Diabetic NephropathyPhase 2NCT01493050
The Effects of Sevelamer Carbonate on Diabetic Nephropathy
A Phase 2 study testing Sevelamer Carbonate and calcium carbonate in people with Diabetic Nephropathy, run by Gary Striker at 2 sites in United States.
Trial summary
The purpose of this study is to see if taking a medication can lower the amount of oxidants from food that go into our body. Previous research shows that if the investigators lower the oxidants from food in people with diabetes, this simple change lowers different risks for heart disease and the worsening of kidney… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Nephropathy
- What is being tested?
- Sevelamer Carbonate and calcium carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2012to Dec 2013
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Evidence of CKD Stages II, III or IV
- Stage II CKD; eGFR 60-89 ml/min
- Stage III CKD: eGFR 30-59 ml/min
- Stage IV CKD: eGFR 15-29 ml/min
- Proteinuria (>200 mg/day or 300 mg/gm creatinine on a spot urine) on urinalysis on two occasions within 18 months of recruitment
- Diagnosis of diabetes and receiving at least one medication for diabetes mellitus
- HbA1c>6.5%
Who cannot join
- Age <18
- Patients receiving active treatment for hyperphosphatemia
- Biopsy proven renal disease other than diabetic nephropathy
- Hypophosphatemia
- Hypercalcemia
- Any history of significant gastrointestinal disorders
- Any history of significant gastrointestinal surgery such as ileostomy, colostomy and colectomy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beth Israel Medical Center
New York, New York, 10003
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Multi-Center Study of the Effect of Sevelamer Carbonate (Renvela®) on Metabolic/Inflammatory/ROS in Diabetics With Nephropathy
The purpose of this study is to see if taking a medication can lower the amount of oxidants from food that go into our body. Previous research shows that if the investigators lower the oxidants from food in people with diabetes, this simple change lowers different risks for heart disease and the worsening of kidney disease. The investigators focus on a specific type of oxidant, advanced glycation endproducts (AGEs). A previous, smaller study, conducted by our group showed that a drug, already approved by the FDA, will lower AGEs in the investigators compared Renvela® to Tums®. Both of these drugs have few side effects and have been used for a long time in patients with diabetes and kidney disease. While our previous study was interesting, it was just too small to be able to be sure that it will help all people with diabetes, or if the good effects the investigators found were simply due to chance. The investigators are doing this new study to confirm or deny the possibility that Renvela® can really help people with diabetes and kidney disease.
Read the detailed description
Advanced glycation end products (AGEs) levels are elevated in diabetic patients and in patients with chronic kidney disease (CKD) and may contribute to the excessive cardiovascular disease in this population, by promoting oxidant stress and chronic vascular inflammation. It has recently been recognized that AGEs in the body originate not only endogenously, but also from the ingestion of preformed AGEs in the diet. We have shown that reduction of dietary AGE intake leads to significant reductions of circulating AGEs and insulin levels as well as levels of markers of oxidative stress and inflammation in both diabetic and CKD patients. Thus, the increased inflammation and oxidative stress (Infl/OS) in stable diabetes mellitus (DM) are largely due to advanced glycation end products (AGEs) from food, and restricting AGEs-intake reduces these risk factors in DM. High circulating AGEs and TNFR1/2 have been shown to be associated with progression in diabetic nephropathy. Ideally, a compound that binds food AGEs within the lumen of the intestine should have the same effect as dietary restriction of AGEs and could become an important therapeutic tool in the clinical care of these patients. We found that Sevelamer binds AGEs in vitro in a pH dependent manner. This led us to hypothesize that sevelamer carbonate, but not calcium carbonate, would sequester AGEs in the gut and reduce Infl/OS, including circulating AGEs and TNFα, in T2DM with Stage 2-4 CKD. This hypothesis was tested in a Pilot Study (GCO-08-0976) we designed as a proof-of-concept trial to determine if a larger and longer trial is indicated. We conducted a randomized, open-label, intention-to-treat, two-month crossover study to compare stable diabetic patients with stage 2-4 CKD treated with either Sevelamer carbonate or calcium carbonate for 2 months, a 1 week wash-out, and then the opposite drug for 2 months. There were no changes in medications and food intake. We found that urinary phosphate excretion was decreased by both Sevelamer carbonate and calcium carbonate. Serum AGEs, lipids, HbA1c, FGF23, and 8-isoprostanes were reduced by Sevelamer carbonate compared to calcium carbonate. In addition, PMNC levels of AGER1, SIRT1 and TNFα were also decreased by Sevelamer carbonate, compared to calcium carbonate. We concluded that Sevelamer carbonate reduces HbA1c, FGF23, lipids, and TNFα via reduced inflammation and OS in stage 2-4 diabetic CKD. These changes were not seen with calcium carbonate. Since we found that sevelamer carbonate bound AGE-BSA (but not BSA) at pH 7.0, but not at pH 1.0 in vitro, we proposed that the mechanism action is sequestration of dietary AGEs and GI elimination. Based on these data, we concluded that a larger and longer trial is indicated to confirm these results.
The current study proposes to confirm that Sevelamer Carbonate, an agent known to prevent the gastrointestinal absorption of phosphates, is also able to block the absorption of AGEs and improve certain aspects of diabetes and chronic renal disease in a larger group of patients who will be followed for a longer period of time.
- Conditions
- Diabetic Nephropathy
- Being tested
- Sevelamer Carbonate, calcium carbonate
- Keywords
- Diabetic Nephropathy, Sevelamer Carbonate
- Medical subject headings
- Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sevelamer CarbonateDrug
1600 mg (two 800 mg in the form of tablets or powder to be diluted in water) TID with meals for 26 weeks
calcium carbonateDrug
Also called (Tums®)
1200 mg of calcium carbonate TID with meals for 26 weeks
| Study group | Role | What they receive |
|---|---|---|
| Sevelamer Carbonate | Experimental | 1600 mg (two 800 mg in the form of tablets or powder to be diluted in water) TID with meals for 26 weeks Receives: Drug: Sevelamer Carbonate |
| calcium carbonate | Active comparator | 1200 mg of calcium carbonate TID with meals for 26 weeks Receives: Drug: calcium carbonate |
What is being measured
The primary outcome is the main question the study is designed to answer.
glucose metabolism
HbA1C and serum AGE levels
Measured: baseline
glucose metabolism
HbA1C and serum AGE levels
Measured: at 3 months
glucose metabolism
HbA1C and serum AGE levels
Measured: at 6 months
Secondary outcomes (8)
markers of inflammation and oxidative stress
Measured: baseline
markers of inflammation and oxidative stress
Measured: at 3 months
markers of inflammation and oxidative stress
Measured: at 6 months
serum lipid levels
Measured: baseline
serum lipid levels
Measured: at 3 months
serum lipid levels
Measured: at 6 months
serum phosphate level
to check for hypophosphatemia
Measured: at one week
serum phosphate level
to check for hypophosphatemia
Measured: at two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2011 (estimated)
- Study startFeb 2012
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetic NephropathyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gary Striker
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gary Striker, Icahn School of Medicine at Mount Sinai
- Investigators
- Gary Striker, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01493050
- Sponsor's protocol ID
- GCO 11-0973
- Status last verified
- Apr 2014
- First submitted
- 13 Dec 2011
- Last updated
- 9 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.
PubMed 40576086Vlassara H, Uribarri J, Cai W, Goodman S, Pyzik R, Post J, Grosjean F, Woodward M, Striker GE. Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol. 2012 Jun;7(6):934-42. doi: 10.2215/CJN.12891211. Epub 2012 Mar 29.
PubMed 22461535
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Center Study of the Effect of Sevelamer Carbonate (Renvela®) on Metabolic/Inflammatory/ROS in Diabetics With Nephropathy
- ClinicalTrials.gov ID
- NCT01493050
- Acronym / sponsor ID
- GCO 11-0973
- Conditions
- Diabetic Nephropathy
- Keywords
- Diabetic Nephropathy, Sevelamer Carbonate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Gary StrikerUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 15 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if taking a medication can lower the amount of oxidants from food that go into our body. Previous research shows that if the investigators lower the oxidants from food in people with diabetes, this simple change lowers different risks for heart disease and the worsening of kidney disease. The investigators focus on a specific type of oxidant, advanced glycation endproducts (AGEs). A previous, smaller study, conducted by our group showed that a drug, already approved by the FDA, will lower AGEs in the investigators compared Renvela® to Tums®. Both of these drugs have few side effects and have been used for a long time in patients with diabetes and kidney disease. While our previous study was interesting, it was just too small to be able to be sure that it will help all people with diabetes, or if the good effects the investigators found were simply due to chance. The investigators are doing this new study to confirm or deny the possibility that Renvela® can really help people with diabetes and kidney disease.
Detailed description
Advanced glycation end products (AGEs) levels are elevated in diabetic patients and in patients with chronic kidney disease (CKD) and may contribute to the excessive cardiovascular disease in this population, by promoting oxidant stress and chronic vascular inflammation. It has recently been recognized that AGEs in the body originate not only endogenously, but also from the ingestion of preformed AGEs in the diet. We have shown that reduction of dietary AGE intake leads to significant reductions of circulating AGEs and insulin levels as well as levels of markers of oxidative stress and inflammation in both diabetic and CKD patients. Thus, the increased inflammation and oxidative stress (Infl/OS) in stable diabetes mellitus (DM) are largely due to advanced glycation end products (AGEs) from food, and restricting AGEs-intake reduces these risk factors in DM. High circulating AGEs and TNFR1/2 have been shown to be associated with progression in diabetic nephropathy. Ideally, a compound that binds food AGEs within the lumen of the intestine should have the same effect as dietary restriction of AGEs and could become an important therapeutic tool in the clinical care of these patients. We found that Sevelamer binds AGEs in vitro in a pH dependent manner. This led us to hypothesize that sevelamer carbonate, but not calcium carbonate, would sequester AGEs in the gut and reduce Infl/OS, including circulating AGEs and TNFα, in T2DM with Stage 2-4 CKD. This hypothesis was tested in a Pilot Study (GCO-08-0976) we designed as a proof-of-concept trial to determine if a larger and longer trial is indicated. We conducted a randomized, open-label, intention-to-treat, two-month crossover study to compare stable diabetic patients with stage 2-4 CKD treated with either Sevelamer carbonate or calcium carbonate for 2 months, a 1 week wash-out, and then the opposite drug for 2 months. There were no changes in medications and food intake. We found that urinary phosphate excretion was decreased by both Sevelamer carbonate and calcium carbonate. Serum AGEs, lipids, HbA1c, FGF23, and 8-isoprostanes were reduced by Sevelamer carbonate compared to calcium carbonate. In addition, PMNC levels of AGER1, SIRT1 and TNFα were also decreased by Sevelamer carbonate, compared to calcium carbonate. We concluded that Sevelamer carbonate reduces HbA1c, FGF23, lipids, and TNFα via reduced inflammation and OS in stage 2-4 diabetic CKD. These changes were not seen with calcium carbonate. Since we found that sevelamer carbonate bound AGE-BSA (but not BSA) at pH 7.0, but not at pH 1.0 in vitro, we proposed that the mechanism action is sequestration of dietary AGEs and GI elimination. Based on these data, we concluded that a larger and longer trial is indicated to confirm these results.
The current study proposes to confirm that Sevelamer Carbonate, an agent known to prevent the gastrointestinal absorption of phosphates, is also able to block the absorption of AGEs and improve certain aspects of diabetes and chronic renal disease in a larger group of patients who will be followed for a longer period of time.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sevelamer Carbonate | Experimental | Drug: Sevelamer Carbonate1600 mg (two 800 mg in the form of tablets or powder to be diluted in water) TID with meals for 26 weeks |
| calcium carbonate | Active comparator | Drug: calcium carbonate1200 mg of calcium carbonate TID with meals for 26 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age > 18 years
- Evidence of CKD Stages II, III or IV
- Stage II CKD; eGFR 60-89 ml/min
- Stage III CKD: eGFR 30-59 ml/min
- Stage IV CKD: eGFR 15-29 ml/min
Key exclusion criteria (7 listed)
- Age <18
- Patients receiving active treatment for hyperphosphatemia
- Biopsy proven renal disease other than diabetic nephropathy
- Hypophosphatemia
- Hypercalcemia
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 |
|---|---|---|
| Sevelamer Carbonate1600 mg (two 800 mg in the form of tablets or powder to be diluted in water) TID with meals for 26 weeks | Drug | Sevelamer Carbonate |
| calcium carbonateAlso: (Tums®)1200 mg of calcium carbonate TID with meals for 26 weeks | Drug | calcium carbonate |
Primary outcome
glucose metabolism
Time frame: baseline
HbA1C and serum AGE levels
glucose metabolism
Time frame: at 3 months
HbA1C and serum AGE levels
glucose metabolism
Time frame: at 6 months
HbA1C and serum AGE levels
8 secondary outcomes
markers of inflammation and oxidative stress
Time frame: baseline
markers of inflammation and oxidative stress
Time frame: at 3 months
markers of inflammation and oxidative stress
Time frame: at 6 months
serum lipid levels
Time frame: baseline
serum lipid levels
Time frame: at 3 months
serum lipid levels
Time frame: at 6 months
serum phosphate level
Time frame: at one week
serum phosphate level
Time frame: at two weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2014.
- Derived from this study: PubMed 40576086Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.
- Derived from this study: PubMed 22461535Vlassara H, Uribarri J, Cai W, Goodman S, Pyzik R, Post J, Grosjean F, Woodward M, Striker GE. Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol. 2012 Jun;7(6):934-42. doi: 10.2215/CJN.12891211. Epub 2012 Mar 29.
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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.
Gary Striker, MD principal investigator
Icahn School of Medicine at Mount Sinai
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sevelamer Carbonate and calcium carbonate in people with Diabetic Nephropathy, run by Gary Striker at 2 sites in United States.
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 8 inclusion and 7 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: finished, as of the sponsor's last update on 9 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
glucose metabolism (time frame: baseline). 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 NCT01493050, which also lists 2 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 9 Apr 2014.