Clinical trial NCT05015647: Low Protein Diet in CKD Patients at Risk of Malnutrition
Official title: Is There Any Indication for Protein Free Products in Patients With Advanced CKD at Risk of Malnutrition?A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Diseases
Malnutrition
Keywords: chronic kidney disease
Malnutrition
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2021-08-20
Enrollment: 35
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants 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).
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline MIS at 6th month
timeFrame: measured at baseline and 6 months.
measure: Change from baseline serum albumin at 6th month
timeFrame: measured at baseline and at 6 months.
measure: intergroup MIS comparison at 6 months
timeFrame: 6th month
measure: Intergroup comparison of the number of patients that reached a MIS ≥8 at 6 months
timeFrame: 6th month
Secondary outcomes:
measure: Differences of GFR estimated with creatinine
timeFrame: measured at baseline and at 6 months.
measure: Differences of GFR estimated with cystatin C
timeFrame: measured at baseline and at 6 months.
measure: Differences in serum urea
timeFrame: measured at baseline and at 6 months.
measure: Differences in creatinine clarance
timeFrame: measured at baseline and at 6 months.
measure: Differences in phosphorous
timeFrame: measured at baseline and at 6 months.
measure: Differences in FGF23 intact
timeFrame: measured at baseline and at 6 months.
measure: Differences in FGF23 c-terminal
timeFrame: measured at baseline and at 6 months.
measure: Differences in urinary phosphorous
timeFrame: measured at baseline and at 6 months.
measure: Differences in PTH
timeFrame: measured at baseline and at 6 months.
measure: Differences in bicarbonate
timeFrame: measured at baseline and at 6 months.
measure: Differences in pH
timeFrame: measured at baseline and at 6 months.
measure: Differences in CRP
timeFrame: measured at baseline and at 6 months.
measure: Differences in IL6
timeFrame: measured at baseline and at 6 months.
measure: Differences in the short physical performance battery scores
timeFrame: at months 1 and 6
measure: Differences of the handgrip strength
timeFrame: measured at baseline and at 6 months.
measure: Differences in the body composition (lean body mass, fat body mass, water) in the two study groups (bio impedance)
timeFrame: measured at baseline and at 6 months.
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Unit of nephrology, dialysis and renal transplantation - Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano
Study officials:
affiliation: Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
name: Simone Vettoretti, Dr
role: PRINCIPAL_INVESTIGATOR
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