Renal TransplantPhase 2COSTANTNCT01224860
Telmisartan Versus Losartan in Kidney Transplantation
A Phase 2 study testing Telmisartan and Losartan in people with Renal Transplant, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
Trial summary
In renal transplant recipients, residual renal insufficiency combined to the effects of immunosuppressive therapy with steroids or calcineurin inhibitors may reduce insulin activity and may contribute to several of the abnormalities associated with the metabolic syndrome, such as hypertension, glucose intolerance and… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Renal Transplant
- What is being tested?
- Telmisartan and Losartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2009to Jan 2014
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent;
- Age > 18 years;
- Single renal transplant or dual marginal > 6 months duration;
- Blood pressure >130/85 mmHg or need for anti-hypertensive therapy;
- Stable renal function (changes in serum creatinine < 30%) and no acute rejection episodes in the last six months;
- Stable (for at least six months) dual or triple immunosuppressive therapy including corticosteroids or calcineurin inhibitors;
- Legal capacity.
Who cannot join
- Vascular disease of the kidney;
- Heart failure: NYHA classification class III-IV on ACE or AII inhibitor therapy;
- Cerebral haemorrhage, stroke or TIA within three months prior to study enrolment;
- Myocardial infarction within three months prior to study enrolment;
- Unstable angina pectoris;
- Severe hepatic disease;
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- Pregnancy or women of child-bearing potential without following a scientifically accepted form of contraception;
- Overt diabetes or concomitant treatment with oral antidiabetic agents and/or insulin;
- Specific clinical indication (other than arterial hypertension) to be treated with ACE inhibitors or AII receptor antagonists;
- Specific contraindications or history of hypersensitivity to the study drugs, glitazones, ACE inhibitors or AII receptor antagonists;
- Participation to other clinical trials over the last three months;
- Legal incapacity;
- Previous diagnosis of: intellectual disability/mental retardation, dementia, schizophrenia.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Mario negri Institute - Clinical Research Center for Rare Diseases
Ranica, Bergamo, 24020
About this study
Official title: A Prospective, Randomized, Open Label Blinded End Point (Probe), Crossover Study to Compare the Effects of Telmisartan and Losartan on Metabolic Profile of Renal Transplant Patients
In renal transplant recipients, residual renal insufficiency combined to the effects of immunosuppressive therapy with steroids or calcineurin inhibitors may reduce insulin activity and may contribute to several of the abnormalities associated with the metabolic syndrome, such as hypertension, glucose intolerance and hyperlipidemia. In turn, insulin resistance, hypertension, hyperglycemia and dyslipidemia may importantly contribute to the excess cardiovascular risk of renal transplant patients (an excess comparable to that of diabetes subjects with over diabetic nephropathy)and may also accelerate progressive renal function deterioration and promote graft loss. Thus, amelioration of the insulin activity and of the related metabolic syndrome is a key component of treatments aimed to improve patient and graft survival in renal transplant recipients. Recently, drugs such as peroxisome proliferators-activated receptor-gamma activators, that ameliorate insulin sensitivity and metabolic syndrome, have become available.These agents, however, can provoke fluid retention, weight gain, edema and, in some cases, heart failure.
Recent studies showed that telmisartan, an angiotensin II type 1 receptor antagonist, in addition to block the angiotensin II type 1 - a key surface receptor involved in the regulation of blood pressure - may also activate peroxisome proliferators-activated receptor-gamma activators, thus improving some of the features of the metabolic syndrome. Thus telmisartan may substantially reduce the overall cardiovascular and renal risk of renal transplant recipients by ameliorating some of the modifiable components of the metabolic syndrome. On the other hand, telmisartan is devoid of the adverse effects of peroxisome proliferators-activated receptor-gamma activators such as fluid retention, and has therefore a remarkably better risk/benefit profile. Thus, whether telmisartan in addition to the beneficial effects of a reference angiotensin II type 1 receptor antagonist (such as losartan) may offer adjunctive advantages related to improved insulin sensitivity in renal transplant patients on chronic therapy with steroids and/or calcineurin inhibitors, is worth investigating.
Read the detailed description
BACKGROUND In renal transplant recipients, residual renal insufficiency combined to the effects of immunosuppressive therapy with steroids or calcineurin inhibitors may reduce insulin activity and may contribute to several of the abnormalities associated with the metabolic syndrome, such as hypertension, glucose intolerance and hyperlipidemia. In turn, insulin resistance, hypertension, hyperglycemia and dyslipidemia may importantly contribute to the excess cardiovascular risk of renal transplant patients (an excess comparable to that of diabetes subjects with over diabetic nephropathy)and may also accelerate progressive renal function deterioration and promote graft loss. Thus, amelioration of the insulin activity and of the related metabolic syndrome is a key component of treatments aimed to improve patient and graft survival in renal transplant recipients. Recently, drugs such as peroxisome proliferators-activated receptor-gamma activators, that ameliorate insulin sensitivity and metabolic syndrome, have become available. These agents, however, can provoke fluid retention, weight gain, edema and, in some cases, heart failure. Thus, the risk/benefit profile of peroxisome proliferators-activated receptor-gamma activators is still uncertain, in particular in renal transplant patients where the risks of therapy may overwhelm the potential benefits.
Recent studies showed that telmisartan, an angiotensin II type 1 receptor antagonist, in addition to block the angiotensin II type 1 - a key surface receptor involved in the regulation of blood pressure - may also activate PPAR-gamma, thus improving some of the features of the metabolic syndrome, such as hyperglycemia and dyslipidemia in people with hypertension and/or diabetes. Thus, in addition to control high blood pressure and to limit some of the adverse effects of angiotensin II, including target organ damage, graft fibrosis and cyclosporine (CsA) nephrotoxicity, telmisartan may also substantially reduce the overall cardiovascular and renal risk of renal transplant recipients by ameliorating some of the modifiable components of the metabolic syndrome, such as hypertension, glucose intolerance and hyperlipidemia. On the other hand, telmisartan is devoid of the adverse effects of peroxisome proliferators-activated receptor-gamma activators such as fluid retention, and has therefore a remarkably better risk/benefit profile. Thus, whether telmisartan in addition to the beneficial effects of a reference AII receptor antagonist (such as losartan) may offer adjunctive advantages related to improved insulin sensitivity in renal transplant patients on chronic therapy with steroids and/or calcineurin inhibitors, is worth investigating.
AIMS The primary aim is to compare the short-term effects of telmisartan and losartan on insulin sensitivity in kidney transplant recipients with stable renal function and concomitant treatment with steroids and/or calcineurin inhibitors.
DESIGN This will be a pilot, explorative study. On the basis of previous experimental evidence, a crossover study on 20 patients should have the power to detect a statistically significant difference in the effect on insulin activity between each treatment period as compared to baseline.
Patients will be randomised on a 1:1 basis to the sequence Telmisartan-Losartan or to sequence losartan-telmisartan.
- Conditions
- Renal Transplant
- Being tested
- Telmisartan, Losartan
- Keywords
- Telmisartan, Losartan, Renal transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TelmisartanDrug
One week 40 mg daily, followed by fifteen weeks treatment period with 80 mg daily.
LosartanDrug
One week 50 mg daily, followed by fifteen weeks treatment period with 100 mg daily.
| Study group | Role | What they receive |
|---|---|---|
| Telmisartan | Experimental | Not described Receives: Drug: Telmisartan |
| Losartan | Experimental | Not described Receives: Drug: Losartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity.
Glucose disposal rate as assessed by an euglycemic hyperinsulinemic clamp.
Measured: At baseline and then every four months.
Insulin sensitivity.
Glucose disposal rate as assessed by an euglycemic hyperinsulinemic clamp.
Measured: At 9 month.
Secondary outcomes (6)
Systemic variables.
Sitting systolic/diastolic blood pressure, 24-h blood pressure profile.
Measured: At baseline and then every four months.
Systemic variables.
Sitting systolic/diastolic blood pressure, 24-h blood pressure profile.
Measured: At 9 month.
Metabolic variables.
Morning fasting blood glucose, Glucose tolerance test, Glicated hemoglobin, Morning fasting insulin, HOMA index, Lipid profile (total cholesterol, triglycerides, HDL, LDL, apolipoprotein A, B.
Measured: At baseline and then every four months.
Metabolic variables.
Morning fasting blood glucose, Glucose tolerance test, Glicated hemoglobin, Morning fasting insulin, HOMA index, Lipid profile (total cholesterol, triglycerides, HDL, LDL, apolipoprotein A, B.
Measured: At 9 month.
Renal variables.
UAE (as assessed by nephelometry in three consecutive overnight urine collections), GFR/RPF (as assessed by Iohexol and PAH plasma clearance, respectively), Albumin fractional clearance.
Measured: At baseline and then every four months.
Renal variables.
UAE (as assessed by nephelometry in three consecutive overnight urine collections), GFR/RPF (as assessed by Iohexol and PAH plasma clearance, respectively), Albumin fractional clearance.
Measured: At 9 month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2010 (estimated)
- Study startJan 2009
- Primary completionJun 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal TransplantStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01224860
- Sponsor's protocol ID
- COSTANT
- Other IDs
- 2008-000822-38, 2008
- Acronym
- COSTANT
- Status last verified
- Feb 2014
- First submitted
- 19 Oct 2010
- Last updated
- 25 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.
PubMed 39082471
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Open Label Blinded End Point (Probe), Crossover Study to Compare the Effects of Telmisartan and Losartan on Metabolic Profile of Renal Transplant Patients
- ClinicalTrials.gov ID
- NCT01224860
- Acronym / sponsor ID
- COSTANT / COSTANT
- Conditions
- Renal Transplant
- Keywords
- Telmisartan, Losartan, Renal transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 20 Oct 2010 (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.
In renal transplant recipients, residual renal insufficiency combined to the effects of immunosuppressive therapy with steroids or calcineurin inhibitors may reduce insulin activity and may contribute to several of the abnormalities associated with the metabolic syndrome, such as hypertension, glucose intolerance and hyperlipidemia. In turn, insulin resistance, hypertension, hyperglycemia and dyslipidemia may importantly contribute to the excess cardiovascular risk of renal transplant patients (an excess comparable to that of diabetes subjects with over diabetic nephropathy)and may also accelerate progressive renal function deterioration and promote graft loss. Thus, amelioration of the insulin activity and of the related metabolic syndrome is a key component of treatments aimed to improve patient and graft survival in renal transplant recipients. Recently, drugs such as peroxisome proliferators-activated receptor-gamma activators, that ameliorate insulin sensitivity and metabolic syndrome, have become available.These agents, however, can provoke fluid retention, weight gain, edema and, in some cases, heart failure.
Recent studies showed that telmisartan, an angiotensin II type 1 receptor antagonist, in addition to block the angiotensin II type 1 - a key surface receptor involved in the regulation of blood pressure - may also activate peroxisome proliferators-activated receptor-gamma activators, thus improving some of the features of the metabolic syndrome. Thus telmisartan may substantially reduce the overall cardiovascular and renal risk of renal transplant recipients by ameliorating some of the modifiable components of the metabolic syndrome. On the other hand, telmisartan is devoid of the adverse effects of peroxisome proliferators-activated receptor-gamma activators such as fluid retention, and has therefore a remarkably better risk/benefit profile. Thus, whether telmisartan in addition to the beneficial effects of a reference angiotensin II type 1 receptor antagonist (such as losartan) may offer adjunctive advantages related to improved insulin sensitivity in renal transplant patients on chronic therapy with steroids and/or calcineurin inhibitors, is worth investigating.
Detailed description
BACKGROUND In renal transplant recipients, residual renal insufficiency combined to the effects of immunosuppressive therapy with steroids or calcineurin inhibitors may reduce insulin activity and may contribute to several of the abnormalities associated with the metabolic syndrome, such as hypertension, glucose intolerance and hyperlipidemia. In turn, insulin resistance, hypertension, hyperglycemia and dyslipidemia may importantly contribute to the excess cardiovascular risk of renal transplant patients (an excess comparable to that of diabetes subjects with over diabetic nephropathy)and may also accelerate progressive renal function deterioration and promote graft loss. Thus, amelioration of the insulin activity and of the related metabolic syndrome is a key component of treatments aimed to improve patient and graft survival in renal transplant recipients. Recently, drugs such as peroxisome proliferators-activated receptor-gamma activators, that ameliorate insulin sensitivity and metabolic syndrome, have become available. These agents, however, can provoke fluid retention, weight gain, edema and, in some cases, heart failure. Thus, the risk/benefit profile of peroxisome proliferators-activated receptor-gamma activators is still uncertain, in particular in renal transplant patients where the risks of therapy may overwhelm the potential benefits.
Recent studies showed that telmisartan, an angiotensin II type 1 receptor antagonist, in addition to block the angiotensin II type 1 - a key surface receptor involved in the regulation of blood pressure - may also activate PPAR-gamma, thus improving some of the features of the metabolic syndrome, such as hyperglycemia and dyslipidemia in people with hypertension and/or diabetes. Thus, in addition to control high blood pressure and to limit some of the adverse effects of angiotensin II, including target organ damage, graft fibrosis and cyclosporine (CsA) nephrotoxicity, telmisartan may also substantially reduce the overall cardiovascular and renal risk of renal transplant recipients by ameliorating some of the modifiable components of the metabolic syndrome, such as hypertension, glucose intolerance and hyperlipidemia. On the other hand, telmisartan is devoid of the adverse effects of peroxisome proliferators-activated receptor-gamma activators such as fluid retention, and has therefore a remarkably better risk/benefit profile. Thus, whether telmisartan in addition to the beneficial effects of a reference AII receptor antagonist (such as losartan) may offer adjunctive advantages related to improved insulin sensitivity in renal transplant patients on chronic therapy with steroids and/or calcineurin inhibitors, is worth investigating.
AIMS The primary aim is to compare the short-term effects of telmisartan and losartan on insulin sensitivity in kidney transplant recipients with stable renal function and concomitant treatment with steroids and/or calcineurin inhibitors.
DESIGN This will be a pilot, explorative study. On the basis of previous experimental evidence, a crossover study on 20 patients should have the power to detect a statistically significant difference in the effect on insulin activity between each treatment period as compared to baseline.
Patients will be randomised on a 1:1 basis to the sequence Telmisartan-Losartan or to sequence losartan-telmisartan.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Telmisartan | Experimental | Drug: Telmisartan |
| Losartan | Experimental | Drug: Losartan |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Informed consent;
- Age > 18 years;
- Single renal transplant or dual marginal > 6 months duration;
- Blood pressure >130/85 mmHg or need for anti-hypertensive therapy;
- Stable renal function (changes in serum creatinine < 30%) and no acute rejection episodes in the last six months;
Key exclusion criteria (13 listed)
- Vascular disease of the kidney;
- Heart failure: NYHA classification class III-IV on ACE or AII inhibitor therapy;
- Cerebral haemorrhage, stroke or TIA within three months prior to study enrolment;
- Myocardial infarction within three months prior to study enrolment;
- Unstable angina pectoris;
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 |
|---|---|---|
| TelmisartanOne week 40 mg daily, followed by fifteen weeks treatment period with 80 mg daily. | Drug | Telmisartan |
| LosartanOne week 50 mg daily, followed by fifteen weeks treatment period with 100 mg daily. | Drug | Losartan |
Primary outcome
Insulin sensitivity.
Time frame: At baseline and then every four months.
Glucose disposal rate as assessed by an euglycemic hyperinsulinemic clamp.
Insulin sensitivity.
Time frame: At 9 month.
Glucose disposal rate as assessed by an euglycemic hyperinsulinemic clamp.
6 secondary outcomes
Systemic variables.
Time frame: At baseline and then every four months.
Systemic variables.
Time frame: At 9 month.
Metabolic variables.
Time frame: At baseline and then every four months.
Metabolic variables.
Time frame: At 9 month.
Renal variables.
Time frame: At baseline and then every four months.
Renal variables.
Time frame: At 9 month.
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 Feb 2014.
- Derived from this study: PubMed 39082471Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Telmisartan and Losartan in people with Renal Transplant, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
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 13 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 Feb 2014. 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 Italy. 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?
Insulin sensitivity. (time frame: At baseline and then every four months.). 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?
On the ClinicalTrials.gov record for NCT01224860, which also lists 1 linked publication.
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 Feb 2014.