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The Modification of Diet in Renal Disease Study

Phase 3
Completed
Conditions
Chronic Renal Disease
Interventions
Other: Low Protein Diet
Other: Usual Protein Diet
Other: Very Low Protein Diet
Drug: Medications needed to maintain low blood pressure
Drug: Medications needed to maintain usual blood pressure
Registration Number
NCT04364113
Lead Sponsor
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
840
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 & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Study B Low Protein Usual PressureLow Protein DietStudy B Low Protein and Usual Pressure
Study A Usual Protein Low PressureUsual Protein DietStudy A Usual Protein and Low Pressure
Study A Usual Protein Low PressureMedications needed to maintain low blood pressureStudy A Usual Protein and Low Pressure
Study A Low Protein Low PressureMedications needed to maintain low blood pressureStudy A Low Protein and Low Pressure
Study A Low Protein Usual PressureLow Protein DietStudy A Low Protein and Usual Pressure
Study A Usual Protein Usual PressureUsual Protein DietStudy A Usual Protein and Usual Pressure
Study A Usual Protein Usual PressureMedications needed to maintain usual blood pressureStudy A Usual Protein and Usual Pressure
Study A Low Protein Usual PressureMedications needed to maintain usual blood pressureStudy A Low Protein and Usual Pressure
Study A Low Protein Low PressureLow Protein DietStudy A Low Protein and Low Pressure
Study B Low Protein Usual PressureMedications needed to maintain usual blood pressureStudy B Low Protein and Usual Pressure
Study B Low Protein Low PressureLow Protein DietStudy B Low Protein and Low Pressure
Study B Very Low Protein Usual PressureVery Low Protein DietStudy B Very Low Protein and Usual Pressure
Study B Low Protein Low PressureMedications needed to maintain low blood pressureStudy B Low Protein and Low Pressure
Study B Very Low Protein Usual PressureMedications needed to maintain usual blood pressureStudy B Very Low Protein and Usual Pressure
Study B Very Low Protein Low PressureMedications needed to maintain low blood pressureStudy B Very Low Protein and Low Pressure
Study B Very Low Protein Low PressureVery Low Protein DietStudy B Very Low Protein and Low Pressure
Primary Outcome Measures
NameTimeMethod
Change in GFR slopeUp 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
NameTimeMethod
Time to kidney failure or deathUp 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

Dialysis or kidney transplantation3 years

Time to first dialysis or kidney transplantation

Death from any cause3 years

Time to death from any cause

Time to kidney failureUp 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

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