Type 2 DiabetesPhase 3NCT00157586
Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND)
A Phase 3 study testing Delapril, Delapril-Manidipine Fixed combination in people with Type 2 Diabetes, run by Mario Negri Institute for Pharmacological Research at 8 sites in 2 countries.
Trial summary
Diabetes mellitus is one of the most common diseases globally, and is considered epidemic in many developed and newly industrialized nations. Diabetes mellitus represents the single largest cause of end-stage renal disease in the U.S. and Europe. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Delapril, Delapril-Manidipine Fixed combination
- How many people
- 342 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Feb 2002to Jun 2008
- Phase
- Phase 3
- 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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 40 years
- History of diabetes mellitus type 2 for at least three months with stable antidiabetic treatment
- Systolic and/or diastolic blood pressure ≥ 135 or 85 mmHg, respectively. In alternative, antihypertensive therapy regardless of blood pressure values
- Serum creatinine ≤ 1.5 mg/dL
- Urinary albumin excretion rate < 200 µg/min
- Written informed consent for the trial participation.
Who cannot join
- Clinical or histological evidence of non-diabetic renal disease, including vascular disease of the kidney, obstructive uropathy, prostatic hypertrophy or incomplete bladder emptying
- Transplanted kidney
- Moderate to severe chronic heart failure (III-IV stage according to the NYHA classification).
- Cerebral hemorrhage, stroke or transient ischemic attack within three months prior to the trial enrolment
- Myocardial infarction within three months prior to the trial enrolment
- Unstable angina pectoris
Show all 25Show fewer
- Mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
- Secondary (e.g., Cushing disease, phaeochromocytoma, etc.) or severe refractory hypertension
- Poor glycemic control (HbA1c>11%)
- Connective tissue or autoimmune disease
- Hereditary angioneurotic edema
- Clinically relevant electrolyte imbalance (e.g., serum potassium > 5.5 mmol/L)
- Clinically relevant hematological disorders
- Anemia with hemoglobin concentrations < 10 g/dL
- Serious hepatic disease
- Pregnancy or lactating or planning a pregnancy
- Women of childbearing potential without following a scientifically accepted form of contraception
- Any other serious or terminal concomitant disease
- Any condition which may interfere with the absorption of the study treatments
- Any concomitant treatment with ACE inhibitors, angiotensin II blockers, calcium channel blockers, potassium sparing diuretics
- Chronic treatment with nonsteroidal antiinflammatory drugs, antidepressants and neuroleptics, lithium, cimetidine, immunosuppressive and/or antineoplastic drugs, chronic systemic glucocorticoid therapy more than 7 consecutive days in one month, antiarrhythmic drugs (e.g., chinidin, procainamide), anesthetics/narcotics
- History of hypersensitivity to delapril or other ACE inhibitors, manidipine or other dihydropyridine CCBs
- Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the trial
- Evidence of an uncooperative attitude
- Any evidence that allows predicting that the patient will not be able to complete the trial follow-up.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Italy7 sites
Hospital "Ospedali Riuniti di Bergamo" - Diabetologic Unit
Bergamo, Bergamo, 24128
ASL of Ponte San Pietro - Diabetologic Unit
Ponte San Pietro, Bergamo, 24036
Clinical Research Center for Rare Diseases
Ranica, Bergamo, 24020
Hospital of Romano di Lombardia - Diabetologic Unit
Romano di Lombardia, Bergamo, 24058
Humanitas Institute - Endocrinology and Diabetologic Unit
Rozzano, Milano, 20089
Hospital " Bolognini " - Medicine Unit
Seriate, Bergamo, 24068
Hospital " Treviglio Caravaggio" - Diabetologic Unit
Treviglio, Bergamo, 24128
Slovenia1 site
Department of Endocrinolgy, Diabetes and Metabolic Disease - University Medical Center
Ljubljana, Ljubljana
About this study
Official title: A Multicenter, Randomized, Prospective, Double-blind Study to Evaluate the Nephroprotective Effect of Delapril Alone or Combined With Manidipine in Patients With Type 2 Diabetes
Diabetes mellitus is one of the most common diseases globally, and is considered epidemic in many developed and newly industrialized nations. Diabetes mellitus represents the single largest cause of end-stage renal disease in the U.S. and Europe. At the same time, the primary cause of early death in diabetic patients are cardiovascular complications. Experimental and clinical studies found that angiotensin converting enzyme inhibitors (ACEi) and calcium channel blockers (CCBs) have a specific renoprotective effect and that this effect can be magnified when the two drugs are used in combination. To formally test this hypothesis we designed the Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND) study, a prospective, randomized, double blind trial aimed to compare the effect of 3 years treatment with the ACEi Delapril (30 mg/day), alone or combined to the CCB Manidipine (10 mg/day), versus conventional (non ACEi, non CCB) therapy on the rate of renal function loss and on the incidence of major cardiovascular events in 342 normo- and micro-albuminuric hypertensive type 2 diabetic patients.
Read the detailed description
INTRODUCTION Optimal blood pressure, glycemic and lipid control are of utmost importance to minimize the incidence and the progression of chronic renal and cardiovascular complications in patients with diabetes mellitus type 2. Whether angiotensin converting enzyme (ACE) inhibitors alone or combined to calcium channel blockers (CCB) may further reduce the incidence and progression of chronic complications is worth investigating.
AIMS The primary aim of this study is to assess whether at comparable levels of optimal blood pressure and metabolic control, the ACE inhibitor delapril alone or in combination with the dihydropyridine CCB manidipine slow the rate of glomerular filtration rate (GFR) decline as compared with placebo plus conventional antihypertensive therapy in patients with diabetes mellitus type 2 and hypertension. The secondary aim of this study is to assess the effects of delapril and manidipine on the incidence of major cardiovascular events (acute myocardial infarction, ictus or stroke, heart failure requiring hospitalization, revascularization, amputation and cardiovascular mortality).
STUDY POPULATION 342 hypertensive type 2 diabetes patients with normo- or micro-albuminuria. STUDY DESIGN This is a multicenter, prospective, randomized, double-blind, placebo-controlled study. After a 12-week baseline period in which prohibited antihypertensive treatments (ACE inhibitors, angiotensin II receptor antagonists or dihydropyridine calcium channel blockers) will be discontinued, patients will be stratified according to their urinary albumin excretion rate in normo- and micro-albuminuric and then randomized to delapril alone (30 mg/day), delapril (30 mg/day) combined with manidipine (10 mg/day) or placebo given once daily in the morning for at least three years. During the study, systolic and diastolic blood pressure in all treatments groups will be maintained ≤ 120 and 80 mmHg respectively, with fixed doses of study treatments and flexible doses of permitted antihypertensive therapy (diuretics, beta blockers, alfa blockers, centrally acting adrenergic blockers. Blood pressure, blood glucose concentrations and urinary albumin excretion rate will be monitored every three months. Serum lipid concentrations and GFR (estimated with the iohexol plasma clearance) will be measured every six months.
Primary and Secondary Variables. The primary efficacy variable of this study is the rate of GFR decline. The secondary efficacy variable will be the incidence of major cardiovascular events (acute myocardial infarction, ictus or stroke, heart failure requiring hospitalization, revascularization, amputation and cardiovascular mortality).
- Conditions
- Type 2 Diabetes
- Being tested
- Delapril, Delapril-Manidipine Fixed combination
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Delapril, Delapril-Manidipine Fixed combinationDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of decline of glomerular filtration rate (GFR).GFR is measured at baseline,and at 6,12,18,24,30 and 36 months after randomization
Secondary outcomes (1)
Major cardiovascular events
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startFeb 2002
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies 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 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 342 participants
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Investigators
- Piero Ruggenenti, MD, Principal investigator, Mario Negri Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00157586
- Sponsor's protocol ID
- DM/PR/7401/005/00
- Status last verified
- Mar 2006
- First submitted
- 8 Sep 2005
- Last updated
- 9 Apr 2015
- Results posted
- No
Publications
Carrara F, Ruggenenti P, Perna A, Iliev IP, Gaspari F, Ferrari S, Stucchi N, Bossi A, Trevisan R, Remuzzi G, Parvanova A. Glomerular resistances predict long-term GFR decline in type 2 diabetic patients without overt nephropathy: a longitudinal subgroup analysis of the DEMAND trial. Acta Diabetol. 2022 Mar;59(3):309-317. doi: 10.1007/s00592-021-01804-9. Epub 2021 Oct 14.
PubMed 34648087Ruggenenti P, Porrini EL, Gaspari F, Motterlini N, Cannata A, Carrara F, Cella C, Ferrari S, Stucchi N, Parvanova A, Iliev I, Dodesini AR, Trevisan R, Bossi A, Zaletel J, Remuzzi G; GFR Study Investigators. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care. 2012 Oct;35(10):2061-8. doi: 10.2337/dc11-2189. Epub 2012 Jul 6.
PubMed 22773704Ruggenenti P, Lauria G, Iliev IP, Fassi A, Ilieva AP, Rota S, Chiurchiu C, Barlovic DP, Sghirlanzoni A, Lombardi R, Penza P, Cavaletti G, Piatti ML, Frigeni B, Filipponi M, Rubis N, Noris G, Motterlini N, Ene-Iordache B, Gaspari F, Perna A, Zaletel J, Bossi A, Dodesini AR, Trevisan R, Remuzzi G; DEMAND Study Investigators. Effects of manidipine and delapril in hypertensive patients with type 2 diabetes mellitus: the delapril and manidipine for nephroprotection in diabetes (DEMAND) randomized clinical trial. Hypertension. 2011 Nov;58(5):776-83. doi: 10.1161/HYPERTENSIONAHA.111.174474. Epub 2011 Sep 19.
PubMed 21931073
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Prospective, Double-blind Study to Evaluate the Nephroprotective Effect of Delapril Alone or Combined With Manidipine in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT00157586
- Acronym / sponsor ID
- DM/PR/7401/005/00
- Conditions
- Type 2 Diabetes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 342 participants
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- Feb 2002
- Study completion
- Jun 2008
- First posted
- 12 Sep 2005 (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.
Diabetes mellitus is one of the most common diseases globally, and is considered epidemic in many developed and newly industrialized nations. Diabetes mellitus represents the single largest cause of end-stage renal disease in the U.S. and Europe. At the same time, the primary cause of early death in diabetic patients are cardiovascular complications. Experimental and clinical studies found that angiotensin converting enzyme inhibitors (ACEi) and calcium channel blockers (CCBs) have a specific renoprotective effect and that this effect can be magnified when the two drugs are used in combination. To formally test this hypothesis we designed the Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND) study, a prospective, randomized, double blind trial aimed to compare the effect of 3 years treatment with the ACEi Delapril (30 mg/day), alone or combined to the CCB Manidipine (10 mg/day), versus conventional (non ACEi, non CCB) therapy on the rate of renal function loss and on the incidence of major cardiovascular events in 342 normo- and micro-albuminuric hypertensive type 2 diabetic patients.
Detailed description
INTRODUCTION Optimal blood pressure, glycemic and lipid control are of utmost importance to minimize the incidence and the progression of chronic renal and cardiovascular complications in patients with diabetes mellitus type 2. Whether angiotensin converting enzyme (ACE) inhibitors alone or combined to calcium channel blockers (CCB) may further reduce the incidence and progression of chronic complications is worth investigating.
AIMS The primary aim of this study is to assess whether at comparable levels of optimal blood pressure and metabolic control, the ACE inhibitor delapril alone or in combination with the dihydropyridine CCB manidipine slow the rate of glomerular filtration rate (GFR) decline as compared with placebo plus conventional antihypertensive therapy in patients with diabetes mellitus type 2 and hypertension. The secondary aim of this study is to assess the effects of delapril and manidipine on the incidence of major cardiovascular events (acute myocardial infarction, ictus or stroke, heart failure requiring hospitalization, revascularization, amputation and cardiovascular mortality).
STUDY POPULATION 342 hypertensive type 2 diabetes patients with normo- or micro-albuminuria. STUDY DESIGN This is a multicenter, prospective, randomized, double-blind, placebo-controlled study. After a 12-week baseline period in which prohibited antihypertensive treatments (ACE inhibitors, angiotensin II receptor antagonists or dihydropyridine calcium channel blockers) will be discontinued, patients will be stratified according to their urinary albumin excretion rate in normo- and micro-albuminuric and then randomized to delapril alone (30 mg/day), delapril (30 mg/day) combined with manidipine (10 mg/day) or placebo given once daily in the morning for at least three years. During the study, systolic and diastolic blood pressure in all treatments groups will be maintained ≤ 120 and 80 mmHg respectively, with fixed doses of study treatments and flexible doses of permitted antihypertensive therapy (diuretics, beta blockers, alfa blockers, centrally acting adrenergic blockers. Blood pressure, blood glucose concentrations and urinary albumin excretion rate will be monitored every three months. Serum lipid concentrations and GFR (estimated with the iohexol plasma clearance) will be measured every six months.
Primary and Secondary Variables. The primary efficacy variable of this study is the rate of GFR decline. The secondary efficacy variable will be the incidence of major cardiovascular events (acute myocardial infarction, ictus or stroke, heart failure requiring hospitalization, revascularization, amputation and cardiovascular mortality).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 40 years
- History of diabetes mellitus type 2 for at least three months with stable antidiabetic treatment
- Systolic and/or diastolic blood pressure ≥ 135 or 85 mmHg, respectively. In alternative, antihypertensive therapy regardless of blood pressure values
- Serum creatinine ≤ 1.5 mg/dL
- Urinary albumin excretion rate < 200 µg/min
Key exclusion criteria (25 listed)
- Clinical or histological evidence of non-diabetic renal disease, including vascular disease of the kidney, obstructive uropathy, prostatic hypertrophy or incomplete bladder emptying
- Transplanted kidney
- Moderate to severe chronic heart failure (III-IV stage according to the NYHA classification).
- Cerebral hemorrhage, stroke or transient ischemic attack within three months prior to the trial enrolment
- Myocardial infarction within three months prior to the trial enrolment
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 |
|---|---|---|
| Delapril, Delapril-Manidipine Fixed combination | Drug | – |
Primary outcome
The rate of decline of glomerular filtration rate (GFR).GFR is measured at baseline,and at 6,12,18,24,30 and 36 months after randomization
1 secondary outcome
Major cardiovascular events
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 9 Apr 2015.
- Derived from this study: PubMed 34648087Carrara F, Ruggenenti P, Perna A, Iliev IP, Gaspari F, Ferrari S, Stucchi N, Bossi A, Trevisan R, Remuzzi G, Parvanova A. Glomerular resistances predict long-term GFR decline in type 2 diabetic patients without overt nephropathy: a longitudinal subgroup analysis of the DEMAND trial. Acta Diabetol. 2022 Mar;59(3):309-317. doi: 10.1007/s00592-021-01804-9. Epub 2021 Oct 14.
- Derived from this study: PubMed 22773704Ruggenenti P, Porrini EL, Gaspari F, Motterlini N, Cannata A, Carrara F, Cella C, Ferrari S, Stucchi N, Parvanova A, Iliev I, Dodesini AR, Trevisan R, Bossi A, Zaletel J, Remuzzi G; GFR Study Investigators. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care. 2012 Oct;35(10):2061-8. doi: 10.2337/dc11-2189. Epub 2012 Jul 6.
- Derived from this study: PubMed 21931073Ruggenenti P, Lauria G, Iliev IP, Fassi A, Ilieva AP, Rota S, Chiurchiu C, Barlovic DP, Sghirlanzoni A, Lombardi R, Penza P, Cavaletti G, Piatti ML, Frigeni B, Filipponi M, Rubis N, Noris G, Motterlini N, Ene-Iordache B, Gaspari F, Perna A, Zaletel J, Bossi A, Dodesini AR, Trevisan R, Remuzzi G; DEMAND Study Investigators. Effects of manidipine and delapril in hypertensive patients with type 2 diabetes mellitus: the delapril and manidipine for nephroprotection in diabetes (DEMAND) randomized clinical trial. Hypertension. 2011 Nov;58(5):776-83. doi: 10.1161/HYPERTENSIONAHA.111.174474. Epub 2011 Sep 19.
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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.
Piero Ruggenenti, MD principal investigator
Mario Negri Institute
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Delapril, Delapril-Manidipine Fixed combination in people with Type 2 Diabetes, run by Mario Negri Institute for Pharmacological Research at 8 sites in 2 countries.
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 6 inclusion and 25 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 9 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Italy, Slovenia. 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 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?
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?
The rate of decline of glomerular filtration rate (GFR).GFR is measured at baseline,and at 6,12,18,24,30 and 36 months after randomization. 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 NCT00157586, which also lists 3 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 9 Apr 2015; AzTrials last refreshed its copy on 8 Nov 2026.