- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04364113
The Modification of Diet in Renal Disease Study (MDRD)
Study Overview
Status
Conditions
Detailed Description
Selection of patients is conducted in two periods: a screening period for initial determination of eligibility and a 3-month baseline period. The baseline period is used to instruct patients about study procedures; to assess GFR and dietary protein intake; and to control blood pressure according to standard medical practice. GFR, dietary protein, and urinary protein must meet the eligibility criteria at the end of the baseline period before an individual can be randomized.
Two different strata or studies are used depending on the level of an individual's GFR at the end of the baseline period. Study A is for individuals with a GFR from 25 to 55 ml/min/1.73 m^2 and a usual dietary protein intake of at least 0.90 g/kg/day, where kg are standard body weight. Study B is for persons with a baseline GFR from 13 to 24 ml/min/1.73 m^2 and no specification of protein intake.
Individuals who are randomized in the trial are prescribed one of three diets and one of two target mean arterial blood pressure goals (MAP). MAP is a weighted average of the diastolic and systolic blood pressures (two-thirds diastolic plus one-third systolic). The goals depend on the person's age. The moderate goal of 107 mm Hg is equivalent to a blood pressure of 140/90 mm Hg, the usual limits of normal blood pressure. The low-MAP goal of 92 mm Hg is a more strict level of control than usually achieved, equivalent to, for example, 125/75 mm Hg.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Increased serum creatinine: Men: 1.4-7.0 mg/dl, Women: 1.2-7.0 mg/dl, or other objective evidence of kidney disease
- Mean arterial blood pressure <=125 mm Hg
- GFR 13-55 ml/min/1.73 m^2
- Urinary protein excretion <10 g/day
- Protein intake >0.90 g/kg/day if GFR 25-55 ml/min/1.73 m^2
Exclusion Criteria:
- Insulin-dependent diabetes or fasting serum glucose >200 mg/dl
- Patient on dialysis
- Kidney transplant recipient
- Lactating or pregnant woman or woman planning to become pregnant within the time frame of the study
- Doubtful compliance
- Body weight <80% or >160% of standard body weight
- Serum albumin <3.0 g/dl
- Selected renal disorders: Upper or lower urinary tract obstruction, Renal artery stenosis, Branched or staghorn calculi, Cystinuria
- Serious medical conditions: Malignancy (excluding skin cancer) within 1 year, Heart failure, New York Heart Association class 3 or 4, Lung disease, Liver disease, Gastrointestinal disease, Chronic systemic infections, including AIDS, Collagen vascular disease (other than rheumatoid arthritis), Frequent hospitalizations or disability
- Drugs: Immunosuppressive agents, Corticosteroids in excess of replacement dosage for 2 months per year or more, Gold or penicillamine within past month, Salicylates: more than 20 tablets per week, Other nonsteroidal antiinflammatory agents more than 3 times per week in past 2 months, Investigational drugs
- Allergy to iothalamate or iodine
- Inability or unwillingness to give consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Study A Usual Protein Usual Pressure
Study A Usual Protein and Usual Pressure
|
The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus
The MAP goal for the usual blood pressure group is <=107 mm Hg for ages 18-60 and <=113 for ages 61+.
Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values.
The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.
|
Experimental: Study A Usual Protein Low Pressure
Study A Usual Protein and Low Pressure
|
The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus
The MAP goal for the low blood pressure group is <=92 mm Hg for ages 18-60 and <=98 for ages 61+.
Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values.
The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.
|
Experimental: Study A Low Protein Usual Pressure
Study A Low Protein and Usual Pressure
|
The MAP goal for the usual blood pressure group is <=107 mm Hg for ages 18-60 and <=113 for ages 61+.
Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values.
The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus
|
Experimental: Study A Low Protein Low Pressure
Study A Low Protein and Low Pressure
|
The MAP goal for the low blood pressure group is <=92 mm Hg for ages 18-60 and <=98 for ages 61+.
Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values.
The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus
|
Active Comparator: Study B Low Protein Usual Pressure
Study B Low Protein and Usual Pressure
|
The MAP goal for the usual blood pressure group is <=107 mm Hg for ages 18-60 and <=113 for ages 61+.
Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values.
The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus
|
Experimental: Study B Low Protein Low Pressure
Study B Low Protein and Low Pressure
|
The MAP goal for the low blood pressure group is <=92 mm Hg for ages 18-60 and <=98 for ages 61+.
Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values.
The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus
|
Experimental: Study B Very Low Protein Usual Pressure
Study B Very Low Protein and Usual Pressure
|
The MAP goal for the usual blood pressure group is <=107 mm Hg for ages 18-60 and <=113 for ages 61+.
Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values.
The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.
The very low protein diet contains 0.28 g/kg/day or protein, mg/kg/day of Phosphorus and a keto acid mixture.
|
Experimental: Study B Very Low Protein Low Pressure
Study B Very Low Protein and Low Pressure
|
The MAP goal for the low blood pressure group is <=92 mm Hg for ages 18-60 and <=98 for ages 61+.
Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values.
The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.
The very low protein diet contains 0.28 g/kg/day or protein, mg/kg/day of Phosphorus and a keto acid mixture.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in GFR slope
Time Frame: Up to 4 years
|
Slopes will be calculated on the basis of the final baseline GFR and all follow-up values without adjustment for body surface area
|
Up to 4 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dialysis or kidney transplantation
Time Frame: 3 years
|
Time to first dialysis or kidney transplantation
|
3 years
|
Death from any cause
Time Frame: 3 years
|
Time to death from any cause
|
3 years
|
Time to kidney failure
Time Frame: Up to 10 years
|
The onset of kidney failure was ascertained from the US Renal Data System (USRDS) and included starting dialysis or undergoing kidney transplant
|
Up to 10 years
|
Time to kidney failure or death
Time Frame: Up to 10 years
|
The onset of kidney failure was ascertained from the US Renal Data System (USRDS) and included starting dialysis or undergoing kidney transplant.
Data for death were obtained from the National Death Index
|
Up to 10 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Gerald J Beck, The Cleveland Clinic
Publications and helpful links
General Publications
- Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994 Mar 31;330(13):877-84. doi: 10.1056/NEJM199403313301301.
- Levey AS, Greene T, Beck GJ, Caggiula AW, Kusek JW, Hunsicker LG, Klahr S. Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD study shown? Modification of Diet in Renal Disease Study group. J Am Soc Nephrol. 1999 Nov;10(11):2426-39. doi: 10.1681/ASN.V10112426.
- Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ, Levey AS. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study. Ann Intern Med. 2005 Mar 1;142(5):342-51. doi: 10.7326/0003-4819-142-5-200503010-00009.
- Levey AS, Greene T, Sarnak MJ, Wang X, Beck GJ, Kusek JW, Collins AJ, Kopple JD. Effect of dietary protein restriction on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am J Kidney Dis. 2006 Dec;48(6):879-88. doi: 10.1053/j.ajkd.2006.08.023.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MDRD U01DK035073
- U01DK035073 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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