DiabetesPhase 4NCT00921570
The Effects of Renin Angiotensin System Blockage (RAS), Calcium Channel Blocker and Combined Drugs on TWEAK, PTX3 and FMD Levels in Diabetic Proteinuric Patients With Hypertension
A Phase 4 study testing Amlodipine and Valsartan in people with Diabetes and Hypertension, run by Gulhane School of Medicine at 1 site in Turkey (Türkiye).
Trial summary
Diabetic nephropathy (DN) is the most important complication of diabetes mellitus (DM) and the most common cause of end-stage renal disease (ESRD). Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (> 300 mg/d or > 200 mcg/min) that is confirmed on at least 2 occasions 3 to 6 months… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diabetes, Hypertension, Proteinuria
- What is being tested?
- Amlodipine and Valsartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- Feb 2008to May 2009
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- CKD stage 1 patients
- Older than 18 years of age
- Type 2 Diabetic patients
- Proteinuria
- Hypertension
Who cannot join
- History of coronary artery disease
- Smokers
- Taking statins or renin-angiotensin blockers
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of Renin Angiotensin System Blockage (RAS), Calcium Channel Blocker and Combine Drugs on TWEAK, PTX3 and FMD Levels in Diabetic Proteinuric Patients With Hypertension
Diabetic nephropathy (DN) is the most important complication of diabetes mellitus (DM) and the most common cause of end-stage renal disease (ESRD). Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (> 300 mg/d or > 200 mcg/min) that is confirmed on at least 2 occasions 3 to 6 months apart, a relentless decline in the glomerular filtration rate (GFR), and elevated arterial blood pressure. In addition to the renal hemodynamic alterations, patients with overt diabetic nephropathy (dipstick-positive proteinuria and decreasing GFR) generally develop systemic hypertension. Hypertension is an adverse factor in all progressive renal diseases and seems especially so in diabetic nephropathy. The deleterious effects of hypertension are likely directed at the vasculature and microvasculature. Use of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs), strict glycemic control and use of antilipidemic drugs may improve progression of DN.
TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) is a member of the TNF superfamily of structurally related cytokines. The human TWEAK gene encodes a 249-amino acid type II transmembrane glycoprotein (30 kD). TWEAK may be expressed as a full-length, membrane-bound protein and as a 156-amino acid, 18-kD soluble protein, (sTWEAK) that results from proteolysis of TWEAK. TWEAK gene is expressed in many tissues, including brain, kidney, heart, arterial wall, monocytes and macrophages. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and chronic kidney disease (CKD).
Read more
Long pentraxin 3 (PTX3) is a multimeric inflammatory mediator. Increased serum PTX3 levels have been reported among end-stage renal disease patients. Moreover, PTX3 has been suggested to represent a novel mortality risk factor, and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease (CKD).
There is no data about the effects of Renin angiotensin system blockage (RAS), calcium channel blocker and combined drugs on TWEAK and PTX3 levels in diabetic proteinuric patients with hypertension. The aim of this study was to find out whether the beneficial effects of RAS blockage, calcium channel blocker and combined drugs in diabetic hypertensive proteinuric patients has any relation with the alteration of TWEAK and PTX3 levels. The investigators searched for the effects of angiotensin II (AII) receptor blocker (Valsartan 160 mg), calcium channel blocker (Amlodipine 10 mg) and AII receptor blocker plus calcium channel blocker (Valsartan 160 mg + Amlodipine 10 mg) on the clinical and laboratory parameters of diabetic hypertensive proteinuric patients.
Read the detailed description
The patients who were non-obese (BMI<30kg/m2), non dyslipidemic (total cholesterol <200mg/dl, Triglyceride<150mg/dl), and free of cardiovascular events (negative medical history, negative ECG findings) were investigated for enrollment. CKD stage 1 patients older than 18 years of age and willing to participate to the study were screened. From the 375 patients with established type 2 diabetes mellitus+hypertension, 174 had proteinuria and/or hypertension (24 h protein excretion 1-2 g/day, systolic blood pressures ≥140mmHg and/or diastolic blood pressures ≥ 90 mmHg, respectively). All cases were first referrals and at the time of the study all were off treatment. Patients with history of coronary artery disease, smokers and those taking statins or renin-angiotensin blockers were excluded because of the effect of these factors on endothelial dysfunction. Of 174 screened patients 107 met the study criteria and were included in this study. The duration of proteinuria and diabetic nephropathy after initial diagnosis was not known.
The exclusion criteria were as follows: A)Nephrotic syndrome, B)coronary heart disease (patients with ischemic ST-T alterations and voltage criteria for LVH on electrocardiogram, and with history of revascularization or myocardial infarction), C) elevated liver enzymes (AST or ALT levels ≥ 40U/L) and D) renal failure (serum creatinine levels > 1.3 mg/dl). In order to evaluate the effect of RAS blockade on plasma TWEAK and PTX3 concentrations, patients with proteinuria were given an AII receptor blocker (Valsartan 160 mg), calcium channel blocker (Amlodipine 10 mg) and combine drug (Valsartan 160 mg + Amlodipine 10 mg) for 12 weeks. The effect of RAS blockade on insulin sensitivity and proteinuria was also investigated.
After the intervention period, blood samples were obtained for assay of plasma TWEAK and PTX3 concentrations, HbA1c , and insulin resistance scores (HOMA-IR).
Urine samples were also collected over a 24-hour period to determine the degree of proteinuria.
- Conditions
- Diabetes, Hypertension, Proteinuria
- Being tested
- Amlodipine, Valsartan
- Keywords
- TWEAK, FMD, PTX3, Valsartan, Amlodipine, Renin Angiotensin System
- Medical subject headings
- Diabetes Mellitus, Hypertension, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmlodipineDrug
calcium channel blocker (Amlodipine 10 mg) during 12 weeks
ValsartanDrug
AII receptor blocker inhibitor (Valsartan 160 mg) during 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Amlodipine | Experimental | Not described Receives: Drug: Amlodipine |
| Valsartan | Experimental | Not described Receives: Drug: Valsartan |
| Valsartan+Amlodipine | Experimental | Not described Receives: Drug: Amlodipine; Drug: Valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flow mediated dilatation
Measured: 12 weeks after
Secondary outcomes (1)
TWEAK, PTX-3, Systolic Blood Pressure and Diastolic Blood Pressure
Measured: 12 weeks after
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2009 (estimated)
- Study startFeb 2008
- Primary completionMay 2009
- Study completionMay 2009
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 DiabetesStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gulhane School of Medicine
- Sponsor type
- University, hospital or other
- Investigators
- Mahmut Ilker Yilmaz, MD, Principal investigator, GATA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00921570
- Sponsor's protocol ID
- GATA VALAMEX study
- Status last verified
- Jun 2009
- First submitted
- 15 Jun 2009
- Last updated
- 17 Jun 2009
- Results posted
- No
Publications
Yilmaz MI, Carrero JJ, Martin-Ventura JL, Sonmez A, Saglam M, Celik T, Yaman H, Yenicesu M, Eyileten T, Moreno JA, Egido J, Blanco-Colio LM. Combined therapy with renin-angiotensin system and calcium channel blockers in type 2 diabetic hypertensive patients with proteinuria: effects on soluble TWEAK, PTX3, and flow-mediated dilation. Clin J Am Soc Nephrol. 2010 Jul;5(7):1174-81. doi: 10.2215/CJN.01110210. Epub 2010 Apr 29.
PubMed 20430947
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Renin Angiotensin System Blockage (RAS), Calcium Channel Blocker and Combine Drugs on TWEAK, PTX3 and FMD Levels in Diabetic Proteinuric Patients With Hypertension
- ClinicalTrials.gov ID
- NCT00921570
- Acronym / sponsor ID
- GATA VALAMEX study
- Conditions
- Diabetes, Hypertension, Proteinuria
- Keywords
- TWEAK, FMD, PTX3, Valsartan, Amlodipine, Renin Angiotensin System
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Gulhane School of MedicineUniversity, hospital or other
- Study start
- Feb 2008
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 16 Jun 2009 (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.
Diabetic nephropathy (DN) is the most important complication of diabetes mellitus (DM) and the most common cause of end-stage renal disease (ESRD). Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (> 300 mg/d or > 200 mcg/min) that is confirmed on at least 2 occasions 3 to 6 months apart, a relentless decline in the glomerular filtration rate (GFR), and elevated arterial blood pressure. In addition to the renal hemodynamic alterations, patients with overt diabetic nephropathy (dipstick-positive proteinuria and decreasing GFR) generally develop systemic hypertension. Hypertension is an adverse factor in all progressive renal diseases and seems especially so in diabetic nephropathy. The deleterious effects of hypertension are likely directed at the vasculature and microvasculature. Use of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs), strict glycemic control and use of antilipidemic drugs may improve progression of DN.
TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) is a member of the TNF superfamily of structurally related cytokines. The human TWEAK gene encodes a 249-amino acid type II transmembrane glycoprotein (30 kD). TWEAK may be expressed as a full-length, membrane-bound protein and as a 156-amino acid, 18-kD soluble protein, (sTWEAK) that results from proteolysis of TWEAK. TWEAK gene is expressed in many tissues, including brain, kidney, heart, arterial wall, monocytes and macrophages. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and chronic kidney disease (CKD).
Long pentraxin 3 (PTX3) is a multimeric inflammatory mediator. Increased serum PTX3 levels have been reported among end-stage renal disease patients. Moreover, PTX3 has been suggested to represent a novel mortality risk factor, and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease (CKD).
There is no data about the effects of Renin angiotensin system blockage (RAS), calcium channel blocker and combined drugs on TWEAK and PTX3 levels in diabetic proteinuric patients with hypertension. The aim of this study was to find out whether the beneficial effects of RAS blockage, calcium channel blocker and combined drugs in diabetic hypertensive proteinuric patients has any relation with the alteration of TWEAK and PTX3 levels. The investigators searched for the effects of angiotensin II (AII) receptor blocker (Valsartan 160 mg), calcium channel blocker (Amlodipine 10 mg) and AII receptor blocker plus calcium channel blocker (Valsartan 160 mg + Amlodipine 10 mg) on the clinical and laboratory parameters of diabetic hypertensive proteinuric patients.
Detailed description
The patients who were non-obese (BMI<30kg/m2), non dyslipidemic (total cholesterol <200mg/dl, Triglyceride<150mg/dl), and free of cardiovascular events (negative medical history, negative ECG findings) were investigated for enrollment. CKD stage 1 patients older than 18 years of age and willing to participate to the study were screened. From the 375 patients with established type 2 diabetes mellitus+hypertension, 174 had proteinuria and/or hypertension (24 h protein excretion 1-2 g/day, systolic blood pressures ≥140mmHg and/or diastolic blood pressures ≥ 90 mmHg, respectively). All cases were first referrals and at the time of the study all were off treatment. Patients with history of coronary artery disease, smokers and those taking statins or renin-angiotensin blockers were excluded because of the effect of these factors on endothelial dysfunction. Of 174 screened patients 107 met the study criteria and were included in this study. The duration of proteinuria and diabetic nephropathy after initial diagnosis was not known.
The exclusion criteria were as follows: A)Nephrotic syndrome, B)coronary heart disease (patients with ischemic ST-T alterations and voltage criteria for LVH on electrocardiogram, and with history of revascularization or myocardial infarction), C) elevated liver enzymes (AST or ALT levels ≥ 40U/L) and D) renal failure (serum creatinine levels > 1.3 mg/dl). In order to evaluate the effect of RAS blockade on plasma TWEAK and PTX3 concentrations, patients with proteinuria were given an AII receptor blocker (Valsartan 160 mg), calcium channel blocker (Amlodipine 10 mg) and combine drug (Valsartan 160 mg + Amlodipine 10 mg) for 12 weeks. The effect of RAS blockade on insulin sensitivity and proteinuria was also investigated.
After the intervention period, blood samples were obtained for assay of plasma TWEAK and PTX3 concentrations, HbA1c , and insulin resistance scores (HOMA-IR).
Urine samples were also collected over a 24-hour period to determine the degree of proteinuria.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Amlodipine | Experimental | Drug: Amlodipine |
| Valsartan | Experimental | Drug: Valsartan |
| Valsartan+Amlodipine | Experimental | Drug: Amlodipine, Drug: Valsartan |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- CKD stage 1 patients
- Older than 18 years of age
- Type 2 Diabetic patients
- Proteinuria
- Hypertension
Key exclusion criteria (3 listed)
- History of coronary artery disease
- Smokers
- Taking statins or renin-angiotensin blockers
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 |
|---|---|---|
| Amlodipinecalcium channel blocker (Amlodipine 10 mg) during 12 weeks | Drug | Amlodipine, Valsartan+Amlodipine |
| ValsartanAII receptor blocker inhibitor (Valsartan 160 mg) during 12 weeks | Drug | Valsartan, Valsartan+Amlodipine |
Primary outcome
Flow mediated dilatation
Time frame: 12 weeks after
1 secondary outcome
TWEAK, PTX-3, Systolic Blood Pressure and Diastolic Blood Pressure
Time frame: 12 weeks after
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 17 Jun 2009.
- Derived from this study: PubMed 20430947Yilmaz MI, Carrero JJ, Martin-Ventura JL, Sonmez A, Saglam M, Celik T, Yaman H, Yenicesu M, Eyileten T, Moreno JA, Egido J, Blanco-Colio LM. Combined therapy with renin-angiotensin system and calcium channel blockers in type 2 diabetic hypertensive patients with proteinuria: effects on soluble TWEAK, PTX3, and flow-mediated dilation. Clin J Am Soc Nephrol. 2010 Jul;5(7):1174-81. doi: 10.2215/CJN.01110210. Epub 2010 Apr 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.
Mahmut Ilker Yilmaz, MD principal investigator
GATA
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 Amlodipine and Valsartan in people with Diabetes and Hypertension, run by Gulhane School of Medicine at 1 site in Turkey (Türkiye).
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 5 inclusion and 3 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 17 Jun 2009. 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 Turkey (Türkiye). 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?
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?
Flow mediated dilatation (time frame: 12 weeks after). 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 NCT00921570, 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 17 Jun 2009.