Low Protein Diet in CKD Patients at Risk of Malnutrition

August 16, 2021 updated by: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Is There Any Indication for Protein Free Products in Patients With Advanced CKD at Risk of Malnutrition?A Pilot Randomized Controlled Trial

It's a pilot study with an open label randomized-controlled design. Estimated number of patients should have been 38, taking in account of a maximal drop out up to 20% of the sample. We enrolled 35 patients, 27 of whom terminated the study as per protocol (14 in the Low protein (LP) group and 13 in the Normo Protein (NP) group).

Patients were treated for six months with two different dietary prescriptions:

  1. LP group (n=17) was prescribed high calories/low proteins diet (30 Kcal/kg and 0.6-0.7gr/kg respectively). In order to assure prescribed calorie intake, this group was supplemented with commercial protein free products (protein content <2%).
  2. NP group (n=18) was prescribed high calories/normal proteins diet (30 kcal/kg and 0.8 gr/kg respectively).

The primary hypothesis of the study was that in CKD patients at risk of malnutrition (4 ≤ MIS ≥7) with a persistent spontaneous low protein and calories intake, the prescription of a LP diet was not inferior to NP diet regarding the development of malnutrition (i.e.MIS ≥ 8).

We also wanted to test whether in these patients, the prescription of a LP diet was superior to the NP comparator regarding the control of the metabolic complication of chronic kidney diseases (i.e hyperphosphatemia, inflammation and metabolic acidosis), the progression on dyna/sarcopenia, inflammation and possibly on the progression of renal disease itself.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Nutritional status will be evaluated through:

  • Malnutrition Inflammation Score (MIS),
  • Anthropometric measurements,
  • albumin, prealbumin, transferrin,
  • 24h urinary nitrogen,
  • bioimpedance analysis (BIA),
  • periodic 24h dietary diaries,
  • International Society of Renal Nutrition and Metabolism (ISRNM),

Physical performance will be evaluated through:

  • Short Physical Performance Battery (SPPB)
  • Handgrip strength

Inflammation assessment:

  • c-reactive protein (CRP)
  • Interleukine-6 (IL6)
  • whole blood Neutrophil/lymphocyte ratio

Renal function assessment:

  • eGFR based on serum creatinine and cystatin C
  • average creatinine and urea clearance

Uremic metabolic alteration:

  • serum urea
  • serum phosphate
  • serum FGF23
  • parathormone (PTH),
  • plasma pH and bicarbonate

Time points of evaluation Dietary compliance has been assessed by a trained nutritionist at months 1, 2, 3 and 6. Dietary consumption was estimated by using dietary diaries and normalized catabolic protein rate (nPCR) measurement at baseline, 3 and at 6 months.

Nutritional status and physical performance have been evaluated monthly for the first three months and then at 6 months.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20122
        • Unit of nephrology, dialysis and renal transplantation - Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • advanced CKD not yet on renal replacement therapy (10< - eGFRcreat <30 ml/min)
  • age >65 years
  • at risk of malnutrition at Malnutrition Inflammation Score (4≤MIS≤7)
  • spontaneous low protein-energy intake (proteins < 0.8g/kg and energy < 25 kcal/kg).

Exclusion Criteria:

  • Active chronic infectious diseases
  • Heart failure of severity > NYHA2
  • Active neoplastic diseases
  • Inability to cooperate
  • Presumed overall life expectancy < 6 month
  • Decompensated liver diseases
  • Malabsorption
  • Decompensated thyroid o surrenal diseases
  • Refusal to participate
  • Immunosuppressive and/or steroid therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LP group
LP group (n=17) was prescribed high calories/low proteins diet (30 Kcal/kg and 0.6-0.7gr/kg respectively) supplemented with commercial protein free products (protein content <2%).
Dietary supplement: LP group
LP group patients replaced pasta, bread, biscuits etc. with low protein substitutes. We allowed them to consume more animal products than NP, preferring white meat to red meat and trying to limit cold cuts as much as possible. Furthermore, they were advised to prefer fresh or frozen fish, instead of dried or smoked one as well as to prefer fresh cheeses to seasoned ones. As for legumes, we advised to combine them with bread or normal cereals, for protein complementarity.
Active Comparator: NP group
NP group (n=18) was prescribed high calories/normal proteins diet (30 kcal/kg and 0.8 gr/kg respectively)
Other: NP group
NP group was given the indication to try to eat the second dish only once a day or to split the portion of the second plate between lunch and dinner, if they wanted to keep the habit of making the meal complete. It was also given the indication to prefer, among protein sources, those of plant origin. We also indicated to alternate or replace cow's milk with plant substitutes such as: rice, almonds' or oats' drinks. Furthermore, we suggested to prefer white meat and to avoid offal and processed meat. Moreover, we indicated to substitute dried or smoked fish with fresh or frozen one.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline MIS at 6th month
Time Frame: measured at baseline and 6 months.
Malnutrition-inflammation score is a validated scoring system for the assessment of malnutrition and inflammation syndrome in patients with CKD. MIS involves the evaluation of ten different domains, each of which is categorized with 4 severity levels (score scale 0-3). A total score of 4-7 was considered indicative of mild malnutrition and a score ≥8 of severe malnourishment
measured at baseline and 6 months.
Change from baseline serum albumin at 6th month
Time Frame: measured at baseline and at 6 months.
in g/dL
measured at baseline and at 6 months.
intergroup MIS comparison at 6 months
Time Frame: 6th month
Malnutrition-inflammation score is a validated scoring system for the assessment of malnutrition and inflammation syndrome in patients with CKD. MIS involves the evaluation of ten different domains, each of which is categorized with 4 severity levels (score scale 0-3). A total score of 4-7 was considered indicative of mild malnutrition and a score ≥8 of severe malnourishment
6th month
Intergroup comparison of the number of patients that reached a MIS ≥8 at 6 months
Time Frame: 6th month
Malnutrition-inflammation score is a validated scoring system for the assessment of malnutrition and inflammation syndrome in patients with CKD. MIS involves the evaluation of ten different domains, each of which is categorized with 4 severity levels (score scale 0-3). A total score of 4-7 was considered indicative of mild malnutrition and a score ≥8 of severe malnourishment
6th month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differences of GFR estimated with creatinine
Time Frame: measured at baseline and at 6 months.
In ml/min/1,73m^2
measured at baseline and at 6 months.
Differences of GFR estimated with cystatin C
Time Frame: measured at baseline and at 6 months.
in ml/min/1,73m^2
measured at baseline and at 6 months.
Differences in serum urea
Time Frame: measured at baseline and at 6 months.
in mg/dl
measured at baseline and at 6 months.
Differences in creatinine clarance
Time Frame: measured at baseline and at 6 months.
in ml/min
measured at baseline and at 6 months.
Differences in phosphorous
Time Frame: measured at baseline and at 6 months.
in mg/dl
measured at baseline and at 6 months.
Differences in FGF23 intact
Time Frame: measured at baseline and at 6 months.
in pg/mL
measured at baseline and at 6 months.
Differences in FGF23 c-terminal
Time Frame: measured at baseline and at 6 months.
in RU/mL
measured at baseline and at 6 months.
Differences in urinary phosphorous
Time Frame: measured at baseline and at 6 months.
in mg/24h
measured at baseline and at 6 months.
Differences in PTH
Time Frame: measured at baseline and at 6 months.
in ng/L
measured at baseline and at 6 months.
Differences in bicarbonate
Time Frame: measured at baseline and at 6 months.
in mEq/L
measured at baseline and at 6 months.
Differences in pH
Time Frame: measured at baseline and at 6 months.
pH
measured at baseline and at 6 months.
Differences in CRP
Time Frame: measured at baseline and at 6 months.
in mg/dl
measured at baseline and at 6 months.
Differences in IL6
Time Frame: measured at baseline and at 6 months.
in pg/mL
measured at baseline and at 6 months.
Differences in the short physical performance battery scores
Time Frame: at months 1 and 6
SPPB includes: test of standing balance, 4-meter walk and time to rise from a chair five times. Each SPPB component test is scored from 0 to 4. Higher scores indicate better physical performance
at months 1 and 6
Differences of the handgrip strength
Time Frame: measured at baseline and at 6 months.
in Kg. Handgrip strength was measured with Jamar dynamometer and was considered to be impaired for values <16kg in females and <27kg in males
measured at baseline and at 6 months.
Differences in the body composition (lean body mass, fat body mass, water) in the two study groups (bio impedance)
Time Frame: measured at baseline and at 6 months.
water in L, Lean body mass in Kg/m2 and fat body mass in Kg/m2. Body composition was measured by using a multifrequency bioelectrical impedance analysis device (BCM- Body Composition Monitor, Fresenius Medical Care, Bad Homburg, Germany).
measured at baseline and at 6 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Investigators

  • Principal Investigator: Simone Vettoretti, Dr, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2018

Primary Completion (Actual)

June 12, 2020

Study Completion (Actual)

June 12, 2020

Study Registration Dates

First Submitted

August 11, 2021

First Submitted That Met QC Criteria

August 16, 2021

First Posted (Actual)

August 20, 2021

Study Record Updates

Last Update Posted (Actual)

August 20, 2021

Last Update Submitted That Met QC Criteria

August 16, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1274/2018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

since it is a collaborative study, the data may be made available to other researchers only following a specific and motivated request that must be approved by all members of the consortium

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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