Chronic Kidney DiseasePhase 1NCT00722215
Endothelin Receptor Antagonism in Proteinuric Nephropathy
A Phase 1 study testing BQ-123 (selective endothelin A receptor antagonist), 0.9 % saline and Nifedipine in people with Chronic Kidney Disease and Proteinuria, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
The number of people with kidney problems is increasing rapidly, related in part to the increasing prevalence of diabetes. Patients with kidney problems tend to have protein leaking into the urine (proteinuria). Both proteinuria and the kidney disease itself are associated with an increased risk of heart disease. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Kidney Disease, Proteinuria
- What is being tested?
- BQ-123 (selective endothelin A receptor antagonist), 0.9 % saline and Nifedipine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2006to Dec 2007
- Phase
- Phase 1
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female
- Age 18-70
- Body mass index <35
- Blood pressure <160/110 mmHg
- CKD stage 2-5 as per the K/DOQI classification
- Proteinuria in one of the following categories: 0.3-1.5, >1.5-3.0, and >3.0-6.0 g/24hrs
- Normal serum albumin
Who cannot join
- Subject is below the age of legal consent, or is mentally or legally incapacitated
- History of multiple and/or severe allergic reactions to drugs (including study drugs), or food
- The subject has donated blood (450 ml) within the last 4 weeks
- Past or present drug or alcohol abuse including intravenous drug abuse at any time
- Participation in another clinical trial within 1 month
- Considered to be at high risk of HIV or hepatitis B
- Pregnant
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Research Centre, Western General Hospital
Edinburgh, Scotland, EH4 2XU
About this study
Official title: The Systemic & Renal Effects of Endothelin Receptor Antagonism in Proteinuric Nephropathy
The number of people with kidney problems is increasing rapidly, related in part to the increasing prevalence of diabetes. Patients with kidney problems tend to have protein leaking into the urine (proteinuria). Both proteinuria and the kidney disease itself are associated with an increased risk of heart disease. Reducing proteinuria is an important treatment goal in people with kidney problems. Endothelin is a chemical produced both by blood vessels and the kidney. Higher than normal levels of endothelin are thought to contribute to progression of kidney disease and proteinuria. By using drugs that block the effects of endothelin ('endothelin receptor antagonists') we can hopefully reduce both of these. The purpose of the study is to ascertain whether endothelin receptor antagonists improve kidney function and reduce proteinuria more so than other commonly used drugs.
Read the detailed description
Response to ETA Receptor Antagonism/Nifedipine/Placebo Prior to the study visit subjects will be asked to refrain from alcohol for 24 hours. Tea and coffee will not be permitted for at least 12 hours before each visit. Studies will be conducted in a quiet, temperature-controlled room.
On arrival at the Clinical Research Centre on the study day, a brief medical enquiry and examination will confirm the ongoing suitability of the subject for the study. An intravenous cannula will be inserted into the antecubital fossa of each arm. We have developed a basic protocol described fully in our previous studies that allows us to measure systemic haemodynamics by the well validated technique of bioimpedance and renal function by standard para-aminohippurate (PAH; renal blood flow) and inulin (glomerular filtration rate) clearance studies.
Urinary protein excretion will be measured by collecting urine over 30 minute time periods. To ascertain the contribution of renal haemodynamics to any change in protein excretion renal blood flow and glomerular filtration rate will be measured. In addition, blood and urine will also be assayed for sodium, creatinine and osmolality to allow calculation of fractional excretion of sodium and free water clearance.
Systemic haemodynamic monitoring will be performed at 15 minute intervals during drug/placebo administration and at 30 minute intervals outwith these periods.
- Conditions
- Chronic Kidney Disease, Proteinuria
- Being tested
- BQ-123 (selective endothelin A receptor antagonist), 0.9 % saline, Nifedipine
- Keywords
- Endothelin antagonist, Chronic kidney disease, Proteinuria, Cardiovascular disease, Blood pressure, Arterial stiffness, Endothelial function
- Medical subject headings
- Renal Insufficiency, Chronic, Proteinuria, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BQ-123 (selective endothelin A receptor antagonist)Drug
Single dose of BQ-123 given at a dose of 1000 nmol/min for 15 min intravenously.
0.9 % salineDrug
Single 15ml 0.9% saline infused for 15 mins as placebo control
NifedipineDrug
Also called Adalat
Single dose of nifedipine 10 mg given orally as active control
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Placebo control arm of study Receives: Drug: 0.9 % saline |
| 2 | Experimental | BQ-123 arm of study Receives: Drug: BQ-123 (selective endothelin A receptor antagonist) |
| 3 | Active comparator | Nifedipine arm of study Receives: Drug: Nifedipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proteinuria
Measured: Acute change in proteinuria over 4 hour period following BQ-123 dosing
Blood pressure
Measured: Acute change in blood pressure over 4 hour period following BQ-123 dosing
Secondary outcomes (2)
Arterial stiffness (as measured by pulse wave velocity)
Measured: Acute change in arterial stiffness over 4 hour period following BQ-123 dosing
Endothelial function (as measured by flow-mediated dilatation)
Measured: Acute change in endothelial function over 4 hour period following BQ-123 dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2008 (estimated)
- Study startMay 2006
- Primary completionNov 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation
- Investigators
- Neeraj Dhaun, MBChB, Principal investigator, University of EdinburghDavid J Webb, MD, Study director, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00722215
- Sponsor's protocol ID
- 2006/WCRC/02
- Other IDs
- PG/05/91, 06/MRE00/12
- Status last verified
- Aug 2006
- First submitted
- 23 Jul 2008
- Last updated
- 25 Jul 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Systemic & Renal Effects of Endothelin Receptor Antagonism in Proteinuric Nephropathy
- ClinicalTrials.gov ID
- NCT00722215
- Acronym / sponsor ID
- 2006/WCRC/02
- Conditions
- Chronic Kidney Disease, Proteinuria
- Keywords
- Endothelin antagonist, Chronic kidney disease, Proteinuria, Cardiovascular disease, Blood pressure, Arterial stiffness, Endothelial function
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- British Heart Foundation
- Study start
- May 2006
- Primary completion
- Nov 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 25 Jul 2008 (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 number of people with kidney problems is increasing rapidly, related in part to the increasing prevalence of diabetes. Patients with kidney problems tend to have protein leaking into the urine (proteinuria). Both proteinuria and the kidney disease itself are associated with an increased risk of heart disease. Reducing proteinuria is an important treatment goal in people with kidney problems. Endothelin is a chemical produced both by blood vessels and the kidney. Higher than normal levels of endothelin are thought to contribute to progression of kidney disease and proteinuria. By using drugs that block the effects of endothelin ('endothelin receptor antagonists') we can hopefully reduce both of these. The purpose of the study is to ascertain whether endothelin receptor antagonists improve kidney function and reduce proteinuria more so than other commonly used drugs.
Detailed description
Response to ETA Receptor Antagonism/Nifedipine/Placebo Prior to the study visit subjects will be asked to refrain from alcohol for 24 hours. Tea and coffee will not be permitted for at least 12 hours before each visit. Studies will be conducted in a quiet, temperature-controlled room.
On arrival at the Clinical Research Centre on the study day, a brief medical enquiry and examination will confirm the ongoing suitability of the subject for the study. An intravenous cannula will be inserted into the antecubital fossa of each arm. We have developed a basic protocol described fully in our previous studies that allows us to measure systemic haemodynamics by the well validated technique of bioimpedance and renal function by standard para-aminohippurate (PAH; renal blood flow) and inulin (glomerular filtration rate) clearance studies.
Urinary protein excretion will be measured by collecting urine over 30 minute time periods. To ascertain the contribution of renal haemodynamics to any change in protein excretion renal blood flow and glomerular filtration rate will be measured. In addition, blood and urine will also be assayed for sodium, creatinine and osmolality to allow calculation of fractional excretion of sodium and free water clearance.
Systemic haemodynamic monitoring will be performed at 15 minute intervals during drug/placebo administration and at 30 minute intervals outwith these periods.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: 0.9 % salinePlacebo control arm of study |
| 2 | Experimental | Drug: BQ-123 (selective endothelin A receptor antagonist)BQ-123 arm of study |
| 3 | Active comparator | Drug: NifedipineNifedipine arm of study |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female
- Age 18-70
- Body mass index <35
- Blood pressure <160/110 mmHg
- CKD stage 2-5 as per the K/DOQI classification
Key exclusion criteria (7 listed)
- Subject is below the age of legal consent, or is mentally or legally incapacitated
- History of multiple and/or severe allergic reactions to drugs (including study drugs), or food
- The subject has donated blood (450 ml) within the last 4 weeks
- Past or present drug or alcohol abuse including intravenous drug abuse at any time
- Participation in another clinical trial within 1 month
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 |
|---|---|---|
| BQ-123 (selective endothelin A receptor antagonist)Single dose of BQ-123 given at a dose of 1000 nmol/min for 15 min intravenously. | Drug | 2 |
| 0.9 % salineSingle 15ml 0.9% saline infused for 15 mins as placebo control | Drug | 1 |
| NifedipineAlso: AdalatSingle dose of nifedipine 10 mg given orally as active control | Drug | 3 |
Primary outcome
Proteinuria
Time frame: Acute change in proteinuria over 4 hour period following BQ-123 dosing
Blood pressure
Time frame: Acute change in blood pressure over 4 hour period following BQ-123 dosing
2 secondary outcomes
Arterial stiffness (as measured by pulse wave velocity)
Time frame: Acute change in arterial stiffness over 4 hour period following BQ-123 dosing
Endothelial function (as measured by flow-mediated dilatation)
Time frame: Acute change in endothelial function over 4 hour period following BQ-123 dosing
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 25 Jul 2008.
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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.
Neeraj Dhaun, MBChB principal investigator
University of Edinburgh
David J Webb, MD study director
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BQ-123 (selective endothelin A receptor antagonist), 0.9 % saline and Nifedipine in people with Chronic Kidney Disease and Proteinuria, run by University of Edinburgh at 1 site in United Kingdom.
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 7 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 25 Jul 2008. 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 Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Proteinuria (time frame: Acute change in proteinuria over 4 hour period following BQ-123 dosing). The study lists 2 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 25 Jul 2008.