The Modification of Diet in Renal Disease Study

NCT ID: NCT04364113

Last Updated: 2020-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 840 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1989-01-01
• Study Completion Date: 2000-12-31

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.

Conditions

Chronic Renal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study A Usual Protein Usual Pressure

Study A Usual Protein and Usual Pressure

Group Type: ACTIVE_COMPARATOR

Usual Protein Diet

Intervention Type: OTHER

The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus

Medications needed to maintain usual blood pressure

Intervention Type: DRUG

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.

Study A Usual Protein Low Pressure

Study A Usual Protein and Low Pressure

Group Type: EXPERIMENTAL

Usual Protein Diet

Intervention Type: OTHER

The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus

Medications needed to maintain low blood pressure

Intervention Type: DRUG

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.

Study A Low Protein Usual Pressure

Study A Low Protein and Usual Pressure

Group Type: EXPERIMENTAL

Low Protein Diet

Intervention Type: OTHER

The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus

Medications needed to maintain usual blood pressure

Intervention Type: DRUG

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.

Study A Low Protein Low Pressure

Study A Low Protein and Low Pressure

Group Type: EXPERIMENTAL

Low Protein Diet

Intervention Type: OTHER

The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus

Medications needed to maintain low blood pressure

Intervention Type: DRUG

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.

Study B Low Protein Usual Pressure

Study B Low Protein and Usual Pressure

Group Type: ACTIVE_COMPARATOR

Low Protein Diet

Intervention Type: OTHER

The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus

Medications needed to maintain usual blood pressure

Intervention Type: DRUG

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.

Study B Low Protein Low Pressure

Study B Low Protein and Low Pressure

Group Type: EXPERIMENTAL

Low Protein Diet

Intervention Type: OTHER

The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus

Medications needed to maintain low blood pressure

Intervention Type: DRUG

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.

Study B Very Low Protein Usual Pressure

Study B Very Low Protein and Usual Pressure

Group Type: EXPERIMENTAL

Very Low Protein Diet

Intervention Type: OTHER

The very low protein diet contains 0.28 g/kg/day or protein, mg/kg/day of Phosphorus and a keto acid mixture.

Medications needed to maintain usual blood pressure

Intervention Type: DRUG

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.

Study B Very Low Protein Low Pressure

Study B Very Low Protein and Low Pressure

Group Type: EXPERIMENTAL

Very Low Protein Diet

Intervention Type: OTHER

The very low protein diet contains 0.28 g/kg/day or protein, mg/kg/day of Phosphorus and a keto acid mixture.

Medications needed to maintain low blood pressure

Intervention Type: DRUG

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.

Interventions

Usual Protein Diet

The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus

Intervention Type: OTHER

Low Protein Diet

The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus

Intervention Type: 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.

Intervention Type: OTHER

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.

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gerald J Beck

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

References

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.

Reference Type: RESULT

PMID: 8114857 (View on PubMed)

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.

Reference Type: RESULT

PMID: 10541304 (View on PubMed)

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.

Reference Type: RESULT

PMID: 15738453 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17162142 (View on PubMed)

Other Identifiers

U01DK035073

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MDRD U01DK035073

Identifier Type: -

Identifier Source: org_study_id