMed 15235597Catrina SB. Impaired hypoxia-inducible factor (HIF) regulation by hyperglycemia. J Mol Med (Berl). 2014 Oct;92(10):1025-34. doi: 10.1007/s00109-014-1166-x. Epub 2014 Jun 12.
PubMed 25027070Palm F, Cederberg J, Hansell P, Liss P, Carlsson PO. Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension. Diabetologia. 2003 Aug;46(8):1153-60. doi: 10.1007/s00125-003-1155-z. Epub 2003 Jul 17.
PubMed 12879251Semenza GL. Pharmacologic Targeting of Hypoxia-Inducible Factors. Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:379-403. doi: 10.1146/annurev-pharmtox-010818-021637.
PubMed 30625281Pruijm M, Mendichovszky IA, Liss P, Van der Niepen P, Textor SC, Lerman LO, Krediet CTP, Caroli A, Burnier M, Prasad PV. Renal blood oxygenation level-dependent magnetic resonance imaging to measure renal tissue oxygenation: a statement paper and systematic review. Nephrol Dial Transplant. 2018 Sep 1;33(suppl_2):ii22-ii28. doi: 10.1093/ndt/gfy243.
PubMed 30137579
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Roxadustat on the Levels of Renal Oxygenation in Patients With Diabetes Nephropathy (FOXTROT)
- ClinicalTrials.gov ID
- NCT05810311
- Acronym / sponsor ID
- FOXTROT / FOXTROT
- Keywords
- HIF, Hypoxia, Diabetes mellitus, Nephropathy, BOLD-MRI, Kidney oxygenation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Region StockholmOther government
- Study start
- 1 Jun 2025 (estimated)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 12 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.
The study will investigate if treatment with Roxadustat improves kidney oxygenation in diabetic patients with nephropathy receiving treatment for renal anemia, compared to patients receiving treatment with darbepoetin alpha.
Participants will be randomized to either treatment, and receive equal care for renal anemia. Kidney oxygenation will be examined before treatment start and after 24 weeks using BOLD-MRI (blood oxygen level-defendant MRI), a non-invasive method available for measurement of tissue oxygenation levels that is comparable with direct invasive measurement of partial oxygen pressure. Blood and urin samples will be collected in connection to these visits. The primary endpoint is the change in medullary and cortical R2* (inversely proportional to the tissue oxygenation content) after 24 weeks. Secondary endpoints will be albuminuria and urinary levels of ROS (evaluated by electron paramagnetic resonance (EPR) spectroscopy with CPH spin probes).
Detailed description
Aims
The general aim of this study is to investigate the effects of systemic administration of Evrenzo (Roxadustat [RD]) or Aranesp (darbepoetin alpha [DA]) on the levels of renal oxygenation in patients with diabetic nephropathy and associated anemia.
The investigation will elucidate if RD, a prolyl-hydroxylase (PHD) inhibitor and subsequent Hypoxia-Inducible Factor 1 (HIF) activator, can reduce renal hypoxia, compared to DA, which lacks effects on HIF.
Background
Diabetes complications represent a huge health problem and concern for modern diabetes therapy, with dramatic consequences for the affected individuals and society.
Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and accounts for a high morbidity and mortality rate in patients with diabetes. Today, the treatment for DKD focuses on optimizing the patients' metabolic control, blood lipid levels and blood pressure, which unfortunately is optimally achieved in just a restricted portion of patients (1). Thus, there is a great need of identifying novel therapies that could improve or prevent progression DKD.
While hyperglycemia is the major factor contributing to the development of diabetes complications, the role of hypoxia has recently become increasingly evident as another central factor in all diabetes complications (2). Several effects may contribute to the development of hypoxia in diabetes, including deficient blood supply secondary to micro- and macro-vascular disease, poor local oxygen diffusion secondary to local oedema, or as a result of increased oxygen consumption (3, 4, 5, 6).
HIF-1, a heterodimeric transcription factor, is a central regulator of cellular adaptive response to hypoxia (7). HIF consists of two subunits (alpha and beta), both constitutively expressed in mammalian cells. In normoxia, HIF-1alpha is continuously degraded by the ubiquitin-proteasome system because of the oxygen-dependent hydroxylation of two key proline residues catalyzed by a group of enzymes known as prolyl-hydroxylases (PHDs) (7). Upon hypoxia, this degradation pathway is suppressed and HIF-1alpha is stabilized, translocates to the nucleus where it dimerizes with HIF-1beta and induces the expression of more than 800 genes involved in angiogenesis, glycolytic energy metabolism, proliferation and survival that enables the cells to adapt to reduced oxygen availability (8, 9). HIF-1 is central for expression of several angiogenic growth factors (e.g., VEGF, erythropoietin (EPO), stromal cell-derived factor-1alpha) (10).
Lately, accumulating evidence points to a defective cellular response to hypoxia in diabetes. This defective hypoxia response has been shown to be present in all tissues that develop complications in both animal models for diabetes and in patients with diabetes as a consequence of impaired HIF signaling, and there is a direct suppressive effect of hyperglycemia on HIF function (11). Studies in animal models of diabetes have demonstrated that restoring HIF function in hyperglycemia can prevent the development of multiple diabetes complications, including DKD (7).
RD is a PHD inhibitor that stabilizes HIF-1 by preventing PHD dependent degradation of HIF-1alpha, and has recently been approved for treatment of renal anemia. As hypoxia plays a central pathogenic role even in the early stages of DKD (12), and activation of HIF signaling has recently been demonstrated to have protective effects in animal models of DKD (13), it is of great interest to also investigate the potential role of RD as a targeted therapy for DKD in humans.
The presently proposed project aims to investigate the potential of RD to improve renal oxygenation in patients with DKD and anemia, compared to DA which lacks the above-mentioned effects on HIF and is an alternative treatment for the same condition. To examine this the investigators plan to use BOLD-MRI (blood oxygen level-defendant MRI), a non-invasive method available for measurement of tissue oxygenation levels that is comparable with direct invasive measurement of partial oxygen pressure (14).
Research design
The research design is a randomized prospective, open-label study with parallel groups of 15 participants/group with non-dialysis dependent DKD CKD stage 3-4 with Hb <10g/dl (the level of Hb recommended for RD/DA treatment). One group will receive Roxadustat (Evrenzo) three times weekly at an initial dose of 70mg (for body weight <100.0 kg) or 100 mg (for body weight weight ≥100.0 kg). The control group will receive darbepoietin alpha (Aranesp) s.c. 0.45mg/kg once a week. The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl.
Kidney oxygenation will be evaluated using BOLD-MRI prior to start of therapy, and once again after 24 weeks of treatment with either RD or DA. Primary endpoint is the change in medullary and cortical R2* (inversely proportional to the tissue oxygenation content) after 24 weeks. Secondary endpoints will be albuminuria and urinary levels of ROS (evaluated by electron paramagnetic resonance (EPR) spectroscopy with CPH spin probes).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The research design is a randomized prospective, open-label study with parallel groups of 15 patients/group with non-dialysis dependent DKD CKD stage 3-4 with Hb <10g/dl.
| Arm | Type | Receives |
|---|---|---|
| Roxadustat | Active comparator | Drug: RoxadustatThe group will receive Roxadustat (Evrenzo) three times weekly at an initial dose of 70mg (for body weight <100.0 kg) or 100 mg (for body weight weight ≥100.0 kg). The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl. |
| Darbepoietin alpha | Active comparator | Drug: Darbepoietin AlfaThe control group will receive darbepoietin alpha (Aranesp) s.c. 0.45mg/kg once a week. The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Diabetes mellitus with anemia caused by DKD, and indication for treatment with erythropoetin/erythropoietin-stimulating drugs.
- Age 18-75
- HbA1c >55
- Diabetes duration 10+ years.
- Chronic kidney disease (CKD) stage 3-4
Key exclusion criteria (17 listed)
- Anemia not related to CKD.
- Dialysis dependent CKD
- Currently treated for renal anemia using erythropoietin-stimulating drugs
- Infections during the last 30 days.
- Severe hypertension (≥180mmHg systolic or >110mmHg diastolic blood pressure)
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 |
|---|---|---|
| RoxadustatAlso: EvrenzoThe group will receive Roxadustat (Evrenzo) three times weekly at an initial dose of 70mg (for body weight <100.0 kg) or 100 mg (for body weight weight ≥100.0 kg). The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl. The aim is to investigate the effects of systemic administration of Evrenzo (Roxadustat [RD]) or Aranesp (darbepoetin alpha [DA]) on the levels of renal oxygenation in patients with diabetic nephropathy and associated anemia. | Drug | Roxadustat |
| Darbepoietin AlfaAlso: AranespThe control group will receive darbepoietin alpha (Aranesp) s.c. 0.45mg/kg once a week. The dosage for both arms will be adjusted to keep Hb at the recommended levels between 11-12g/dl. The aim is to investigate the effects of systemic administration of Evrenzo (Roxadustat [RD]) or Aranesp (darbepoetin alpha [DA]) on the levels of renal oxygenation in patients with diabetic nephropathy and associated anemia. | Drug | Darbepoietin alpha |
Primary outcome
Change in kidney oxygenation levels
Time frame: 24 Weeks
Kidney oxygenation will be evaluated using BOLD-MRI prior to start of therapy, and once again after 24 weeks of treatment with either RD or DA. Primary endpoint is the change in medullary and cortical R2* (inversely proportional to the tissue oxygenation content) after 24 weeks.
2 secondary outcomes
Change in albuminuria
Time frame: 24 Weeks
Change in urinary reactive oxygen species (ROS)
Time frame: 24 Weeks
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 19 Nov 2024.
- Background: PubMed 33496820Catrina SB, Zheng X. Hypoxia and hypoxia-inducible factors in diabetes and its complications. Diabetologia. 2021 Apr;64(4):709-716. doi: 10.1007/s00125-021-05380-z. Epub 2021 Jan 26.
- Background: PubMed 22069274Sebastiani G, Grieco FA, Spagnuolo I, Galleri L, Cataldo D, Dotta F. Increased expression of microRNA miR-326 in type 1 diabetic patients with ongoing islet autoimmunity. Diabetes Metab Res Rev. 2011 Nov;27(8):862-6. doi: 10.1002/dmrr.1262.
- Background: PubMed 20545627Ruiter MS, van Golde JM, Schaper NC, Stehouwer CD, Huijberts MS. Diabetes impairs arteriogenesis in the peripheral circulation: review of molecular mechanisms. Clin Sci (Lond). 2010 Jun 8;119(6):225-38. doi: 10.1042/CS20100082.
- Background: PubMed 20098449Flyvbjerg A. Diabetic angiopathy, the complement system and the tumor necrosis factor superfamily. Nat Rev Endocrinol. 2010 Feb;6(2):94-101. doi: 10.1038/nrendo.2009.266.
- Background: PubMed 18439413Friederich M, Fasching A, Hansell P, Nordquist L, Palm F. Diabetes-induced up-regulation of uncoupling protein-2 results in increased mitochondrial uncoupling in kidney proximal tubular cells. Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):935-40. doi: 10.1016/j.bbabio.2008.03.030. Epub 2008 Apr 7.
- Background: PubMed 29285833Koyasu S, Kobayashi M, Goto Y, Hiraoka M, Harada H. Regulatory mechanisms of hypoxia-inducible factor 1 activity: Two decades of knowledge. Cancer Sci. 2018 Mar;109(3):560-571. doi: 10.1111/cas.13483. Epub 2018 Jan 27.
- Background: PubMed 19255431Xia X, Lemieux ME, Li W, Carroll JS, Brown M, Liu XS, Kung AL. Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4260-5. doi: 10.1073/pnas.0810067106. Epub 2009 Mar 2.
- Background: PubMed 11085544Elson DA, Ryan HE, Snow JW, Johnson R, Arbeit JM. Coordinate up-regulation of hypoxia inducible factor (HIF)-1alpha and HIF-1 target genes during multi-stage epidermal carcinogenesis and wound healing. Cancer Res. 2000 Nov 1;60(21):6189-95.
- Background: PubMed 15235597Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, Capla JM, Galiano RD, Levine JP, Gurtner GC. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004 Aug;10(8):858-64. doi: 10.1038/nm1075. Epub 2004 Jul 4.
- Background: PubMed 25027070Catrina SB. Impaired hypoxia-inducible factor (HIF) regulation by hyperglycemia. J Mol Med (Berl). 2014 Oct;92(10):1025-34. doi: 10.1007/s00109-014-1166-x. Epub 2014 Jun 12.
- Background: PubMed 12879251Palm F, Cederberg J, Hansell P, Liss P, Carlsson PO. Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension. Diabetologia. 2003 Aug;46(8):1153-60. doi: 10.1007/s00125-003-1155-z. Epub 2003 Jul 17.
- Background: PubMed 30625281Semenza GL. Pharmacologic Targeting of Hypoxia-Inducible Factors. Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:379-403. doi: 10.1146/annurev-pharmtox-010818-021637.
- Nationella Diabetesregistret 2023Link provided by the sponsor.
- 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.
Andris Elksnis, PhD contact
Sergiu Catrina, Ass. Proff. principal investigator
Karolinska institute, Centre for diabetes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Roxadustat and Darbepoietin Alfa in people with Diabetes Complications and Diabetes; Nephropathy (Manifestation), run by Region Stockholm at 1 site in Sweden.
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 13 inclusion and 17 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: opening soon, as of the sponsor's last update on 19 Nov 2024. 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 Sweden. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Sergiu Catrina, Ass. prof. (+46-8-51775449, sergiu.catrina@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in kidney oxygenation levels (time frame: 24 Weeks). 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 NCT05810311, which also lists 13 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 19 Nov 2024.