ProteinuriaPhase 4NCT02522650
A Crossover Pilot Study of the Effect of Amiloride on Proteinuria
A Phase 4 study testing Amiloride and Triamterene in people with Proteinuria, run by Georgetown University at 1 site in United States.
Trial summary
This cross-over study is designed to test the hypothesis that amiloride will reduce urinary protein excretion and protect the kidney from rapid progression in proteinuric kidney disease. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Proteinuria
- What is being tested?
- Amiloride and Triamterene
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Oct 2021
- Phase
- Phase 4
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient with any type of proteinuric kidney diseases
- Aged 18-75
- Proteinuria ≥1g/day
- estimated glomerular filtration rate (eGFR) ≥ 30ml/min/1.73m2
Who cannot join
- Clinical evidences of lupus nephritis, or HIV associated nephropathy
- eGFR <30ml/min/1.73m2
- Requirement for treatment with mineralocorticoid receptor antagonists (spironolactone, eplerenone)
- Status post kidney transplant
- Received glucocorticoid steroids within six months
- Serum K >4.8 mmol/L
Show all 10Show fewer
- Total carbon dioxide <17 mmol/L
- Hemoglobin <10 g/dl
- Contraindicated or allergic to loop diuretics or potassium sparing diuretics
- Abnormal liver function tests
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Georgetown University
Washington D.C., District of Columbia, 20007
Margie Dimatulac, 202-444-1210, mcd136@georgetown.edu.edu
MD, 202-444-1089
About this study
Official title: A Crossover Pilot Study of the Effect of Amiloride on Proteinuria in Patients With Proteinuric Kidney Disease
This cross-over study is designed to test the hypothesis that amiloride will reduce urinary protein excretion and protect the kidney from rapid progression in proteinuric kidney disease.
Read the detailed description
Patients with proteinuric kidney disease will be enrolled and receive either amiloride or triamterene first, a similar diuretic acting on epithelial sodium channel (ENaC) as amiloride, but not inhibiting urokinase plasminogen activator receptor (uPAR), will be used as a control. Then patients will cross over to receive another medication. We postulate that amiloride could be beneficial in the patients with proteinuric kidney diseases and could be used as an adjunct therapy to reduce proteinuria and to delay renal disease progression in this patient population.
Specific Aim 1: To examine the effects of amiloride on 24 hour urine protein excretion in patients with proteinuric kidney diseases.
Specific Aim 2: To study if the effect of amiloride on proteinuria reduction is mediated by suppressing soluble urokinase plasminogen activator receptor (suPAR) expression.
Study Design:
The study includes 3 phases. 30 patients will be recruited to this study. All patients need to be on an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) daily at least two month prior to the study.
Phase 1: Patients will be randomized to receive either amiloride 5mg twice daily or triamterene 50mg twice daily for 8 weeks. Serum potassium will be monitored one week before and one week after starting phase 1. If serum potassium remains equal to or less than 5.0mmol/L, amiloride or triamterene will be continued at same dose until the end of phase 1. If serum potassium is equal to or above 5.5 mmol/L, the patient will exit the study, and an adverse event will be reported. If serum potassium is between 5.1-5.4 mmol/L, it will be monitored again in one week. If serum potassium is above 5.5 mmol/L, the patient will exit the study, and an adverse event will be reported. If serum potassium remains in the same range, the patient will continue amiloride or triamterene at the same dose to complete phase 1.
Phase 2: the patients will discontinue amiloride or triamterene for a washout for 4 weeks, but continue with the ACE inhibitor or ARB.
Phase 3: the patients will cross over to triamterene or amiloride for 8 weeks. Use the protocol as described in phase 1.
- Conditions
- Proteinuria
- Being tested
- Amiloride, Triamterene
- Keywords
- amiloride, proteinuric kidney disease, urokinase plasminogen activator receptor, proteinuria
- Medical subject headings
- Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmilorideDrug
5mg twice a day for 8 weeks
TriamtereneDrug
50mg twice a day for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Amiloride Phase | Experimental | Subject receives 5mg of Amiloride twice daily for 8 weeks. Receives: Drug: Amiloride |
| Triamterene Phase | Active comparator | Subject receives 50mg of Triamterene twice daily for 8 weeks. Receives: Drug: Triamterene |
| Washout Phase | No intervention | Subject does not take any study medication for 4 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
24 hr urine protein excretion
Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.
Measured: 20 weeks
Secondary outcomes (4)
urine plasmin activity
examine urine plasmin activity during the 3 phases of the study. Serum and urine plasmin will be measured by gelatin-PAGE zymography.
Measured: 20 weeks
urine plasminogen activity
examine urine plasminogen activity during the 3 phases of the study. urine plasminogen will be measured by gelatin-PAGE zymography.
Measured: 20 weeks
urine suPAR concentration
examine urine suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.
Measured: 20 weeks
serum suPAR concentration
examine serum suPAR concentration during the 3 phases of the study. suPAR concentration will be measured by ELISA kit.
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2015 (estimated)
- Study startJul 2013
- Primary completionOct 2021 (estimated)
- Study completionOct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (31)Papers the sponsor has linked to this study.
- Other trials for ProteinuriaStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wen Shen, MD, PHD, Georgetown University
- Investigators
- Wen Shen, MD, PhD, Principal investigator, Georgetown University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02522650
- Sponsor's protocol ID
- 2013-0496
- Status last verified
- Feb 2020
- First submitted
- 23 Jul 2015
- Last updated
- 7 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Berhane AM, Weil EJ, Knowler WC, Nelson RG, Hanson RL. Albuminuria and estimated glomerular filtration rate as predictors of diabetic end-stage renal disease and death. Clin J Am Soc Nephrol. 2011 Oct;6(10):2444-51. doi: 10.2215/CJN.00580111. Epub 2011 Aug 18.
PubMed 21852671Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002 Dec;3(12):932-43. doi: 10.1038/nrm977.
PubMed 12461559Brown EA, Markandu ND, Roulston JE, Jones BE, Squires M, MacGregor GA. Is the renin-angiotensin-aldosterone system involved in the sodium retention in the nephrotic syndrome? Nephron. 1982;32(2):102-7. doi: 10.1159/000182827.
PubMed 6757778Brown EA, Markandu ND, Sagnella GA, Jones BE, MacGregor GA. Lack of effect of captopril on the sodium retention of the nephrotic syndrome. Nephron. 1984;37(1):43-8. doi: 10.1159/000183206.
PubMed 6371561Busch AE, Suessbrich H, Kunzelmann K, Hipper A, Greger R, Waldegger S, Mutschler E, Lindemann B, Lang F. Blockade of epithelial Na+ channels by triamterenes - underlying mechanisms and molecular basis. Pflugers Arch. 1996 Sep;432(5):760-6. doi: 10.1007/s004240050196.
PubMed 8772124Geers AB, Koomans HA, Roos JC, Boer P, Dorhout Mees EJ. Functional relationships in the nephrotic syndrome. Kidney Int. 1984 Sep;26(3):324-30. doi: 10.1038/ki.1984.176.
PubMed 6392692Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997 Jun 28;349(9069):1857-63.
PubMed 9217756Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR, Wiebe N, Tonelli M; Alberta Kidney Disease Network. Relation between kidney function, proteinuria, and adverse outcomes. JAMA. 2010 Feb 3;303(5):423-9. doi: 10.1001/jama.2010.39.
PubMed 20124537Iishi H, Tatsuta M, Baba M, Yano H, Uehara H, Nakaizumi A. Suppression by amiloride of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane. Int J Cancer. 1995 Nov 27;63(5):716-9. doi: 10.1002/ijc.2910630518.
PubMed 7591290Kellen JA, Mirakian A, Kolin A. Antimetastatic effect of amiloride in an animal tumour model. Anticancer Res. 1988 Nov-Dec;8(6):1373-6.
PubMed 3218971Laurens WE, Vanrenterghem YF, Steels PS, Van Damme BJ. A new single nephron model of focal and segmental glomerulosclerosis in the Munich-Wistar rat. Kidney Int. 1994 Jan;45(1):143-9. doi: 10.1038/ki.1994.17.
PubMed 8127003Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993 Nov 11;329(20):1456-62. doi: 10.1056/NEJM199311113292004.
PubMed 8413456Madsen CD, Ferraris GM, Andolfo A, Cunningham O, Sidenius N. uPAR-induced cell adhesion and migration: vitronectin provides the key. J Cell Biol. 2007 Jun 4;177(5):927-39. doi: 10.1083/jcb.200612058.
PubMed 17548516Mathieson PW. Proteinuria and immunity--an overstated relationship? N Engl J Med. 2008 Dec 4;359(23):2492-4. doi: 10.1056/NEJMcibr0806881. No abstract available.
PubMed 19052132Meltzer JI, Keim HJ, Laragh JH, Sealey JE, Jan KM, Chien S. Nephrotic syndrome: vasoconstriction and hypervolemic types indicated by renin-sodium profiling. Ann Intern Med. 1979 Nov;91(5):688-96. doi: 10.7326/0003-4819-91-5-688.
PubMed 496101
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Crossover Pilot Study of the Effect of Amiloride on Proteinuria in Patients With Proteinuric Kidney Disease
- ClinicalTrials.gov ID
- NCT02522650
- Acronym / sponsor ID
- 2013-0496
- Conditions
- Proteinuria
- Keywords
- amiloride, proteinuric kidney disease, urokinase plasminogen activator receptor, proteinuria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Oct 2021 (estimated)
- First posted
- 13 Aug 2015 (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.
This cross-over study is designed to test the hypothesis that amiloride will reduce urinary protein excretion and protect the kidney from rapid progression in proteinuric kidney disease.
Detailed description
Patients with proteinuric kidney disease will be enrolled and receive either amiloride or triamterene first, a similar diuretic acting on epithelial sodium channel (ENaC) as amiloride, but not inhibiting urokinase plasminogen activator receptor (uPAR), will be used as a control. Then patients will cross over to receive another medication. We postulate that amiloride could be beneficial in the patients with proteinuric kidney diseases and could be used as an adjunct therapy to reduce proteinuria and to delay renal disease progression in this patient population.
Specific Aim 1: To examine the effects of amiloride on 24 hour urine protein excretion in patients with proteinuric kidney diseases.
Specific Aim 2: To study if the effect of amiloride on proteinuria reduction is mediated by suppressing soluble urokinase plasminogen activator receptor (suPAR) expression.
Study Design:
The study includes 3 phases. 30 patients will be recruited to this study. All patients need to be on an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) daily at least two month prior to the study.
Phase 1: Patients will be randomized to receive either amiloride 5mg twice daily or triamterene 50mg twice daily for 8 weeks. Serum potassium will be monitored one week before and one week after starting phase 1. If serum potassium remains equal to or less than 5.0mmol/L, amiloride or triamterene will be continued at same dose until the end of phase 1. If serum potassium is equal to or above 5.5 mmol/L, the patient will exit the study, and an adverse event will be reported. If serum potassium is between 5.1-5.4 mmol/L, it will be monitored again in one week. If serum potassium is above 5.5 mmol/L, the patient will exit the study, and an adverse event will be reported. If serum potassium remains in the same range, the patient will continue amiloride or triamterene at the same dose to complete phase 1.
Phase 2: the patients will discontinue amiloride or triamterene for a washout for 4 weeks, but continue with the ACE inhibitor or ARB.
Phase 3: the patients will cross over to triamterene or amiloride for 8 weeks. Use the protocol as described in phase 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Amiloride Phase | Experimental | Drug: AmilorideSubject receives 5mg of Amiloride twice daily for 8 weeks. |
| Triamterene Phase | Active comparator | Drug: TriamtereneSubject receives 50mg of Triamterene twice daily for 8 weeks. |
| Washout Phase | No intervention | –Subject does not take any study medication for 4 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patient with any type of proteinuric kidney diseases
- Aged 18-75
- Proteinuria ≥1g/day
- estimated glomerular filtration rate (eGFR) ≥ 30ml/min/1.73m2
Key exclusion criteria (10 listed)
- Clinical evidences of lupus nephritis, or HIV associated nephropathy
- eGFR <30ml/min/1.73m2
- Requirement for treatment with mineralocorticoid receptor antagonists (spironolactone, eplerenone)
- Status post kidney transplant
- Received glucocorticoid steroids within six months
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 |
|---|---|---|
| Amiloride5mg twice a day for 8 weeks | Drug | Amiloride Phase |
| Triamterene50mg twice a day for 8 weeks | Drug | Triamterene Phase |
Primary outcome
24 hr urine protein excretion
Time frame: 20 weeks
Identify changes in 24 hr urine protein excretion throughout the 3 phases of the study.
4 secondary outcomes
urine plasmin activity
Time frame: 20 weeks
urine plasminogen activity
Time frame: 20 weeks
urine suPAR concentration
Time frame: 20 weeks
serum suPAR concentration
Time frame: 20 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2020.
- Background: PubMed 21852671Berhane AM, Weil EJ, Knowler WC, Nelson RG, Hanson RL. Albuminuria and estimated glomerular filtration rate as predictors of diabetic end-stage renal disease and death. Clin J Am Soc Nephrol. 2011 Oct;6(10):2444-51. doi: 10.2215/CJN.00580111. Epub 2011 Aug 18.
- Background: PubMed 12461559Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002 Dec;3(12):932-43. doi: 10.1038/nrm977.
- Background: PubMed 6757778Brown EA, Markandu ND, Roulston JE, Jones BE, Squires M, MacGregor GA. Is the renin-angiotensin-aldosterone system involved in the sodium retention in the nephrotic syndrome? Nephron. 1982;32(2):102-7. doi: 10.1159/000182827.
- Background: PubMed 6371561Brown EA, Markandu ND, Sagnella GA, Jones BE, MacGregor GA. Lack of effect of captopril on the sodium retention of the nephrotic syndrome. Nephron. 1984;37(1):43-8. doi: 10.1159/000183206.
- Background: PubMed 8772124Busch AE, Suessbrich H, Kunzelmann K, Hipper A, Greger R, Waldegger S, Mutschler E, Lindemann B, Lang F. Blockade of epithelial Na+ channels by triamterenes - underlying mechanisms and molecular basis. Pflugers Arch. 1996 Sep;432(5):760-6. doi: 10.1007/s004240050196.
- Background: PubMed 6392692Geers AB, Koomans HA, Roos JC, Boer P, Dorhout Mees EJ. Functional relationships in the nephrotic syndrome. Kidney Int. 1984 Sep;26(3):324-30. doi: 10.1038/ki.1984.176.
- Background: PubMed 9217756Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997 Jun 28;349(9069):1857-63.
- Background: PubMed 20124537Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR, Wiebe N, Tonelli M; Alberta Kidney Disease Network. Relation between kidney function, proteinuria, and adverse outcomes. JAMA. 2010 Feb 3;303(5):423-9. doi: 10.1001/jama.2010.39.
- Background: PubMed 7591290Iishi H, Tatsuta M, Baba M, Yano H, Uehara H, Nakaizumi A. Suppression by amiloride of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane. Int J Cancer. 1995 Nov 27;63(5):716-9. doi: 10.1002/ijc.2910630518.
- Background: PubMed 3218971Kellen JA, Mirakian A, Kolin A. Antimetastatic effect of amiloride in an animal tumour model. Anticancer Res. 1988 Nov-Dec;8(6):1373-6.
- Background: PubMed 8127003Laurens WE, Vanrenterghem YF, Steels PS, Van Damme BJ. A new single nephron model of focal and segmental glomerulosclerosis in the Munich-Wistar rat. Kidney Int. 1994 Jan;45(1):143-9. doi: 10.1038/ki.1994.17.
- Background: PubMed 8413456Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993 Nov 11;329(20):1456-62. doi: 10.1056/NEJM199311113292004.
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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.
Wen Shen, MD, PhD principal investigator
Georgetown University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Amiloride and Triamterene in people with Proteinuria, run by Georgetown University 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 4 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 7 Feb 2020. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Margie Dimatulac (202-444-1210, mcd136@georgetown.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24 hr urine protein excretion (time frame: 20 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 NCT02522650, which also lists 31 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 7 Feb 2020.