Clinical trial NCT01446302: Metabolic and Inflammatory Responses to Hemodialysis and the Effect of a Meal
Official title: Metabolic and Inflammatory Responses to Hemodialysis and the Effect of a Meal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Kidney Failure, Chronic
Keywords: Dialysis
Protein-energy wasting
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 1
Inflammation
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2011-10-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The objective of this study is to characterize the hormonal and inflammatory responses to hemodialysis, and to determine the effect of a meal versus fast on the metabolic changes in the post-dialytic phase.

Detailed description: Studies show that hemodialysis (HD) is a protein catabolic event per se and probably contributes to the high prevalence of protein-energy wasting among HD patients. The muscle catabolic effect of HD is probably caused by loss of amino acids (10-12 grams per dialysis session) and by exacerbation of the inflammatory and hormonal disorders already present. Activation of the immune system during HD has been linked to the contact of blood cells with the dialyzer membrane and to bacterial-derived DNA fragments in the dialysis fluid. An intradialytic increase in interleukin-6 (IL-6) has been shown to correlate with muscle protein catabolism, and because IL-6 continues to increase for 2 hours after HD has ended, there might be a considerable "carry-over effect" to the post-dialytic period. Moreover, HD induces significant changes in the insulin/insulin-like growth factor I (IGF-I) signaling pathways. Plasma insulin is cleared by HD, and the bioactivity of IGF-I is reduced by 50% during a 4-hr maintenance HD due to an up-regulation of IGF-binding protein 1 (IGFBP-1), the only acutely regulated IGFBP.

Eligibility criteria: Inclusion criteria:

* \> 18 years
* stable maintenance hemodialysis for at least 3 months
* well-functioning arteriovenous shunts with recirculation less than 5%
* informed consent

Exclusion criteria:

* diabetes mellitus
* body mass index below 18.5 or above 30.0 kg/m2
* malnutrition (global assessment score C)
* active malignant disease
* immunosuppressive treatment (including glucocorticoid treatment)
* evidence of an ongoing inflammatory disease (including infection and autoimmune disorders)
* pregnancy

Exclusion criteria during the study:

* myocardial infarction or arrythmia with hemodynamic derangements
* permanent thrombosis in the arteriovenous (AV) shunt
* severe infectious disease
* renal transplantation

Primary outcomes:
measure: Changes in serum Bioactive IGF-I and IGFBP-1 levels during and after hemodialysis
timeFrame: At 1, 2, 3, 5, 6, 7, 9, and 10 hours after start of hemodialysis
measure: Changes in plasma Interleukin-6 and serum hsCRP levels during and after hemodialysis
timeFrame: At 1, 2, 3, 5, 6, 7, 9, and 10 hours after start of hemodialysis
Secondary outcomes:
measure: Pulse wave analysis (augmentation index (AIx)) during and after hemodialysis
timeFrame: At 1, 2, 3, ,4, 5, 6, 7, 8, 9, and 10 hours after start of hemodialysis
measure: Mineral metabolism (including calcium, phosphate, PTH, and FGF-23 levels) during and after hemodialysis
timeFrame: At 1, 2, 3, 5, 6, 7, 9, and 10 hours after start of hemodialysis
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Department of Nephrology, Aarhus University Hospital, Skejby
city: Viborg
country: Denmark
facility: Department of Nephrology, Viborg Regional Hospital
Study officials:
affiliation: Department of Nephrology, Aarhus University Hospital, Skejby, Denmark
name: Per Ivarsen, MD, PhD
role: STUDY_DIRECTOR
affiliation: Department of Endocrinology and Internal Medicine & Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Denmark
name: Jan Frystyk, MD,PhD,DMSc
role: STUDY_DIRECTOR
affiliation: Department of Nephrology, Aarhus University Hospital, Skejby, Denmark
name: Bente Jespersen, MD, DMSc
role: STUDY_DIRECTOR
affiliation: Department of Endocrinology and Internal Medicine & Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Denmark
name: Jens S Christiansen, MD, DMSc
role: STUDY_DIRECTOR
affiliation: Department of Nephrology, Viborg Regional Hospital, Denmark
name: Else Randers, MD, PhD
role: STUDY_DIRECTOR
affiliation: Department of Nephrology, Aarhus University Hospital, Skejby, Denmark
name: Mark Reinhard, MD
role: PRINCIPAL_INVESTIGATOR
References: