CKD Stage 4K-DDDNCT03415074
Could Ketoanalogue-supplemented Low Protein Diet Defer Dialysis in Advanced Diabetic Kidney Disease? (K-DDD)
A study testing Protein restriction in people with CKD Stage 4, run by Anemia Working Group Romania at 1 site in Romania.
Trial summary
This is a prospective single center open label randomized controlled trial aiming to assess the effectiveness and safety of a low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (sLPD) as compared to a mild protein restriction (0.8 g/kg-day, MPD) in reducing… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- CKD Stage 4
- What is being tested?
- Protein restriction
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteRomania
- Study dates
- 1 Oct 2019to 31 Mar 2023
- Phase
- Interventional
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diabetic patients
- CKD stage 4+ (estimated GFR using the Modification of Diet in Renal Disease 4-variable, MDRD4, formula <30 mL/min per year)
- stable renal function (historical reduction of eGFR of < 10 ml/min-year)
- proteinuria > 3g/g creatininuria
- good nutritional status (SGA A)
Who cannot join
- evidence of active kidney disease (except proteinuria)
- indication for etiological or pathogenic treatment
- poor control of diabetes (HbA1c >8%)
- uncontrolled high blood pressure (≥155/85 mmHg)
- significant co-morbidities (heart failure, active liver disease, malabsorption, active infections, inflammatory diseases requiring corticosteroids)
- uremic symptoms (pericarditis, digestive disorders
- or malnutrition (SGA B or C, serum albumin < 3.5 g/dl)
Trial locations and contacts
1 site in 1 country.
Romania1 site, 1 recruiting
- Recruiting
"Dr Carol Davila" Teaching Hospital of Nephrology
Bucharest, 010731
Liliana Garneata, Assoc Prof, +40722619358, lilianagarna@yahoo.com
Carmen Antonia Mocanu, MD, +40723673275, carmen_a9@yahoo.com
About this study
Official title: Ketoanalogue-supplemented Low Protein Diet and Deferring Dialysis in Patients With Severe Proteinuria and Advanced Diabetic Kidney Disease
This is a prospective single center open label randomized controlled trial aiming to assess the effectiveness and safety of a low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (sLPD) as compared to a mild protein restriction (0.8 g/kg-day, MPD) in reducing Chronic Kidney Disease (CKD) progression, with a planned total duration is of 18 months.
Adult diabetic patients with CKD stage 4+ [estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease 4-variable (MDRD4) formula <30 mL/min per year], with stable renal function (historical reduction of eGFR of < 10 ml/min-year) , proteinuria > 3g/g creatininuria and good nutritional status (SGA A) will be enrolled.
Read the detailed description
Adult diabetic patients with Chronic Kidney Disease (CKD) stage 4+ (estimated GFR using the Modification of Diet in Renal Disease 4-variable, MDRD4, formula <30 mL/min per year), with stable renal function (historical reduction of eGFR of < 10 ml/min-year), proteinuria > 3g/g creatininuria and good nutritional status (SGA A) will be enrolled. Patients with evidence of active kidney disease (except proteinuria), with indication of etiological or pathogenic treatment, those with poor control of diabetes (HbA1c >8%), those with uncontrolled high blood pressure (≥155/85 mmHg), those with significant co-morbidities (heart failure, active liver disease, malabsorption, active infections, inflammatory diseases requiring corticosteroids), those with uremic symptoms (pericarditis, digestive disorders ) or malnutrition (SGA B or C, serum albumin < 3.5 g/dl) will be excluded.
Eligible patients will enter a run-in phase (3 mo), when mild protein restriction (0.8g/kg dry ideal bw) will be initiated and compliance will be evaluated twice monthly.
Those who will prove compliant during the run-in phase and still fulfill the selection criteria will be randomized 1:1 (computer-generated numbers) to receive the low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (Ketosteril 1 tb/10 kg dry bw) or to continue the mild protein restriction (0.8 g/kg-day).
The total recommended energy intake is of 30 kcal/kg of ideal dry body weight per day in all patients.
The primary composite endpoint is the need for RRT initiation or a more than 50% reduction in the initial eGFR any time during the assessment phase. The decision to initiate RRT will be made by the Ethical Committee of the Hospital, based on the clinical and laboratory data.
The need for RRT initiation, the quality of life [assessed by the Short Form-36 (SF-36) Questionnaire], the decline in GFR and the correction of metabolic complications of CKD [serum levels of urea, calcium, phosphates, serum parathyroid hormone levels, bicarbonate, potassium] will be secondary efficacy parameters.
Parameters of nutritional status (SGA, anthropometric and biochemical parameters), compliance to the diet, occurrence of any adverse event and the number of withdrawals will be safety variables.
All the parameters will be assessed at baseline, throughout the intervention phase and at end of the study.
- Conditions
- CKD Stage 4
- Being tested
- Protein restriction
- Keywords
- low protein diet, Diabetic Kidney Disease
- Medical subject headings
- Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protein restrictionBehavioural
In both arms the dietary protein intake will be reduced. In the sLPD arm, the protein restriction is more severe and ketoanalogues of the essential aminoacids are offered.
| Study group | Role | What they receive |
|---|---|---|
| Supplemented low protein diet (sLPD) | Active comparator | Protein restriction to a low level (0.6 g/kg-day, mainly vegetarian) + ketoanalogues of essential amino-acids supplementation (Ketosteril 1 tb/10 kg dry bw) Receives: Behavioral: Protein restriction |
| Mild protein restriction diet (MPD) | Active comparator | Mild restriction in dietary protein intake (0.8 g/kg-day) Receives: Behavioral: Protein restriction |
What is being measured
The primary outcome is the main question the study is designed to answer.
CKD progression
Percentage of patients requiring RRT initiation or a more than 50% reduction in the initial eGFR at anytime during the study
Measured: 15 months
Secondary outcomes (18)
Need for renal replacement therapy (RRT)
Percentage of patients requiring RRT during the study
Measured: 15 months
Patients' Quality of life
Patients' Quality of life, assessed by the SF-36 Questionnaire
Measured: at baseline and than every 3 months up to 15 months
Decline in eGFR
Difference between eGFR at any timepoint and the initial eGFR
Measured: monthly up to 15 months
Correction of nitrogen balance
Serum urea
Measured: monthly up to 15 months
Correction of metabolic acidosis
Serum bicarbonate
Measured: monthly up to 15 months
Correction of calcium metabolism abnormalities
Serum calcium
Measured: monthly up to 15 months
Correction of mineral metabolism abnormalities
Serum phosphates
Measured: monthly up to 15 months
Serum level of intact Parathyroid Hormone (iPTH)
iPTH
Measured: monthly up to 15 months
Nutritional status - Subjective Global Assessment (SGA)
SGA
Measured: monthly up to 15 months
Body Mass Index (BMI)
BMI
Measured: monthly up to 15 months
Tricipital Skin Fold (TSF)
TSF
Measured: monthly up to 15 months
Middle arm muscular circumference (MAMC)
MAMC
Measured: monthly up to 15 months
Serum albumin
Serum albumin
Measured: monthly up to 15 months
Serum cholesterol
Serum cholesterol
Measured: monthly up to 15 months
Inflammatory status
Serum C-Reactive Protein (CRP)
Measured: monthly up to 15 months
Compliance to the protein intake
Achieved protein intake (urinary urea excretion, Mitch-Maroni's formula)
Measured: twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and then every 3 months up to 15 months
Compliance to the energy intake
Achieved energy intake (3-days food dairy)
Measured: twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and then every 3 months up to 15 months
Occurence of the adverse events
Occurence of any adverse event
Measured: twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and every 3 months up to 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2018
- Study start1 Oct 2019
- Primary completion30 Sep 2022 (estimated)
- Study completion31 Mar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CKD Stage 4Studies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible patients will enter a run-in phase (3 mo), when mild protein diet (0.8g/kg dry ideal bw) will be initiated and compliance will be evaluated twice monthly. Those who will prove compliant during the run-in phase and still fulfill the selection criteria will be randomized 1:1 (computer-generated numbers) to receive the low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (Ketosteril 1 tb/10 kg dry bw) or to continue the mild protein restriction (0.8 g/kg-day).
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Anemia Working Group Romania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gabriel Mircescu, Prof, Study chair, Carol Davila University of Medicine and Pharmacy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03415074
- Sponsor's protocol ID
- AnemiaWGRomania
- Acronym
- K-DDD
- Status last verified
- Feb 2020
- First submitted
- 30 Dec 2017
- Last updated
- 24 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Unique patient number in the study, biological data; no data to enable patient identification will be provided
Publications
Mihalache A, Garneata L, Mocanu CA, Simionescu TP, Mircescu G. Low-salt low-protein diet and blood pressure control in patients with advanced diabetic kidney disease and heavy proteinuria. Int Urol Nephrol. 2021 Jun;53(6):1197-1207. doi: 10.1007/s11255-020-02717-2. Epub 2021 Jan 2.
PubMed 33389459
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketoanalogue-supplemented Low Protein Diet and Deferring Dialysis in Patients With Severe Proteinuria and Advanced Diabetic Kidney Disease
- ClinicalTrials.gov ID
- NCT03415074
- Acronym / sponsor ID
- K-DDD / AnemiaWGRomania
- Conditions
- CKD Stage 4
- Keywords
- low protein diet, Diabetic Kidney Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Anemia Working Group RomaniaUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 30 Sep 2022 (estimated)
- Study completion
- 31 Mar 2023 (estimated)
- First posted
- 30 Jan 2018 (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.
This is a prospective single center open label randomized controlled trial aiming to assess the effectiveness and safety of a low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (sLPD) as compared to a mild protein restriction (0.8 g/kg-day, MPD) in reducing Chronic Kidney Disease (CKD) progression, with a planned total duration is of 18 months.
Adult diabetic patients with CKD stage 4+ [estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease 4-variable (MDRD4) formula <30 mL/min per year], with stable renal function (historical reduction of eGFR of < 10 ml/min-year) , proteinuria > 3g/g creatininuria and good nutritional status (SGA A) will be enrolled.
Detailed description
Adult diabetic patients with Chronic Kidney Disease (CKD) stage 4+ (estimated GFR using the Modification of Diet in Renal Disease 4-variable, MDRD4, formula <30 mL/min per year), with stable renal function (historical reduction of eGFR of < 10 ml/min-year), proteinuria > 3g/g creatininuria and good nutritional status (SGA A) will be enrolled. Patients with evidence of active kidney disease (except proteinuria), with indication of etiological or pathogenic treatment, those with poor control of diabetes (HbA1c >8%), those with uncontrolled high blood pressure (≥155/85 mmHg), those with significant co-morbidities (heart failure, active liver disease, malabsorption, active infections, inflammatory diseases requiring corticosteroids), those with uremic symptoms (pericarditis, digestive disorders ) or malnutrition (SGA B or C, serum albumin < 3.5 g/dl) will be excluded.
Eligible patients will enter a run-in phase (3 mo), when mild protein restriction (0.8g/kg dry ideal bw) will be initiated and compliance will be evaluated twice monthly.
Those who will prove compliant during the run-in phase and still fulfill the selection criteria will be randomized 1:1 (computer-generated numbers) to receive the low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (Ketosteril 1 tb/10 kg dry bw) or to continue the mild protein restriction (0.8 g/kg-day).
The total recommended energy intake is of 30 kcal/kg of ideal dry body weight per day in all patients.
The primary composite endpoint is the need for RRT initiation or a more than 50% reduction in the initial eGFR any time during the assessment phase. The decision to initiate RRT will be made by the Ethical Committee of the Hospital, based on the clinical and laboratory data.
The need for RRT initiation, the quality of life [assessed by the Short Form-36 (SF-36) Questionnaire], the decline in GFR and the correction of metabolic complications of CKD [serum levels of urea, calcium, phosphates, serum parathyroid hormone levels, bicarbonate, potassium] will be secondary efficacy parameters.
Parameters of nutritional status (SGA, anthropometric and biochemical parameters), compliance to the diet, occurrence of any adverse event and the number of withdrawals will be safety variables.
All the parameters will be assessed at baseline, throughout the intervention phase and at end of the study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Eligible patients will enter a run-in phase (3 mo), when mild protein diet (0.8g/kg dry ideal bw) will be initiated and compliance will be evaluated twice monthly. Those who will prove compliant during the run-in phase and still fulfill the selection criteria will be randomized 1:1 (computer-generated numbers) to receive the low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (Ketosteril 1 tb/10 kg dry bw) or to continue the mild protein restriction (0.8 g/kg-day).
| Arm | Type | Receives |
|---|---|---|
| Supplemented low protein diet (sLPD) | Active comparator | Behavioral: Protein restrictionProtein restriction to a low level (0.6 g/kg-day, mainly vegetarian) + ketoanalogues of essential amino-acids supplementation (Ketosteril 1 tb/10 kg dry bw) |
| Mild protein restriction diet (MPD) | Active comparator | Behavioral: Protein restrictionMild restriction in dietary protein intake (0.8 g/kg-day) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- diabetic patients
- CKD stage 4+ (estimated GFR using the Modification of Diet in Renal Disease 4-variable, MDRD4, formula <30 mL/min per year)
- stable renal function (historical reduction of eGFR of < 10 ml/min-year)
- proteinuria > 3g/g creatininuria
- good nutritional status (SGA A)
Key exclusion criteria (7 listed)
- evidence of active kidney disease (except proteinuria)
- indication for etiological or pathogenic treatment
- poor control of diabetes (HbA1c >8%)
- uncontrolled high blood pressure (≥155/85 mmHg)
- significant co-morbidities (heart failure, active liver disease, malabsorption, active infections, inflammatory diseases requiring corticosteroids)
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 |
|---|---|---|
| Protein restrictionIn both arms the dietary protein intake will be reduced. In the sLPD arm, the protein restriction is more severe and ketoanalogues of the essential aminoacids are offered. | Behavioural | Mild protein restriction diet (MPD), Supplemented low protein diet (sLPD) |
Primary outcome
CKD progression
Time frame: 15 months
Percentage of patients requiring RRT initiation or a more than 50% reduction in the initial eGFR at anytime during the study
18 secondary outcomes
Need for renal replacement therapy (RRT)
Time frame: 15 months
Patients' Quality of life
Time frame: at baseline and than every 3 months up to 15 months
Decline in eGFR
Time frame: monthly up to 15 months
Correction of nitrogen balance
Time frame: monthly up to 15 months
Correction of metabolic acidosis
Time frame: monthly up to 15 months
Correction of calcium metabolism abnormalities
Time frame: monthly up to 15 months
Correction of mineral metabolism abnormalities
Time frame: monthly up to 15 months
Serum level of intact Parathyroid Hormone (iPTH)
Time frame: monthly up to 15 months
Nutritional status - Subjective Global Assessment (SGA)
Time frame: monthly up to 15 months
Body Mass Index (BMI)
Time frame: monthly up to 15 months
Tricipital Skin Fold (TSF)
Time frame: monthly up to 15 months
Middle arm muscular circumference (MAMC)
Time frame: monthly up to 15 months
Serum albumin
Time frame: monthly up to 15 months
Serum cholesterol
Time frame: monthly up to 15 months
Inflammatory status
Time frame: monthly up to 15 months
Compliance to the protein intake
Time frame: twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and then every 3 months up to 15 months
Compliance to the energy intake
Time frame: twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and then every 3 months up to 15 months
Occurence of the adverse events
Time frame: twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and every 3 months up to 15 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2020.
- Derived from this study: PubMed 33389459Mihalache A, Garneata L, Mocanu CA, Simionescu TP, Mircescu G. Low-salt low-protein diet and blood pressure control in patients with advanced diabetic kidney disease and heavy proteinuria. Int Urol Nephrol. 2021 Jun;53(6):1197-1207. doi: 10.1007/s11255-020-02717-2. Epub 2021 Jan 2.
- Individual participant dataSharing planned: Yes. Unique patient number in the study, biological data; no data to enable patient identification will be provided
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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.
Gabriel Mircescu, Prof study chair
Carol Davila University of Medicine and Pharmacy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Protein restriction in people with CKD Stage 4, run by Anemia Working Group Romania at 1 site in Romania.
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 7 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: status not confirmed, as of the sponsor's last update on 24 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Liliana Garneata, Assoc Prof (+40722619358, lilianagarna@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CKD progression (time frame: 15 months). 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 NCT03415074, which also lists 1 linked publication.
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 24 Feb 2020.