Chronic Renal DiseasePhase 3MDRDNCT04364113
The Modification of Diet in Renal Disease Study
A Phase 3 study testing Usual Protein Diet, Low Protein Diet and Very Low Protein Diet in people with Chronic Renal Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Renal Disease
- What is being tested?
- Usual Protein Diet, Low Protein Diet and Very Low Protein Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 840 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 1989to 31 Dec 2000
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
About this study
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.
Read the 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
- Being tested
- Usual Protein Diet, Low Protein Diet, Very Low Protein Diet, Medications needed to maintain usual blood pressure, Medications needed to maintain low blood pressure
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Usual Protein DietOther
The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus
Low Protein DietOther
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus
Very Low Protein DietOther
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 pressureDrug
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.
Medications needed to maintain low blood pressureDrug
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 group | Role | What they receive |
|---|---|---|
| Study A Usual Protein Usual Pressure | Active comparator | Study A Usual Protein and Usual Pressure Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Other: Very Low Protein Diet; Drug: Medications needed to maintain low blood pressure |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 4 years
Secondary outcomes (4)
Dialysis or kidney transplantation
Time to first dialysis or kidney transplantation
Measured: 3 years
Death from any cause
Time to death from any cause
Measured: 3 years
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
Measured: Up to 10 years
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
Measured: Up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2020
- Study start1 Jan 1989
- Primary completion31 Jan 1993
- Study completion31 Dec 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Renal DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 840 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- The Cleveland Clinic
- Responsible party
- Sponsor
- Investigators
- Gerald J Beck, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04364113
- Sponsor's protocol ID
- MDRD U01DK035073
- Other IDs
- U01DK035073
- Acronym
- MDRD
- Status last verified
- Apr 2020
- First submitted
- 23 Apr 2020
- Last updated
- 27 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data and samples are available at the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) Central Repository
Publications
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.
PubMed 8114857Levey 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.
PubMed 10541304Sarnak 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.
PubMed 15738453Levey 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.
PubMed 17162142
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Modification of Diet in Renal Disease Study
- ClinicalTrials.gov ID
- NCT04364113
- Acronym / sponsor ID
- MDRD / MDRD U01DK035073
- Conditions
- Chronic Renal Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 840 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- The Cleveland Clinic
- Study start
- 1 Jan 1989 (actual)
- Primary completion
- 31 Jan 1993 (actual)
- Study completion
- 31 Dec 2000 (actual)
- First posted
- 27 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Study A Usual Protein Usual Pressure | Active comparator | Other: Usual Protein Diet, Drug: Medications needed to maintain usual blood pressureStudy A Usual Protein and Usual Pressure |
| Study A Usual Protein Low Pressure | Experimental | Other: Usual Protein Diet, Drug: Medications needed to maintain low blood pressureStudy A Usual Protein and Low Pressure |
| Study A Low Protein Usual Pressure | Experimental | Other: Low Protein Diet, Drug: Medications needed to maintain usual blood pressureStudy A Low Protein and Usual Pressure |
| Study A Low Protein Low Pressure | Experimental | Other: Low Protein Diet, Drug: Medications needed to maintain low blood pressureStudy A Low Protein and Low Pressure |
| Study B Low Protein Usual Pressure | Active comparator | Other: Low Protein Diet, Drug: Medications needed to maintain usual blood pressureStudy B Low Protein and Usual Pressure |
| Study B Low Protein Low Pressure | Experimental | Other: Low Protein Diet, Drug: Medications needed to maintain low blood pressureStudy B Low Protein and Low Pressure |
| Study B Very Low Protein Usual Pressure | Experimental | Other: Very Low Protein Diet, Drug: Medications needed to maintain usual blood pressureStudy B Very Low Protein and Usual Pressure |
| Study B Very Low Protein Low Pressure | Experimental | Other: Very Low Protein Diet, Drug: Medications needed to maintain low blood pressureStudy B Very Low Protein and Low Pressure |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Usual Protein DietThe usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus | Other | Study A Usual Protein Low Pressure, Study A Usual Protein Usual Pressure |
| Low Protein DietThe low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus | Other | 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 DietThe very low protein diet contains 0.28 g/kg/day or protein, mg/kg/day of Phosphorus and a keto acid mixture. | Other | Study B Very Low Protein Low Pressure, Study B Very Low Protein Usual Pressure |
| Medications needed to maintain usual blood pressureThe 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. | Drug | 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 pressureThe 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. | Drug | 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 |
Primary outcome
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
4 secondary outcomes
Dialysis or kidney transplantation
Time frame: 3 years
Death from any cause
Time frame: 3 years
Time to kidney failure
Time frame: Up to 10 years
Time to kidney failure or death
Time frame: Up to 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2020.
- Results publication: PubMed 8114857Klahr 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 publication: PubMed 10541304Levey 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 publication: PubMed 15738453Sarnak 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 publication: PubMed 17162142Levey 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.
- Individual participant dataSharing planned: Yes. Data and samples are available at the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) Central Repository
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerald J Beck principal investigator
The Cleveland Clinic
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Usual Protein Diet, Low Protein Diet and Very Low Protein Diet in people with Chronic Renal Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in GFR slope (time frame: Up to 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04364113, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2020.