search
Back to results

The Modification of Diet in Renal Disease Study (MDRD)

Primary Purpose

Chronic Renal Disease

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Usual Protein Diet
Low Protein Diet
Very Low Protein Diet
Medications needed to maintain usual blood pressure
Medications needed to maintain low blood pressure
Sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Renal Disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm Type

    Active Comparator

    Experimental

    Experimental

    Experimental

    Active Comparator

    Experimental

    Experimental

    Experimental

    Arm Label

    Study A Usual Protein Usual Pressure

    Study A Usual Protein Low Pressure

    Study A Low Protein Usual Pressure

    Study A Low Protein Low Pressure

    Study B Low Protein Usual Pressure

    Study B Low Protein Low Pressure

    Study B Very Low Protein Usual Pressure

    Study B Very Low Protein Low Pressure

    Arm Description

    Study A Usual Protein and Usual Pressure

    Study A Usual Protein and Low Pressure

    Study A Low Protein and Usual Pressure

    Study A Low Protein and Low Pressure

    Study B Low Protein and Usual Pressure

    Study B Low Protein and Low Pressure

    Study B Very Low Protein and Usual Pressure

    Study B Very Low Protein and Low Pressure

    Outcomes

    Primary Outcome Measures

    Change in GFR slope
    Slopes will be calculated on the basis of the final baseline GFR and all follow-up values without adjustment for body surface area

    Secondary Outcome Measures

    Dialysis or kidney transplantation
    Time to first dialysis or kidney transplantation
    Death from any cause
    Time to death from any cause
    Time to kidney failure
    The onset of kidney failure was ascertained from the US Renal Data System (USRDS) and included starting dialysis or undergoing kidney transplant
    Time to kidney failure or death
    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

    Full Information

    First Posted
    April 23, 2020
    Last Updated
    April 23, 2020
    Sponsor
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    Collaborators
    The Cleveland Clinic
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT04364113
    Brief Title
    The Modification of Diet in Renal Disease Study
    Acronym
    MDRD
    Official Title
    The Modification of Diet in Renal Disease Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    January 1, 1989 (Actual)
    Primary Completion Date
    January 31, 1993 (Actual)
    Study Completion Date
    December 31, 2000 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    Collaborators
    The Cleveland Clinic

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The Modification of Diet in Renal Disease Trial is a multicenter randomized clinical trial for men and women aged 18-70 years with chronic renal disease who are not on dialysis and who have not had a kidney transplant. Study participants are randomized in a 2 × 2 factorial design to diets containing different amounts of protein and phosphorus and to two levels of blood pressure control. The prescribed modifications differ depending on the level of a patient's kidney function. The primary outcome variable to compare diet or blood pressure groups is each patient's slope (or the change) in glomerular filtration rate (GFR) with time.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Renal Disease

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Factorial Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    840 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Study A Usual Protein Usual Pressure
    Arm Type
    Active Comparator
    Arm Description
    Study A Usual Protein and Usual Pressure
    Arm Title
    Study A Usual Protein Low Pressure
    Arm Type
    Experimental
    Arm Description
    Study A Usual Protein and Low Pressure
    Arm Title
    Study A Low Protein Usual Pressure
    Arm Type
    Experimental
    Arm Description
    Study A Low Protein and Usual Pressure
    Arm Title
    Study A Low Protein Low Pressure
    Arm Type
    Experimental
    Arm Description
    Study A Low Protein and Low Pressure
    Arm Title
    Study B Low Protein Usual Pressure
    Arm Type
    Active Comparator
    Arm Description
    Study B Low Protein and Usual Pressure
    Arm Title
    Study B Low Protein Low Pressure
    Arm Type
    Experimental
    Arm Description
    Study B Low Protein and Low Pressure
    Arm Title
    Study B Very Low Protein Usual Pressure
    Arm Type
    Experimental
    Arm Description
    Study B Very Low Protein and Usual Pressure
    Arm Title
    Study B Very Low Protein Low Pressure
    Arm Type
    Experimental
    Arm Description
    Study B Very Low Protein and Low Pressure
    Intervention Type
    Other
    Intervention Name(s)
    Usual Protein Diet
    Intervention Description
    The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus
    Intervention Type
    Other
    Intervention Name(s)
    Low Protein Diet
    Intervention Description
    The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus
    Intervention Type
    Other
    Intervention Name(s)
    Very Low Protein Diet
    Intervention Description
    The very low protein diet contains 0.28 g/kg/day or protein, mg/kg/day of Phosphorus and a keto acid mixture.
    Intervention Type
    Drug
    Intervention Name(s)
    Medications needed to maintain usual blood pressure
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Medications needed to maintain low blood pressure
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Change in GFR slope
    Description
    Slopes will be calculated on the basis of the final baseline GFR and all follow-up values without adjustment for body surface area
    Time Frame
    Up to 4 years
    Secondary Outcome Measure Information:
    Title
    Dialysis or kidney transplantation
    Description
    Time to first dialysis or kidney transplantation
    Time Frame
    3 years
    Title
    Death from any cause
    Description
    Time to death from any cause
    Time Frame
    3 years
    Title
    Time to kidney failure
    Description
    The onset of kidney failure was ascertained from the US Renal Data System (USRDS) and included starting dialysis or undergoing kidney transplant
    Time Frame
    Up to 10 years
    Title
    Time to kidney failure or death
    Description
    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
    Time Frame
    Up to 10 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Gerald J Beck
    Organizational Affiliation
    The Cleveland Clinic
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Data and samples are available at the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) Central Repository
    IPD Sharing URL
    https://repository.niddk.nih.gov/studies/mdrd/?query=mdrd
    Citations:
    PubMed Identifier
    8114857
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    10541304
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    15738453
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    17162142
    Citation
    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.
    Results Reference
    result

    Learn more about this trial

    The Modification of Diet in Renal Disease Study

    We'll reach out to this number within 24 hrs