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The Modification of Diet in Renal Disease Study (MDRD)

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ClinicalTrials.gov Identifier: NCT04364113
Recruitment Status : Completed
First Posted : April 27, 2020
Last Update Posted : April 27, 2020
Sponsor:
Collaborator:
The Cleveland Clinic
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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.

Condition or disease Intervention/treatment Phase
Chronic Renal Disease Other: Usual Protein Diet Other: Low Protein Diet Other: Very Low Protein Diet Drug: Medications needed to maintain usual blood pressure Drug: Medications needed to maintain low blood pressure Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 840 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Modification of Diet in Renal Disease Study
Actual Study Start Date : January 1, 1989
Actual Primary Completion Date : January 31, 1993
Actual Study Completion Date : December 31, 2000

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
Active Comparator: Study A Usual Protein Usual Pressure
Study A Usual Protein and Usual Pressure
Other: Usual Protein Diet
The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus

Drug: Medications needed to maintain usual blood 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.

Experimental: Study A Usual Protein Low Pressure
Study A Usual Protein and Low Pressure
Other: Usual Protein Diet
The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus

Drug: Medications needed to maintain low blood 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.

Experimental: Study A Low Protein Usual Pressure
Study A Low Protein and Usual Pressure
Other: Low Protein Diet
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus

Drug: Medications needed to maintain usual blood 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.

Experimental: Study A Low Protein Low Pressure
Study A Low Protein and Low Pressure
Other: Low Protein Diet
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus

Drug: Medications needed to maintain low blood 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.

Active Comparator: Study B Low Protein Usual Pressure
Study B Low Protein and Usual Pressure
Other: Low Protein Diet
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus

Drug: Medications needed to maintain usual blood 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.

Experimental: Study B Low Protein Low Pressure
Study B Low Protein and Low Pressure
Other: Low Protein Diet
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus

Drug: Medications needed to maintain low blood 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.

Experimental: Study B Very Low Protein Usual Pressure
Study B Very Low Protein and Usual Pressure
Other: Very Low Protein Diet
The very low protein diet contains 0.28 g/kg/day or protein, mg/kg/day of Phosphorus and a keto acid mixture.

Drug: Medications needed to maintain usual blood 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.

Experimental: Study B Very Low Protein Low Pressure
Study B Very Low Protein and Low Pressure
Other: Very Low Protein Diet
The very low protein diet contains 0.28 g/kg/day or protein, mg/kg/day of Phosphorus and a keto acid mixture.

Drug: Medications needed to maintain low blood 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.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Dialysis or kidney transplantation [ Time Frame: 3 years ]
    Time to first dialysis or kidney transplantation

  2. Death from any cause [ Time Frame: 3 years ]
    Time to death from any cause

  3. 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

  4. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04364113


Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
The Cleveland Clinic
Investigators
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Principal Investigator: Gerald J Beck The Cleveland Clinic
Publications of Results:
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT04364113    
Other Study ID Numbers: MDRD U01DK035073
U01DK035073 ( U.S. NIH Grant/Contract )
First Posted: April 27, 2020    Key Record Dates
Last Update Posted: April 27, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data and samples are available at the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) Central Repository
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Analytic Code
URL: https://repository.niddk.nih.gov/studies/mdrd/?query=mdrd

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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
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency
Benzocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents