Early Administration of L-carnitine in Hemodialysis Patients

Early Administration of L-carnitine in Hemodialysis Patients: Double Blind Randomized Trial Versus Placebo

Hemodialysis is a cause of carnitine deficiency. The deficiency of carnitine induces an anemia by an increase fragility of the red blood cells, a muscular fatigue and a cardiac dysfunction. We proposed to evaluate the benefit of an early administration of L-carnitine in hemodialysis patients. The patients should be included in the first month after the start of chronic hemodialysis, randomized to receive L-carnitine or placebo and should be followed-up during one year.

Study Overview

• Status: Completed
• Conditions: Complication of Hemodialysis; Hyperthyroidism Treated or Under Control
• Intervention / Treatment: Drug: L-Carnitine

Detailed Description

The first aim of the study is to compare the resistance index to erythropoietin (hemoglobin level / rHuerythropoietin dose) with L-carnitine versus placebo Double blind randomized study evaluating the supplementation with L-carnitine versus placebo in patients beginning chronic hemodialysis for less than 1 month.

Primary outcome to compare rHuerythropoietin resistance index defined as hemoglobin level / rHuEPO dose ratio with L-carnitine and with placebo.

Secondary endpoints to compare acylcarnitine / carnitine ratio, number of red blood cells transfusion, physical status, quality of life, hypotensive episodes, lipid profile, diabetes profile, albuminemia, c reactive protein.

Several variables that influenced primary and secondary endpoints will be included in a multivariate analysis; albuminemia, c reactive protein, iron status, dialysis efficiency, protein intake, lipid intake, treatment with additional vitamins (C, B9, B6), treatment with statins, treatment of predialysis hypotension by midodrine, antihypertensive treatments.

Statistical analysis:

• description of the cohort
• comparisons of each evaluated variables between the 2 treatments
• ANOVA study for repeated measurements from inclusion to month-12 for Hb / rHuEPO dose to compare the course of the ratio between each group in intention to treat analysis
• analysis of the ratio Hb / rHuEPO month by month and taking into account tempera withdrawal

Following analysis in both intention to treat and per protocol analysis:

• acylcarnitine / carnitine ratio by ANOVA for repeated data
• number of predialysis hypotension by Chi2 test
• number of red blood cells transfusion by Chi2 test
• SF-36 physical status by comparison of mean
• SF-36 total score by comparison of mean
• lipid profile by ANOVA for repeated data
• HbA1c by ANOVA for repeated data
• variables that influenced primary and secondary variables will be analyzed by multivariate analysis
• statistical study of clinical events per month

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75004
    • Assistance Publique Hopitaux de Paris
  • Paris, France, 75013
    • HOPITAL LA PITIE SALPETRIERE, service de Néphrologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with less than 1 month on hemodialysis.
• Treated with rHuEPO.
• Male or female aged of more than 18 years old.
• With contraception treatment for women of procreation age.
• Having received and understand information.

Exclusion Criteria:

• Patients with no need of rHuEPO
• Patients with cancer disease
• Patients with life expectancy under 6 months
• Patients having a proved carnitine deficiency before the start of hemodialysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: DOUBLE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; L-Carnitine	Drug: L-Carnitine; L-Carnitine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resistance index to erythropoietin	Resistance index to erythropoietin	during de study
Haemoglobin level/weekly rHuerythropoietin dose in patients receiving l-carnitine versus those receiving the placebo.	Haemoglobin level/weekly rHuerythropoietin dose in patients receiving l-carnitine versus those receiving the placebo.	during the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acylcarnitine/carnitine ratio measured quarterly	Acylcarnitine/carnitine ratio measured quarterly	during the study
Number of red blood cells transfusion per patient during the study, data collected monthly	Number of red blood cells transfusion per patient during the study, data collected monthly	during the study
Predialysis hypotension per patient during the study, data collected monthly	Predialysis hypotension per patient during the study, data collected monthly	during the study
SF 36 physical and total score at inclusion and at the end of the study	SF 36 physical and total score at inclusion and at the end of the study	during the study
Lipid profile, measured quarterly	Lipid profile, measured quarterly	during the study
HbA1c, measured quarterly for diabetic patients and patients with glucose intolerance	HbA1c, measured quarterly for diabetic patients and patients with glucose intolerance	during the study
Albuminemia measured quarterly	Albuminemia measured quarterly	during the study
c reactive protein measured quarterly	c reactive protein measured quarterly	during the study

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Lucile Mercadal, MD,PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Mercadal L, Tezenas du Montcel S, Chonchol MB, Debure A, Depreneuf H, Servais A, Bassilios N, Assogba U, Allouache M, Prie D. Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial. Am J Nephrol. 2018;48(5):349-356. doi: 10.1159/000494338. Epub 2018 Nov 8.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (ACTUAL): June 1, 2010
• Study Completion (ACTUAL): June 1, 2010

Study Registration Dates

• First Submitted: May 3, 2006
• First Submitted That Met QC Criteria: May 3, 2006
• First Posted (ESTIMATE): May 5, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): May 4, 2011
• Last Update Submitted That Met QC Criteria: May 3, 2011
• Last Verified: March 1, 2007

More Information

Terms related to this study

• Keywords: Hemodialysis; Anaemia; L-carnitine supplementation; Erythropoietin responsiveness
• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hyperthyroidism
• Other Study ID Numbers: P050316