The Modification of Diet in Renal Disease Study

NCT04364113 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: MDRD U01DK035073U01DK035073
• Study Type: interventional
• Target: 840
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Renal Disease

Outcome Measures

Primary Outcomes (1)

• 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

  Up to 4 years

Secondary Outcomes (4)

• Dialysis or kidney transplantation

  3 years

• Death from any cause

  3 years

• Time to kidney failure

  Up to 10 years

• Time to kidney failure or death

  Up to 10 years

Study Arms (8)

Study A Usual Protein Usual Pressure

ACTIVE COMPARATOR

Study A Usual Protein and Usual Pressure

Other: Usual Protein Diet; Drug: Medications needed to maintain usual blood pressure

Study A Usual Protein Low Pressure

EXPERIMENTAL

Study A Usual Protein and Low Pressure

Other: Usual Protein Diet; Drug: Medications needed to maintain low blood pressure

Study A Low Protein Usual Pressure

EXPERIMENTAL

Study A Low Protein and Usual Pressure

Other: Low Protein Diet; Drug: Medications needed to maintain usual blood pressure

Study A Low Protein Low Pressure

EXPERIMENTAL

Study A Low Protein and Low Pressure

Other: Low Protein Diet; Drug: Medications needed to maintain low blood pressure

Study B Low Protein Usual Pressure

ACTIVE COMPARATOR

Study B Low Protein and Usual Pressure

Other: Low Protein Diet; Drug: Medications needed to maintain usual blood pressure

Study B Low Protein Low Pressure

EXPERIMENTAL

Study B Low Protein and Low Pressure

Other: Low Protein Diet; Drug: Medications needed to maintain low blood pressure

Study B Very Low Protein Usual Pressure

EXPERIMENTAL

Study B Very Low Protein and Usual Pressure

Other: Very Low Protein Diet; Drug: Medications needed to maintain usual blood pressure

Study B Very Low Protein Low Pressure

EXPERIMENTAL

Study B Very Low Protein and Low Pressure

Other: Very Low Protein Diet; Drug: Medications needed to maintain low blood pressure

Interventions

Usual Protein Diet OTHER

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

Study A Usual Protein Low Pressure; Study A Usual Protein Usual Pressure

Low Protein Diet OTHER

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

Study A Low Protein Low Pressure; Study A Low Protein Usual Pressure; Study B Low Protein Low Pressure; Study B Low Protein Usual Pressure

Very Low Protein Diet OTHER

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

Study B Very Low Protein Low Pressure; Study B Very Low Protein Usual Pressure

Medications needed to maintain usual blood pressure 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 Usual Pressure; Study A Usual Protein Usual Pressure; Study B Low Protein Usual Pressure; Study B Very Low Protein Usual Pressure

Medications needed to maintain low blood pressure 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 Low Pressure; Study A Usual Protein Low Pressure; Study B Low Protein Low Pressure; Study B Very Low Protein Low Pressure

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• The Cleveland Clinic: collaborator

Related Publications (4)

• 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.

  PMID: 8114857 RESULT

• 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.

  PMID: 10541304 RESULT

• 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.

  PMID: 15738453 RESULT

• 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.

  PMID: 17162142 RESULT

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Diet, Protein-Restricted

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Gerald J Beck

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 27, 2020
• Study Start: January 1, 1989
• Primary Completion: January 31, 1993
• Study Completion: December 31, 2000
• Last Updated: April 27, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR, ANALYTIC CODE