NCT00157586

Brief 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. 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
342

participants targeted

Target at P25-P50 for phase_3 type-2-diabetes

Timeline
Completed

Started Feb 2002

Longer than P75 for phase_3 type-2-diabetes

Geographic Reach
2 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2002

Completed
3.6 years until next milestone

First Submitted

Initial submission to the registry

September 8, 2005

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 12, 2005

Completed
2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2008

Completed
Last Updated

April 9, 2015

Status Verified

March 1, 2006

First QC Date

September 8, 2005

Last Update Submit

April 8, 2015

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

  • 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

Interventions

Delapril, Delapril-Manidipine Fixed combinationDRUG

Eligibility Criteria

Age40 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • 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
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Hospital "Ospedali Riuniti di Bergamo" - Diabetologic Unit

Bergamo, Bergamo, 24128, Italy

Location

ASL of Ponte San Pietro - Diabetologic Unit

Ponte San Pietro, Bergamo, 24036, Italy

Location

Clinical Research Center for Rare Diseases

Ranica, Bergamo, 24020, Italy

Location

Hospital of Romano di Lombardia - Diabetologic Unit

Romano di Lombardia, Bergamo, 24058, Italy

Location

Hospital " Bolognini " - Medicine Unit

Seriate, Bergamo, 24068, Italy

Location

Hospital " Treviglio Caravaggio" - Diabetologic Unit

Treviglio, Bergamo, 24128, Italy

Location

Humanitas Institute - Endocrinology and Diabetologic Unit

Rozzano, Milano, 20089, Italy

Location

Department of Endocrinolgy, Diabetes and Metabolic Disease - University Medical Center

Ljubljana, Ljubljana, Slovenia

Location

Related Publications (3)

  • 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.

    PMID: 34648087DERIVED

  • Ruggenenti 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.

    PMID: 22773704DERIVED

  • Ruggenenti 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.

    PMID: 21931073DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

delapril

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Piero Ruggenenti, MD

    Mario Negri Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 8, 2005

First Posted

September 12, 2005

Study Start

February 1, 2002

Study Completion

June 1, 2008

Last Updated

April 9, 2015

Record last verified: 2006-03

Locations

IT(7)SL(1)