HyperparathyroidismPhase 3NCT01191762
Sevelamer and Secondary Hyperparathyroidism in Chronic Kidney Disease
A Phase 3 study testing sevelamer carbonate in people with Hyperparathyroidism and Chronic Kidney Disease, run by Kenneth R. Phelps, M.D. at 1 site in United States.
Trial summary
The hypothesis underlying this study is that phosphate interferes with PTH-mediated calcium reabsorption in the distal nephron and thereby necessitates supranormal [PTH]to maintain normocalcemia in chronic kidney disease. Read more about this study
- Who is it for?
- Ages 18 to 120 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperparathyroidism, Chronic Kidney Disease
- What is being tested?
- sevelamer carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Apr 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 120 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- eGFR < 60 ml/min
- age at least 18 years
Who cannot join
- any primary parathyroid disease
Trial locations and contacts
1 site in 1 country.
United States1 site
Stratton Veterans Affairs Medical Center
Albany, New York, 12208
About this study
Official title: The Effect of Sevelamer Carbonate on Critical Variables in the Pathogenesis of Secondary Hyperparathyroidism
The hypothesis underlying this study is that phosphate interferes with PTH-mediated calcium reabsorption in the distal nephron and thereby necessitates supranormal [PTH]to maintain normocalcemia in chronic kidney disease. This study will examine the hypothesis with measures of phosphate homeostasis and calcium reabsorption. A double-blind trial of the intestinal phosphate binder sevelamer carbonate will be employed to examine whether reductions in phosphate influx alter distal nephron phosphate concentration and the [PTH] required for calcium reabsorption in the expected manner.
Read the detailed description
The parathyroid hormone concentration ([PTH)] rises as glomerular filtration rate (GFR) falls. This almost universal phenomenon is called secondary hyperparathyroidism (SHPT). [PTH] rises with dietary phosphate in chronic kidney disease. [PTH] also rises with stable dietary phosphate as GFR falls. The mechanism underlying these phenomena is unknown.
We hypothesize that phosphate exerts its effect on [PTH] in the cortical distal nephron (CDN). Ordinarily, intestinal phosphate absorption does not fall in proportion to GFR as chronic kidney disease (CKD) progresses. Consequently, the concentration of phosphate increases in the cortical distal nephron (CDN), where PTH regulates tubular calcium reabsorption. We speculate that increased [P]cdn reduces the concentration of free calcium through complexation, and thereby necessitates high [PTH] for achievement of calcium reabsorption sufficient to maintain normocalcemia. We can show algebraically that [P]cdn is proportional to the ratio EP/Ccr, where EP is the urinary excretion rate of phosphate and Ccr is creatinine clearance, a surrogate for GFR. EP/Ccr can be calculated from measurements in aliquots of serum and urine as [P]u[cr]s/[cr]u. If our hypothesis is correct, we anticipate that [PTH] will be proportional to EP/Ccr in CKD, and that delta [PTH] will be proportional to delta EP/Ccr obtained with sequential determinations.
We will study 30 patients with CKD and a comparable number of controls. All subjects will have normocalcemia. Controls will be seen once for informed consent, and once in the fasting state between 8:00 a.m. and 10:00 a.m. for collection of urine and blood specimens.
Patients with CKD will be seen at five visits at intervals of four weeks. At the first visit, we will obtain informed consent and obtain a specimen for measurement of 25-hydroxyvitamin D (25OHD). At visits 2-5, we will obtain necessary specimens to measure concentrations of PTH, fibroblast growth factor 23 (FGF23), 25OHD, and 1,25-dihyroxyvitamin D (1,25(OH)2D). We will also measure ionized and ultrafilterable calcium, creatinine, and phosphorus in serum and calcium, phosphorus, and creatinine in urine. These measurements will enable us to follow the effects of interventions on hormone concentrations and parameters of calcium and phosphorus homeostasis.
At visit 2 we will prescribe vitamin D in accordance with [25OHD] obtained at visit 1. For [25OHD] < 32 ng/mL, doses will be 50,000 units/d of D2 for one week, followed by 2000 mg/d of D2 for 3 weeks. For [25OHD] > 32 ng/mL, the dose will be D3 2000 mg/d for four weeks. The purpose of this intervention is to minimize the likelihood that vitamin D insufficiency or deficiency contributes to SHPT.
At visit 3, we will instruct patients in a phosphate-restricted diet. At visit 4 we will quantify the metabolic effects of the diet, and will randomly assign patients to receive either placebo or sevelamer carbonate 800 mg tablets, 3 with each meal. At visit 5, we will quantify the effects of the two interventions on parameters of calcium and phosphate homeostasis and on hormone concentrations. We will view positive regressions of [PTH] on EP/Ccr and of ∆[PTH] on ∆EP/Ccr as evidence for our hypothesis.
- Conditions
- Hyperparathyroidism, Chronic Kidney Disease
- Being tested
- sevelamer carbonate, placebo
- Keywords
- secondary hyperparathyroidism, phosphate, calcium, chronic kidney disease
- Medical subject headings
- Hyperparathyroidism, Renal Insufficiency, Chronic, Hyperparathyroidism, Secondary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sevelamer carbonateDrug
Also called Renvela (Genzyme)
2400 mg with each meal for 4 weeks
placeboDrug
3 tablets with each meal
| Study group | Role | What they receive |
|---|---|---|
| sevelamer carbonate | Active comparator | 2400 mg (3 pills) with each meal Receives: Drug: sevelamer carbonate |
| placebo control | Placebo comparator | 3 placebo tablets with each meal; tablets are identical to sevelamer carbonate 800 mg tablets. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fractional Change in [PTH] in CKD After a 4-week Course of Sevelamer Carbonate
This outcome measure documented the effect of intestinal phosphate-binding on [PTH]. Fractional change was calculated as ([PTH]post - [PTH]pre)/[PTH]pre, where 'pre' and 'post' referred respectively to baseline [PTH] (before treatment) and [PTH] after four weeks of treatment. Reductions were cited as negative numbers, and increments were cited as positive numbers.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2010 (estimated)
- Study startApr 2010
- Primary completionAug 2012
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HyperparathyroidismStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kenneth R. Phelps, M.D.
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor-investigator, Kenneth R. Phelps, M.D., Phelps, Kenneth R., M.D.
- Investigators
- Kenneth R. Phelps, M.D., Principal investigator, Stratton VAMC, Albany, NY
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01191762
- Sponsor's protocol ID
- PhelpsK
- Status last verified
- Sep 2016
- First submitted
- 27 Aug 2010
- Last updated
- 1 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
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 40576086Phelps KR, Mason DL. Parathyroid Hormone, Fibroblast Growth Factor 23, and Parameters of Phosphate Reabsorption. Am J Nephrol. 2018;47(5):343-351. doi: 10.1159/000489270. Epub 2018 May 18.
PubMed 29779023Phelps KR, Mason DL, Stote KS. Phosphate homeostasis, parathyroid hormone, and fibroblast growth factor 23 in stages 3 and 4 chronic kidney disease. Clin Nephrol. 2016 May;85(5):251-61. doi: 10.5414/CN108686.
PubMed 26951967Phelps KR, Mason DL. Parameters of phosphorus homeostasis at normal and reduced GFR: theoretical considerations. Clin Nephrol. 2015 Mar;83(3):167-76. doi: 10.5414/cn108367.
PubMed 25685872
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Sevelamer Carbonate on Critical Variables in the Pathogenesis of Secondary Hyperparathyroidism
- ClinicalTrials.gov ID
- NCT01191762
- Acronym / sponsor ID
- PhelpsK
- Conditions
- Hyperparathyroidism, Chronic Kidney Disease
- Keywords
- secondary hyperparathyroidism, phosphate, calcium, chronic kidney disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Kenneth R. Phelps, M.D.
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Apr 2010
- Primary completion
- Aug 2012 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 31 Aug 2010 (estimated)
- Results
- Posted 31 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hypothesis underlying this study is that phosphate interferes with PTH-mediated calcium reabsorption in the distal nephron and thereby necessitates supranormal [PTH]to maintain normocalcemia in chronic kidney disease. This study will examine the hypothesis with measures of phosphate homeostasis and calcium reabsorption. A double-blind trial of the intestinal phosphate binder sevelamer carbonate will be employed to examine whether reductions in phosphate influx alter distal nephron phosphate concentration and the [PTH] required for calcium reabsorption in the expected manner.
Detailed description
The parathyroid hormone concentration ([PTH)] rises as glomerular filtration rate (GFR) falls. This almost universal phenomenon is called secondary hyperparathyroidism (SHPT). [PTH] rises with dietary phosphate in chronic kidney disease. [PTH] also rises with stable dietary phosphate as GFR falls. The mechanism underlying these phenomena is unknown.
We hypothesize that phosphate exerts its effect on [PTH] in the cortical distal nephron (CDN). Ordinarily, intestinal phosphate absorption does not fall in proportion to GFR as chronic kidney disease (CKD) progresses. Consequently, the concentration of phosphate increases in the cortical distal nephron (CDN), where PTH regulates tubular calcium reabsorption. We speculate that increased [P]cdn reduces the concentration of free calcium through complexation, and thereby necessitates high [PTH] for achievement of calcium reabsorption sufficient to maintain normocalcemia. We can show algebraically that [P]cdn is proportional to the ratio EP/Ccr, where EP is the urinary excretion rate of phosphate and Ccr is creatinine clearance, a surrogate for GFR. EP/Ccr can be calculated from measurements in aliquots of serum and urine as [P]u[cr]s/[cr]u. If our hypothesis is correct, we anticipate that [PTH] will be proportional to EP/Ccr in CKD, and that delta [PTH] will be proportional to delta EP/Ccr obtained with sequential determinations.
We will study 30 patients with CKD and a comparable number of controls. All subjects will have normocalcemia. Controls will be seen once for informed consent, and once in the fasting state between 8:00 a.m. and 10:00 a.m. for collection of urine and blood specimens.
Patients with CKD will be seen at five visits at intervals of four weeks. At the first visit, we will obtain informed consent and obtain a specimen for measurement of 25-hydroxyvitamin D (25OHD). At visits 2-5, we will obtain necessary specimens to measure concentrations of PTH, fibroblast growth factor 23 (FGF23), 25OHD, and 1,25-dihyroxyvitamin D (1,25(OH)2D). We will also measure ionized and ultrafilterable calcium, creatinine, and phosphorus in serum and calcium, phosphorus, and creatinine in urine. These measurements will enable us to follow the effects of interventions on hormone concentrations and parameters of calcium and phosphorus homeostasis.
At visit 2 we will prescribe vitamin D in accordance with [25OHD] obtained at visit 1. For [25OHD] < 32 ng/mL, doses will be 50,000 units/d of D2 for one week, followed by 2000 mg/d of D2 for 3 weeks. For [25OHD] > 32 ng/mL, the dose will be D3 2000 mg/d for four weeks. The purpose of this intervention is to minimize the likelihood that vitamin D insufficiency or deficiency contributes to SHPT.
At visit 3, we will instruct patients in a phosphate-restricted diet. At visit 4 we will quantify the metabolic effects of the diet, and will randomly assign patients to receive either placebo or sevelamer carbonate 800 mg tablets, 3 with each meal. At visit 5, we will quantify the effects of the two interventions on parameters of calcium and phosphate homeostasis and on hormone concentrations. We will view positive regressions of [PTH] on EP/Ccr and of ∆[PTH] on ∆EP/Ccr as evidence for our hypothesis.
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 | Active comparator | Drug: sevelamer carbonate2400 mg (3 pills) with each meal |
| placebo control | Placebo comparator | Drug: placebo3 placebo tablets with each meal; tablets are identical to sevelamer carbonate 800 mg tablets. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- eGFR < 60 ml/min
- age at least 18 years
Key exclusion criteria (1 listed)
- any primary parathyroid disease
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 carbonateAlso: Renvela (Genzyme)2400 mg with each meal for 4 weeks | Drug | sevelamer carbonate |
| placebo3 tablets with each meal | Drug | placebo control |
Primary outcome
Fractional Change in [PTH] in CKD After a 4-week Course of Sevelamer Carbonate
Time frame: 4 weeks
This outcome measure documented the effect of intestinal phosphate-binding on [PTH]. Fractional change was calculated as ([PTH]post - [PTH]pre)/[PTH]pre, where 'pre' and 'post' referred respectively to baseline [PTH] (before treatment) and [PTH] after four weeks of treatment. Reductions were cited as negative numbers, and increments were cited as positive numbers.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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 29779023Phelps KR, Mason DL. Parathyroid Hormone, Fibroblast Growth Factor 23, and Parameters of Phosphate Reabsorption. Am J Nephrol. 2018;47(5):343-351. doi: 10.1159/000489270. Epub 2018 May 18.
- Derived from this study: PubMed 26951967Phelps KR, Mason DL, Stote KS. Phosphate homeostasis, parathyroid hormone, and fibroblast growth factor 23 in stages 3 and 4 chronic kidney disease. Clin Nephrol. 2016 May;85(5):251-61. doi: 10.5414/CN108686.
- Derived from this study: PubMed 25685872Phelps KR, Mason DL. Parameters of phosphorus homeostasis at normal and reduced GFR: theoretical considerations. Clin Nephrol. 2015 Mar;83(3):167-76. doi: 10.5414/cn108367.
- 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.
Kenneth R. Phelps, M.D. principal investigator
Stratton VAMC, Albany, NY
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing sevelamer carbonate in people with Hyperparathyroidism and Chronic Kidney Disease, run by Kenneth R. Phelps, M.D. at 1 site 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 2 inclusion and 1 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 1 Nov 2016. 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 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Fractional Change in [PTH] in CKD After a 4-week Course of Sevelamer Carbonate (time frame: 4 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 NCT01191762, which also lists 4 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 1 Nov 2016.