Chronic Kidney Disease stage3NCT04961931
Effect of Empagliflozin on Urinary Excretion of Adenosine and Osteocyte Function in Patients With Chronic Kidney Disease
A study testing Empagliflozin 10 MG in people with Chronic Kidney Disease stage3, run by Medical University of Lodz at 1 site in Poland.
Trial summary
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of orally drugs for the treatment of type 2 diabetes. These drugs decrease plasma glucose levels by inhibiting its reabsorption in the proximal tubules of the kidney. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Disease stage3
- What is being tested?
- Empagliflozin 10 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 sitePoland
- Study dates
- 1 Jan 2019to 31 Aug 2021
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- type 2 diabetes complicated by diabetic nephropathy (first group), non-diabetic nephropathy (second group) or healthy subjects
- Angiotensin-converting enzyme inhibitor or antagonists of angiotensin receptor blockers in the stable dose for the 4 months
- age 18 - 70 years
- stable clinical condition for the last 3 months
- GFR 25-60 ml / min / 1.73 m2
- proteinuria 0.5-3 g / day
Who cannot join
- diabetes mellitus other than t.2
- have taken SGLT2 inhibitors in the last 4 weeks or have ever had an intolerance to SGLT2 inhibitors in the past
- acute kidney damage
- systolic blood pressure <90 mmHg
- Cancer
- acute inflammation
Show all 10Show fewer
- liver failure
- heart failure> 2. NYHA grade
- pregnancy
- patients with impaired consciousness and testers with insufficient management in the past.
Trial locations and contacts
1 site in 1 country.
Poland1 site, 1 recruiting
- Recruiting
Department of Nephrology, Hypertension and Kidney Transplantation
Lodz, 90-153
MD, 00482014400, nefro@wp.pl
Anna Masajtis-Zagajewska, MD, +48608558005, anna.masajtis-zagajewska@umed.lodz.pl
About this study
Official title: Effect of Empagliflozin on Urinary Excretion of Adenosine and on Markers of Osteocyte Function and Glomerular Damage in Diabetic and Non-diabetic Patients With Chronic Kidney Disease
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of orally drugs for the treatment of type 2 diabetes. These drugs decrease plasma glucose levels by inhibiting its reabsorption in the proximal tubules of the kidney. They have an attractive clinical efficacy profile, including glycemic control, weight loss, and lowering blood pressure. SGLT2 inhibitors have also been reported to reduce the risk of severe adverse cardiovascular events and progression of diabetic kidney disease. SGLT2 is expressed in the kidney, while its expression in other tissues is most likely negligible or absent.
SGLT2 dilates the supply vessels to the glomerulus thereby promoting hyperfiltration. In animal models SGLT2 has been shown to reduce the excretion of macular dense adenosine, which may contribute to the excessive glomerular filtration rate as a result of vasodilation of the afferent vessels. Adenosine, unlike other vascular regions, increases the tension in the walls of the vessels supplying blood to the glomerulus. The role of adenosine in humans in this regard is poorly defined, although treatment with empagliflozin has recently been shown to increase the urinary excretion of adenosine in type 1 diabetic patients with controlled hyperglycemia. Our working hypothesis is that the SGLT2 inhibitor empagliflozin may reduce the hyperfiltration of residual nephrons by increasing adenosine production, which affects the contraction of the afferent arterioles, and this effect occurs in various types of nephropathy.
In addition, it has been described that SGLT2 inhibitors may affect individual parameters of calcium-phosphate metabolism, leading to changes in bone mineral density and an increase in bone resorption marker SGLT2 inhibitors also stimulate renal, proximal phosphate reabsorption. Increased phosphate reabsorption triggers the secretion of fibroblast growth factor 23 (FGF23). FGF23 inhibits the production of 1,25-dihydroxyvitamin D (the biologically active form of vitamin D), which reduces the absorption of calcium from the gastrointestinal tract, thereby stimulating the secretion of parathyroid hormone (PTH). In the conducted studies, it was found that SGLT2 inhibitors increase the concentration of serum phosphorus, FGF23 in the plasma and PTH in the plasma, while lowering the level of 1,25-dihydroxyvitamin D.
Read the detailed description
The study will be prospective, interventional and will be conducted in two parallel groups selected on the basis of clinical diagnosis. It is planned to enroll 60 patients aged 18-70 years under outpatient nephrological care, with impaired excretory function of the kidneys (eGFR 20-60 ml / min / 1.73 m3), with proteinuria above 0.5-3 g / l in the morning urine sample , including 30 nondiabetic and 30 diabetic patients t.2 and 20 healthy control subjects (no microalbuminuria and no impaired renal function with eGFR> 90 ml / min / 1.73m3). After the patients are familiarized with the objectives of the study and the informed consent signed, the following procedures will be performed.
After signing the consent, basic biochemical tests will be performed in both groups to assess the concentration of protein, albumin, calcium, phosphate, adenosine and creatinine in the morning urine sample, creatinine, calcium, phosphate, PTH, bacterial alkaline phosphatase (BAP), 1.25 vitamin D, sclerostins, FGF23, serum Klotho proteins, eGFR, plasma glucose. The tests will be repeated after 7 days of taking empagliflozin in a dose of 10 mg a day. On days 1 and 7, patients will be given an intravenous glucose 5% solution at a dose of 240 mg glucose / kg body weight in the first 15 minutes to induce a controlled hyperglycaemia state in the first 15 minutes, this will increase their blood glucose by 125 mg / dL in 15 minutes followed by 10-12 mg glucose / kg body weight, under glycemic control to maintain a concentration of 200 mg / dL ± 5% for 120 minutes. Stability of serum glucose levels during this period will be maintained by adjusting the rate of intravenous glucose infusion based on blood glucose measurements, every 15 minutes. After 2 hours of infusion, additional blood will be drawn for the determination of glucose and renal parameters and after 100 ml of urine for determination. adenosine, albumin and creatinine concentrations. In healthy subjects from the control group, the above basic blood and urine biochemical tests will be performed once.
- Conditions
- Chronic Kidney Disease stage3
- Being tested
- Empagliflozin 10 MG
- Keywords
- SGLT2 inhibitors, adenosine, calcium-phosphate metabolism, chronic kidney disease, diabetes, non-diabetes, albuminuria
- Medical subject headings
- Renal Insufficiency, Chronic, Diabetes Mellitus, Albuminuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MGDrug
Also called Jardiance
After qualifying for the study all subjects received oral empagliflozin 10 mg once daily for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| diabetes group | Other | After qualifying for the study subjects with diabetes and chornic kidney disease received oral empagliflozin 10 mg once daily for 7 days. Receives: Drug: Empagliflozin 10 MG |
| non-diabetes group | Other | After qualifying for the study subjects with chronic kidney disease without diabetes received oral empagliflozin 10 mg once daily for 7 days. Receives: Drug: Empagliflozin 10 MG |
| control | Other | After qualifying for the study healthy subjects received oral empagliflozin 10 mg once daily for 7 days. Receives: Drug: Empagliflozin 10 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
albuminuria
ratio of albumin to creatinine in urine in mg/g
Measured: 7 days
serum calcium concentration
serum calcium level in mmol/l
Measured: 7 days
urine calcium concentration
level of calcium in urine in mmol/l
Measured: 7 days
urine adenosine
adenosine in urine in µmol/mmol creatinine
Measured: 7 days
urine phosphorus concetration
serum phosphorus level in mmol/l
Measured: 7 days
serum Fibroblast growth factor 23 concentration
serum Fibroblast growth factor 23 level in pg/ml
Measured: 7 days
serum parathormone concentration
serum parathormone level in pg/ml
Measured: 7 days
serum Klotho concentration
serum Klotho level in ng/ml
Measured: 7 days
serum Bone alkaline phosphatase concentration
serum Bone alkaline phosphatase level in µg/l
Measured: 7 days
serum 1,25(OH)2D concentration
serum 1,25(OH)2D level in pg/ml
Measured: 7 days
serum sclerostin concentration
serum sclerostin level in pmol/l
Measured: 7 days
urine phosphorus concetration
phosphorus in urine in mmol/l
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2021
- Study start1 Jan 2019
- Primary completion31 Aug 2021 (estimated)
- Study completion31 Aug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney Disease stage3Studies 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
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study will be prospective, interventional and will be conducted in two parallel groups selected on the basis of clinical diagnosis (diabetic nephropathy or other chronic nephropathies).
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Lodz
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michal Nowicki, Medical University of Lodz
- Investigators
- Ireneusz Staroń, Study chair, Medical University of Lodz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04961931
- Sponsor's protocol ID
- EMPA - 1 - AMZ
- Status last verified
- Jul 2021
- First submitted
- 30 Jun 2021
- Last updated
- 14 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Empagliflozin on Urinary Excretion of Adenosine and on Markers of Osteocyte Function and Glomerular Damage in Diabetic and Non-diabetic Patients With Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT04961931
- Acronym / sponsor ID
- EMPA - 1 - AMZ
- Conditions
- Chronic Kidney Disease stage3
- Keywords
- SGLT2 inhibitors, adenosine, calcium-phosphate metabolism, chronic kidney disease, diabetes, non-diabetes, albuminuria
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Medical University of LodzUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 31 Aug 2021 (estimated)
- Study completion
- 31 Aug 2021 (estimated)
- First posted
- 14 Jul 2021 (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.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of orally drugs for the treatment of type 2 diabetes. These drugs decrease plasma glucose levels by inhibiting its reabsorption in the proximal tubules of the kidney. They have an attractive clinical efficacy profile, including glycemic control, weight loss, and lowering blood pressure. SGLT2 inhibitors have also been reported to reduce the risk of severe adverse cardiovascular events and progression of diabetic kidney disease. SGLT2 is expressed in the kidney, while its expression in other tissues is most likely negligible or absent.
SGLT2 dilates the supply vessels to the glomerulus thereby promoting hyperfiltration. In animal models SGLT2 has been shown to reduce the excretion of macular dense adenosine, which may contribute to the excessive glomerular filtration rate as a result of vasodilation of the afferent vessels. Adenosine, unlike other vascular regions, increases the tension in the walls of the vessels supplying blood to the glomerulus. The role of adenosine in humans in this regard is poorly defined, although treatment with empagliflozin has recently been shown to increase the urinary excretion of adenosine in type 1 diabetic patients with controlled hyperglycemia. Our working hypothesis is that the SGLT2 inhibitor empagliflozin may reduce the hyperfiltration of residual nephrons by increasing adenosine production, which affects the contraction of the afferent arterioles, and this effect occurs in various types of nephropathy.
In addition, it has been described that SGLT2 inhibitors may affect individual parameters of calcium-phosphate metabolism, leading to changes in bone mineral density and an increase in bone resorption marker SGLT2 inhibitors also stimulate renal, proximal phosphate reabsorption. Increased phosphate reabsorption triggers the secretion of fibroblast growth factor 23 (FGF23). FGF23 inhibits the production of 1,25-dihydroxyvitamin D (the biologically active form of vitamin D), which reduces the absorption of calcium from the gastrointestinal tract, thereby stimulating the secretion of parathyroid hormone (PTH). In the conducted studies, it was found that SGLT2 inhibitors increase the concentration of serum phosphorus, FGF23 in the plasma and PTH in the plasma, while lowering the level of 1,25-dihydroxyvitamin D.
Detailed description
The study will be prospective, interventional and will be conducted in two parallel groups selected on the basis of clinical diagnosis. It is planned to enroll 60 patients aged 18-70 years under outpatient nephrological care, with impaired excretory function of the kidneys (eGFR 20-60 ml / min / 1.73 m3), with proteinuria above 0.5-3 g / l in the morning urine sample , including 30 nondiabetic and 30 diabetic patients t.2 and 20 healthy control subjects (no microalbuminuria and no impaired renal function with eGFR> 90 ml / min / 1.73m3). After the patients are familiarized with the objectives of the study and the informed consent signed, the following procedures will be performed.
After signing the consent, basic biochemical tests will be performed in both groups to assess the concentration of protein, albumin, calcium, phosphate, adenosine and creatinine in the morning urine sample, creatinine, calcium, phosphate, PTH, bacterial alkaline phosphatase (BAP), 1.25 vitamin D, sclerostins, FGF23, serum Klotho proteins, eGFR, plasma glucose. The tests will be repeated after 7 days of taking empagliflozin in a dose of 10 mg a day. On days 1 and 7, patients will be given an intravenous glucose 5% solution at a dose of 240 mg glucose / kg body weight in the first 15 minutes to induce a controlled hyperglycaemia state in the first 15 minutes, this will increase their blood glucose by 125 mg / dL in 15 minutes followed by 10-12 mg glucose / kg body weight, under glycemic control to maintain a concentration of 200 mg / dL ± 5% for 120 minutes. Stability of serum glucose levels during this period will be maintained by adjusting the rate of intravenous glucose infusion based on blood glucose measurements, every 15 minutes. After 2 hours of infusion, additional blood will be drawn for the determination of glucose and renal parameters and after 100 ml of urine for determination. adenosine, albumin and creatinine concentrations. In healthy subjects from the control group, the above basic blood and urine biochemical tests will be performed once.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study will be prospective, interventional and will be conducted in two parallel groups selected on the basis of clinical diagnosis (diabetic nephropathy or other chronic nephropathies).
| Arm | Type | Receives |
|---|---|---|
| diabetes group | Other | Drug: Empagliflozin 10 MGAfter qualifying for the study subjects with diabetes and chornic kidney disease received oral empagliflozin 10 mg once daily for 7 days. |
| non-diabetes group | Other | Drug: Empagliflozin 10 MGAfter qualifying for the study subjects with chronic kidney disease without diabetes received oral empagliflozin 10 mg once daily for 7 days. |
| control | Other | Drug: Empagliflozin 10 MGAfter qualifying for the study healthy subjects received oral empagliflozin 10 mg once daily for 7 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- type 2 diabetes complicated by diabetic nephropathy (first group), non-diabetic nephropathy (second group) or healthy subjects
- Angiotensin-converting enzyme inhibitor or antagonists of angiotensin receptor blockers in the stable dose for the 4 months
- age 18 - 70 years
- stable clinical condition for the last 3 months
- GFR 25-60 ml / min / 1.73 m2
Key exclusion criteria (10 listed)
- diabetes mellitus other than t.2
- have taken SGLT2 inhibitors in the last 4 weeks or have ever had an intolerance to SGLT2 inhibitors in the past
- acute kidney damage
- systolic blood pressure <90 mmHg
- Cancer
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 |
|---|---|---|
| Empagliflozin 10 MGAlso: JardianceAfter qualifying for the study all subjects received oral empagliflozin 10 mg once daily for 7 days. | Drug | control, diabetes group, non-diabetes group |
Primary outcome
albuminuria
Time frame: 7 days
ratio of albumin to creatinine in urine in mg/g
serum calcium concentration
Time frame: 7 days
serum calcium level in mmol/l
urine calcium concentration
Time frame: 7 days
level of calcium in urine in mmol/l
urine adenosine
Time frame: 7 days
adenosine in urine in µmol/mmol creatinine
urine phosphorus concetration
Time frame: 7 days
serum phosphorus level in mmol/l
serum Fibroblast growth factor 23 concentration
Time frame: 7 days
serum Fibroblast growth factor 23 level in pg/ml
serum parathormone concentration
Time frame: 7 days
serum parathormone level in pg/ml
serum Klotho concentration
Time frame: 7 days
serum Klotho level in ng/ml
serum Bone alkaline phosphatase concentration
Time frame: 7 days
serum Bone alkaline phosphatase level in µg/l
serum 1,25(OH)2D concentration
Time frame: 7 days
serum 1,25(OH)2D level in pg/ml
serum sclerostin concentration
Time frame: 7 days
serum sclerostin level in pmol/l
urine phosphorus concetration
Time frame: 7 days
phosphorus in urine in mmol/l
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2021.
- 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. This study is not recruiting at the moment.
Ireneusz Staroń study chair
Medical University of Lodz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Empagliflozin 10 MG in people with Chronic Kidney Disease stage3, run by Medical University of Lodz at 1 site in Poland.
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 6 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 14 Jul 2021. 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 Poland. 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?
Contact Michał Nowicki, Prof (+48 42 201 4400, nefro@wp.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
albuminuria (time frame: 7 days). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2021.