Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03818568 |
| Other study ID # |
2015-785-038 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2017 |
| Est. completion date |
February 1, 2021 |
Study information
| Verified date |
August 2021 |
| Source |
Coordinación de Investigación en Salud, Mexico |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Investigators intend to analyze diets restricted in protein and supplemented with
ketoanalogues of essential amino acids, to slow the progress of renal damage and improve
nutritional status in diabetic patients over 60 years with stage 4 chronic kidney disease.
Evey 2 months, evaluations were performed of renal function (creatinine clearance, serum
cysteine, proteinuria) and nutritional status (subjective global evaluation,dominant had
pressure strength, body composition by bioelectric impedance, serum transferrin, serum
prealbumin and serum aminogram) for a follow-up period of 2 years.
Description:
Design. A multicenter, controlled, randomized, open label clinical trial was performed in
patients with T2DM in CKD stage 3b-4 (GFR <44 to >15 mL/min/1.73 m2) treated in hospitals of
the Mexican Social Security Institute. The follow-up period was at least 1 year from the
inclusion of the last patient. The study was conducted in accordance with the provisions of
the Declarations of Helsinki and Tokyo with the amendments in Venice (1983). The protocol was
approved by the National Research and Ethics Committee and by the Research Committees of all
participating hospitals and was registered in National Clinical Trials (NCT03818568).
Patients. Inclusion criteria: Adult patients with T2DM (>18 years) of either sex, with stage
3b-4 of CKD. All patients gave their signed informed consent at the time of recruitment.
Exclusion criteria: Previous treatment with KA, kidney transplantation, cancer, HIV-AIDS, or
seropositive for hepatitis B or C, patients receiving immunosuppressors, with hypercalcemia,
intolerance to KA or disorders of amino acid metabolism. Patients who lost social security
during the study, changed address or treating physician were also excluded.
Sample size. Sample size calculation was made on the basis of two independent groups with
unequal variances, α=0.05, β=0.20, and assuming a difference of 4.0 mL/min/yr between groups
in reduction of eGFR, lower in LPD+KA. Calculation was made with sample size software. A
minimum of 51 per group was obtained.
Intervention. Diet design. Energy: 35 kcals/kg of ideal body weight in patients with normal
BMI; 30 kcals/kg of ideal body weight in overweight patients (BMI>25 kg/m2) and 40 kcals/kg
of ideal weight in underweight patients (BMI<25 kg/m2). Lipids accounted for 35% of the total
energy intake (2/3 from polyunsaturated fatty acids). Carbohydrate intake was set at 55-60%
of the total energy intake, with >70% of complex carbohydrates. The fiber content was 20-25 g
per day. The dietary recommendation for sodium chloride was ~5 g daily and potassium 50-60
mEq/day. Phosphate intake was set at 800-1000 mg per day.
Both groups were prescribed with PrI of 0.6 g/kg/day, preferably plant-based. Patients in
LPD+KA group received KA (Ketosteril® (Fresenius Kabi, Deutschland GMBH, BadHomburg, Germany)
according to the manufacturer's recommendations (1 tablet/5 kg of body weight divided into 3
doses). All other treatments were provided according to institutional guidelines and
prescribed by and according to the criteria of the treating physicians.
Randomization. Patients were centrally randomized 1:1 using an electronic system of random
numbers generator.
Outcomes. The primary outcome was: the rate of decline in kidney function (Δ eGFR/year).
Secondary outcomes included: start of dialysis, impairment of nutritional status, adverse
events, hospitalizations, and mortality.
Follow-up. Patients were followed-up with scheduled visits every two months, for clinical and
biochemical evaluation. Blood samples were obtained after an overnight fast, serum and plasma
were separated and kept in frozen aliquots (-70 °C) until assay. The 24 h urine volumes were
recorded and frozen aliquots stored (-70 °C) until assay. In total blood, hemoglobin,
hematocrit, and glycated hemoglobin were measured, and in plasma/serum: glucose, urea,
creatinine, albumin, total proteins, triglycerides, total cholesterol, HDL cholesterol,
calcium, phosphorus, C-reactive protein. In 24-hour urine: urea and creatinine. Serum
Cystatin-C was measured at baseline and months 6, 9 and 12.
Measurements of biochemical parameters were performed on automated equipment using routine
techniques. High sensitivity C-reactive protein and Cystatin-C were measured by
immunoturbidimetry (Diazyme's Cystatin C Assay. Poway, CA, USA). The protein nitrogen
appearance normalized by body weight (nPNA) was calculated with the Maroni formula, GFR was
calculated using formulas based on sCr (eCKDCr), and serum Cystatin C (eGFRCysC).
Nutritional evaluations. The patients were evaluated by Nephrology Nutritionists. Nutritional
status was monitored by body weight, body mass index, subjective global assessment, body
composition analyzed by electrical bioimpedance, and biochemical parameters. As a functional
index, the hand grip force was measured with a dynamometer. Treatment adherence was monitored
by the 24-hour food intake questionnaire and/or the 3-day food intake diary, nPNA was also
used. In the intervention group, adherence to the use of KA was evaluated by counting tablets
and packaging at each visit.
Statistical analysis. Data are presented as means and standard deviations or standard errors
and as percentages or frequencies according variable characteristics. Differences between
groups were analyzed with Chi2 test, or Student´s t test. For calculation of decline of GFR
during follow-up, only actual eGFR data were considered, and two-way analyses of variance
used. For analysis of the effect of concomitant medication, differences in slopes of
regression lines of eGFR over time among users and non-users of specific medication were
used. Differences in distribution of adverse events was analyzed with Chi2 and
Kolmogorov-Smirnov test. All statistical calculations were made with wSPSS v19 package.
