LPD+α-ketoacids on Autophagy and Improving Muscle Wasting in CKD

Phase 4

• Conditions: Muscular Atrophy
• Interventions: Drug: keto-amino acids

• Registration Number: NCT02568020
• Lead Sponsor: YUAN Wei-jie

Brief Summary

To investigate the effects of different dietary regimens on muscle wasting, insulin/IGF-1 resistance. Further, to explore whether LPD+KA decrease the activation of autophagy associate with insulin/IGF-1 pathway.

Detailed Description

1. Dietary assessment: The composition of the diet will be evaluated through questionnaire, and analyzed a computer-based nutritional evaluation with Dieta software.

2. Biochemical data: blood samples will be collected at baseline and every 3 months of routine examination, such as blood routine, biochemistry, HbA1c, Serum IGF-1, CRP, will be measured. Homeostatic model assessment score (HOMA-IR) was recorded.

3. Skeletal muscle assessment: the parameters of skeletal muscle will be assessed before and after dietary intervention for 12 months. Body weight, height, Body mass index, skeletal muscle mass will be measured by Body composition analyzer. Quadriceps strength will be assessed with a seated leg press exercise instrument (Keiser Sport, Fresno, CA, USA) using the five repetition maximum technique. Knee and hip extension power (rate of generating force) will be assessed with a validated leg power instrument (University ofNottingham Medical College, Nottingham, UK). Fatigability will be assessed with the same bilateral leg press exercise used in strength testing.

Study Timeline

• Study First Submitted: 2015-09-30
• Study First Submitted QC: 2015-09-30
• Study First Posted: 2015-10-05
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-31
• Study Start: 2016-11
• Last Update Posted: 2016-11-01
• Primary Completion: 2018-12
• Study Completion: 2019-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• patients agree to participate in this study; age≥18 years and<70years; renal function measured with creatinine clearance<60 and >15 ml/min (three monthly consecutive measurements)；at least 6 months of follow up at our clinic before recruitment and haven't received any diet intervention.

Exclusion Criteria

• pregnant patients; diabetes; heart or liver failure; a recent myocardial infarction (in the last 12 months); long term immobilization; chronic respiratory failure; cancer; any pharmacological treatment that could modify muscle structure or function such as glucocorticoids or insulin；Contraindications of Ketosteril, such as hypersensitivity to the active substances or to any of the excipients, hypercalcaemia, disturbed amino acid metabolism to the study protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LPD+KA	keto-amino acids	LPD+KA group will be supplemented with keto-amino acids (Ketosteril®, Fresenius Kabi) at a dosage of one tablet/5kg ideal body weight/day, divided into three doses taken during meals.The patients will be followed-up for one year. The patients will come to the hospital every 4 weeks.

Primary Outcome Measures

Name	Time	Method
Quadriceps strength assessment	1 year	the parameters of skeletal muscle will be assessed before and after dietary intervention for 12 months. Quadriceps strength will be assessed with a seated leg press exercise instrument (Keiser Sport, Fresno, CA, USA) using the five repetition maximum technique.
Body weight assessment	1 year	the parameters of skeletal muscle will be assessed before and after dietary intervention for 12 months. Body weight will be measured to calculate Body mass index.
Knee and hip extension power assessment	1 year	the parameters of skeletal muscle will be assessed before and after dietary intervention for 12 months. Knee and hip extension power (rate of generating force) will be assessed with a validated leg power instrument (University ofNottingham Medical College, Nottingham, UK).
Fatigability assessment	1 year	the parameters of skeletal muscle will be assessed before and after dietary intervention for 12 months. Fatigability will be assessed with the same leg power instrument (University ofNottingham Medical College, Nottingham, UK) as used in strength testing.
Height assessment	1 year	the parameters of skeletal muscle will be assessed before and after dietary intervention for 12 months. Height will be measured to calculate Body mass index
skeletal muscle mass	1 year	the parameters of skeletal muscle will be assessed before and after dietary intervention for 12 months. muscle circumference including mid-arm, mid-thigh, and mid-calf circumferences will be assessed.

Secondary Outcome Measures

Name	Time	Method
computer-based nutritional assessment	1 year	analyzed a computer-based nutritional evaluation with Dieta software.
Dietary assessment	1 year	The composition of the diet will be evaluated through questionnaire
calculate HOMA-IR	1 year	Homeostatic model assessment score (HOMA-IR) was recorded.
Biochemical data	1 year	blood samples will be collected at baseline and every 3 months of routine examination, such as blood routine, biochemistry, HbA1c, Serum IGF-1, CRP, will be measured.
Safety parameters	1 year	Blood routine：including WBC, RBC, Hb, PLT, HCT; Blood biochemistry：including Ca, P, iPTH, albumin, prealbumin, transferrin, creatinine, Bun，CRP Blood fat: cholesterol, triglyceride（VLDL、LDL、HDL）