Anemia of Chronic Kidney DiseaseNCT03193073
Anemia Correction and Fibroblast Growth Factor 23 Levels in Chronic Kidney Disease , and Renal Transplant Patient
A study testing detailed echocardiography, serum fibroblast growth factor-23 and flow mediated dilatation of forearm in people with Anemia of Chronic Kidney Disease and Endothelial Dysfunction, run by Omnia Mohammed Hashem at 1 site in Egypt.
Trial summary
The fibroblast growth factor-23-bone-kidney axis is part of newly discovered biological systems linking bone to other organ functions through a complex endocrine network that is integrated with the parathormone/vitamin D axis and which plays an equally important role in health and disease . Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Anemia of Chronic Kidney Disease, Endothelial Dysfunction, Left Ventricular Hypertrophy
- What is being tested?
- detailed echocardiography, serum fibroblast growth factor-23 and flow mediated dilatation of forearm
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Sep 2018to 1 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- All patients:
- Above 18 years old
- Diagnosed as CKD, and renal transplanted patients at Assiut University Hospital in the period 2017-2020 .
Who cannot join
- Severely hypocalcaemic patients < 7mg/dl.
- Severely hyperphosphatemic patients >7 mg/dl .
- Uncontrolled hypertensive patients ( more than 3 antihypertensive drugs).
- Uncontrolled diabetic patients HBA1C >8 .
- Blood transfusion dependent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Anemia Correction and Fibroblast Growth Factor 23 Levels in Left Ventricular Hypertrophy, and Early Endothelial Dysfunction in Chronic Kidney Disease, and Renal Transplant Patient
The fibroblast growth factor-23-bone-kidney axis is part of newly discovered biological systems linking bone to other organ functions through a complex endocrine network that is integrated with the parathormone/vitamin D axis and which plays an equally important role in health and disease . Most of the known physiological function of fibroblast growth factor 23 to regulate mineral metabolism can be accounted for by actions of this hormone on the kidney.In a recent experimental study, fibroblast growth factor-23 was shown to cause pathological hypertrophy in rat cardiomyocytes by "calcineurin-nuclear factor of activated T cells" and treatment with fibroblast growth factor -blockers reduced left ventricular hypertrophy in experimental models of chronic renal failure.The current hypothesis is that, in healthy individuals, iron deficiency stimulates increased production of fibroblast growth factor23. At the same time, iron is thought to be the cofactor of enzymes taking part in the degradation of intact fibroblast growth factor-23 and thought to have a role in the excretion of degraded FGF-23 parts .Studies speculated that Angiotensin Converting Enzyme inhibitors may exert their anti-proteinuria effects at least in part by reducing serum fibroblast growth factor-23 levels although it is difficult from the results of this study to understand which comes first and brings about the other; decrease in proteinuria or fibroblast growth factor-23. Available evidence points to the deleterious effects of increased fibroblast growth factor-23 level in proteinuria, but the precise molecular mechanism still remains to be explored. An intricate and close association exists among parathormone, phosphorus, active vitamin D with FGF23, but the independent role of the latter on proteinuria is the least explored. Elaborately conducted studies that control effects of confounding factors adequately are needed to demonstrate the independent pathogenic role of FGF23.
Read the detailed description
- To study the effect of anemia correction and left ventricular hypertrophy in Chronic Kidney Disease patients and renal transplant patients .
- To study the relation of fibroblast growth factor and Left ventricular hypertrophy in Chronic kidney disease and renal transplant patients.
- To study the relation between fibroblast growth factor 23 and early endothelial dysfunction in both Chronic kidney disease and renal transplant patients.
- Conditions
- Anemia of Chronic Kidney Disease, Endothelial Dysfunction, Left Ventricular Hypertrophy, Fibroblast Growth Factor 23
- Being tested
- detailed echocardiography, serum fibroblast growth factor-23, flow mediated dilatation of forearm
- Medical subject headings
- Hypertrophy, Left Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
detailed echocardiographyDiagnostic test
Detailed Echocardiography including ejection fraction, interventricular septum thickness, posterior wall thickness, left ventricular end -diastolic and end- systolic diameter and left ventricular mass index will be correlated with body surface area for both groups serum FGF-23
serum fibroblast growth factor-23Diagnostic test
serum levels of FGF-23
flow mediated dilatation of forearmDiagnostic test
superficial sonar assess the diameter of brachial vessel on exposure to stress
| Study group | Role | What they receive |
|---|---|---|
| CKD patients with different stages | Active comparator | 1. Full clinical history and through clinical examination.
2. Full blood count at time of diagnosis and 3 months after initiation of treatment with iron and erythropoietin Stimulating agents.
3. Iron study at time of diagnosis and 3 months after treatment .
4. Serum calcium , phosphorus, intact Parathrmone hormone. 5-24- urinary proteins or Albumin Creatinine ratio every month (for 3 months )then every 3 months (1 st year), then annually.
6- Lipid profile . 7-Estimated glomerular filtration rate by MDRD equation . Receives: Diagnostic Test: detailed echocardiography; Diagnostic Test: serum fibroblast growth factor-23; Diagnostic Test: flow mediated dilatation of forearm |
| Newly renal transplanted patients . | Active comparator | 1. Full clinical history and through clinical examination.
2. Pre transplant Serum calcium , phosphorus , I Parathrmone hormone , serial measures every / 3 months for 2 years.
3. Pre-transplant full blood count serial measures every / 3 months for 2 years.
4. Pre transplant serum Iron study and annually for 2 years.
5. 24- urinary proteins or albumin-creatinine ratio every month (for 3 months )then every 3 months (1 st year), then annually.
6. Post-transplant serum FGF-23 (as independent risk factor) at 6months.
7. Different immunosuppressive protocols.
8. Pre-transplant panel reactive antibody,donor-specific antibody Receives: Diagnostic Test: detailed echocardiography; Diagnostic Test: serum fibroblast growth factor-23; Diagnostic Test: flow mediated dilatation of forearm |
What is being measured
The primary outcome is the main question the study is designed to answer.
if change of in Hemoglobin level and correction of anemia associated with change in the left ventricular outcomes
measure the left ventricular mass index (gm/m2)
Measured: measures at time of diagnosis then after 3 months
the relationship between the FGF-23 and degree of left ventricular dysfunction
measure FGF-23 level in (pg/ml)
Measured: measure at time of diagnosis
the relationship between FGF-23 level and early endothelial dysfunction
change in arterial diameter in mm
Measured: at time of diagnosis in chronic kidney disease / after 6 months in renal transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study start1 Sep 2018 (estimated)
- Primary completion1 Sep 2020 (estimated)
- Study completion1 Dec 2020 (estimated)
Why it stopped: problem in funding which will be solved by the end of August
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Anemia of Chronic Kidney 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- two groups of patients (group A: CKD and group B newly transplanted patients) are assigned for detailed echocardiography , serum FGF-23, flow mediated dilatation of the forearm before anaemia correction in group A and renal transplant in group B . Also assesment of FGF-23 in different stages of group A, assessment of FGF-23 before and after renal transplant
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Omnia Mohammed Hashem
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Omnia Mohammed Hashem, Assiut University
- Investigators
- Mohammed Ali Tohamy, professor, Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03193073
- Sponsor's protocol ID
- 17200031
- Status last verified
- Jun 2018
- First submitted
- 26 May 2017
- Last updated
- 27 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Grabner A, Amaral AP, Schramm K, Singh S, Sloan A, Yanucil C, Li J, Shehadeh LA, Hare JM, David V, Martin A, Fornoni A, Di Marco GS, Kentrup D, Reuter S, Mayer AB, Pavenstadt H, Stypmann J, Kuhn C, Hille S, Frey N, Leifheit-Nestler M, Richter B, Haffner D, Abraham R, Bange J, Sperl B, Ullrich A, Brand M, Wolf M, Faul C. Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy. Cell Metab. 2015 Dec 1;22(6):1020-32. doi: 10.1016/j.cmet.2015.09.002. Epub 2015 Oct 1.
PubMed 26437603Torun D, Yildiz I, Micozkadioglu H, Nursal GN, Yigit F, Ozelsancak R. The effects of cinacalcet treatment on bone mineral metabolism, anemia parameters, left ventricular mass index and parathyroid gland volume in hemodialysis patients with severe secondary hyperparathyroidism. Saudi J Kidney Dis Transpl. 2016 Jan;27(1):15-22. doi: 10.4103/1319-2442.174053.
PubMed 26787561Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res. 2013 Aug;28(8):1793-803. doi: 10.1002/jbmr.1923.
PubMed 23505057Eser B, Yayar O, Buyukbakkal M, Erdogan B, Ercan Z, Merhametsiz O, Haspulat A, Oguz EG, Dogan I, Canbakan B, Ayli MD. Fibroblast growth factor is associated to left ventricular mass index, anemia and low values of transferrin saturation. Nefrologia. 2015;35(5):465-72. doi: 10.1016/j.nefro.2015.06.025. Epub 2015 Sep 26. English, Spanish.
PubMed 26394828Io H, Aizawa M, Funabiki K, Horikoshi S, Tomino Y. Impact of anaemia treatment for left ventricular remodelling prior to initiation of dialysis in chronic kidney disease patients: Efficacy and stability of long acting erythropoietin stimulating agents. Nephrology (Carlton). 2015 Dec;20 Suppl 4:7-13. doi: 10.1111/nep.12640.
PubMed 26439537
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Anemia Correction and Fibroblast Growth Factor 23 Levels in Left Ventricular Hypertrophy, and Early Endothelial Dysfunction in Chronic Kidney Disease, and Renal Transplant Patient
- ClinicalTrials.gov ID
- NCT03193073
- Acronym / sponsor ID
- 17200031
- Conditions
- Anemia of Chronic Kidney Disease, Endothelial Dysfunction, Left Ventricular Hypertrophy, Fibroblast Growth Factor 23
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: problem in funding which will be solved by the end of August
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Omnia Mohammed HashemUniversity, hospital or other
- Study start
- 1 Sep 2018 (estimated)
- Primary completion
- 1 Sep 2020 (estimated)
- Study completion
- 1 Dec 2020 (estimated)
- First posted
- 20 Jun 2017 (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 fibroblast growth factor-23-bone-kidney axis is part of newly discovered biological systems linking bone to other organ functions through a complex endocrine network that is integrated with the parathormone/vitamin D axis and which plays an equally important role in health and disease . Most of the known physiological function of fibroblast growth factor 23 to regulate mineral metabolism can be accounted for by actions of this hormone on the kidney.In a recent experimental study, fibroblast growth factor-23 was shown to cause pathological hypertrophy in rat cardiomyocytes by "calcineurin-nuclear factor of activated T cells" and treatment with fibroblast growth factor -blockers reduced left ventricular hypertrophy in experimental models of chronic renal failure.The current hypothesis is that, in healthy individuals, iron deficiency stimulates increased production of fibroblast growth factor23. At the same time, iron is thought to be the cofactor of enzymes taking part in the degradation of intact fibroblast growth factor-23 and thought to have a role in the excretion of degraded FGF-23 parts .Studies speculated that Angiotensin Converting Enzyme inhibitors may exert their anti-proteinuria effects at least in part by reducing serum fibroblast growth factor-23 levels although it is difficult from the results of this study to understand which comes first and brings about the other; decrease in proteinuria or fibroblast growth factor-23. Available evidence points to the deleterious effects of increased fibroblast growth factor-23 level in proteinuria, but the precise molecular mechanism still remains to be explored. An intricate and close association exists among parathormone, phosphorus, active vitamin D with FGF23, but the independent role of the latter on proteinuria is the least explored. Elaborately conducted studies that control effects of confounding factors adequately are needed to demonstrate the independent pathogenic role of FGF23.
Detailed description
- To study the effect of anemia correction and left ventricular hypertrophy in Chronic Kidney Disease patients and renal transplant patients .
- To study the relation of fibroblast growth factor and Left ventricular hypertrophy in Chronic kidney disease and renal transplant patients.
- To study the relation between fibroblast growth factor 23 and early endothelial dysfunction in both Chronic kidney disease and renal transplant patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- two groups of patients (group A: CKD and group B newly transplanted patients) are assigned for detailed echocardiography , serum FGF-23, flow mediated dilatation of the forearm before anaemia correction in group A and renal transplant in group B . Also assesment of FGF-23 in different stages of group A, assessment of FGF-23 before and after renal transplant
| Arm | Type | Receives |
|---|---|---|
| CKD patients with different stages | Active comparator | Diagnostic Test: detailed echocardiography, Diagnostic Test: serum fibroblast growth factor-23, Diagnostic Test: flow mediated dilatation of forearm1. Full clinical history and through clinical examination. 2. Full blood count at time of diagnosis and 3 months after initiation of treatment with iron and erythropoietin Stimulating agents. 3. Iron study at time of diagnosis and 3 months after treatment . 4. Serum calcium , phosphorus, intact Parathrmone hormone. 5-24- urinary proteins or Albumin Creatinine ratio every month (for 3 months )then every 3 months (1 st year), then annually. 6- Lipid profile . 7-Estimated glomerular filtration rate by MDRD equation . |
| Newly renal transplanted patients . | Active comparator | Diagnostic Test: detailed echocardiography, Diagnostic Test: serum fibroblast growth factor-23, Diagnostic Test: flow mediated dilatation of forearm1. Full clinical history and through clinical examination. 2. Pre transplant Serum calcium , phosphorus , I Parathrmone hormone , serial measures every / 3 months for 2 years. 3. Pre-transplant full blood count serial measures every / 3 months for 2 years. 4. Pre transplant serum Iron study and annually for 2 years. 5. 24- urinary proteins or albumin-creatinine ratio every month (for 3 months )then every 3 months (1 st year), then annually. 6. Post-transplant serum FGF-23 (as independent risk factor) at 6months. 7. Different immunosuppressive protocols. 8. Pre-transplant panel reactive antibody,donor-specific antibody |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Above 18 years old
- Diagnosed as CKD, and renal transplanted patients at Assiut University Hospital in the period 2017-2020 .
Key exclusion criteria (5 listed)
- Severely hypocalcaemic patients < 7mg/dl.
- Severely hyperphosphatemic patients >7 mg/dl .
- Uncontrolled hypertensive patients ( more than 3 antihypertensive drugs).
- Uncontrolled diabetic patients HBA1C >8 .
- Blood transfusion dependent
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 |
|---|---|---|
| detailed echocardiographyDetailed Echocardiography including ejection fraction, interventricular septum thickness, posterior wall thickness, left ventricular end -diastolic and end- systolic diameter and left ventricular mass index will be correlated with body surface area for both groups serum FGF-23 | Diagnostic test | CKD patients with different stages, Newly renal transplanted patients . |
| serum fibroblast growth factor-23serum levels of FGF-23 | Diagnostic test | CKD patients with different stages, Newly renal transplanted patients . |
| flow mediated dilatation of forearmsuperficial sonar assess the diameter of brachial vessel on exposure to stress | Diagnostic test | CKD patients with different stages, Newly renal transplanted patients . |
Primary outcome
if change of in Hemoglobin level and correction of anemia associated with change in the left ventricular outcomes
Time frame: measures at time of diagnosis then after 3 months
measure the left ventricular mass index (gm/m2)
the relationship between the FGF-23 and degree of left ventricular dysfunction
Time frame: measure at time of diagnosis
measure FGF-23 level in (pg/ml)
the relationship between FGF-23 level and early endothelial dysfunction
Time frame: at time of diagnosis in chronic kidney disease / after 6 months in renal transplant
change in arterial diameter in mm
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2018.
- Results publication: PubMed 26437603Grabner A, Amaral AP, Schramm K, Singh S, Sloan A, Yanucil C, Li J, Shehadeh LA, Hare JM, David V, Martin A, Fornoni A, Di Marco GS, Kentrup D, Reuter S, Mayer AB, Pavenstadt H, Stypmann J, Kuhn C, Hille S, Frey N, Leifheit-Nestler M, Richter B, Haffner D, Abraham R, Bange J, Sperl B, Ullrich A, Brand M, Wolf M, Faul C. Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy. Cell Metab. 2015 Dec 1;22(6):1020-32. doi: 10.1016/j.cmet.2015.09.002. Epub 2015 Oct 1.
- Results publication: PubMed 26787561Torun D, Yildiz I, Micozkadioglu H, Nursal GN, Yigit F, Ozelsancak R. The effects of cinacalcet treatment on bone mineral metabolism, anemia parameters, left ventricular mass index and parathyroid gland volume in hemodialysis patients with severe secondary hyperparathyroidism. Saudi J Kidney Dis Transpl. 2016 Jan;27(1):15-22. doi: 10.4103/1319-2442.174053.
- Results publication: PubMed 23505057Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res. 2013 Aug;28(8):1793-803. doi: 10.1002/jbmr.1923.
- Results publication: PubMed 26394828Eser B, Yayar O, Buyukbakkal M, Erdogan B, Ercan Z, Merhametsiz O, Haspulat A, Oguz EG, Dogan I, Canbakan B, Ayli MD. Fibroblast growth factor is associated to left ventricular mass index, anemia and low values of transferrin saturation. Nefrologia. 2015;35(5):465-72. doi: 10.1016/j.nefro.2015.06.025. Epub 2015 Sep 26. English, Spanish.
- Results publication: PubMed 26439537Io H, Aizawa M, Funabiki K, Horikoshi S, Tomino Y. Impact of anaemia treatment for left ventricular remodelling prior to initiation of dialysis in chronic kidney disease patients: Efficacy and stability of long acting erythropoietin stimulating agents. Nephrology (Carlton). 2015 Dec;20 Suppl 4:7-13. doi: 10.1111/nep.12640.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Mohammed Ali Tohamy, professor study director
Assiut University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing detailed echocardiography, serum fibroblast growth factor-23 and flow mediated dilatation of forearm in people with Anemia of Chronic Kidney Disease and Endothelial Dysfunction, run by Omnia Mohammed Hashem at 1 site in Egypt.
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 3 inclusion and 5 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: paused, as of the sponsor's last update on 27 Jun 2018. 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 Egypt. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
if change of in Hemoglobin level and correction of anemia associated with change in the left ventricular outcomes (time frame: measures at time of diagnosis then after 3 months). The study lists 3 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 NCT03193073, which also lists 5 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 27 Jun 2018.