Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)

Introduction Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). R...

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Main Authors: Lotte Haverman, Ron A A Mathôt, Floor Veltkamp, Djera H Khan, Christa Reefman, Susan Veissi, Hedy A van Oers, Elena Levtchenko, Sandrine Florquin, Joanna A E van Wijk, Michiel F Schreuder, Antonia H M Bouts
Format: Article
Language:English
Published: BMJ Publishing Group 2019-09-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/8/e027011.full
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author Lotte Haverman
Ron A A Mathôt
Floor Veltkamp
Djera H Khan
Christa Reefman
Susan Veissi
Hedy A van Oers
Elena Levtchenko
Sandrine Florquin
Joanna A E van Wijk
Michiel F Schreuder
Antonia H M Bouts
author_facet Lotte Haverman
Ron A A Mathôt
Floor Veltkamp
Djera H Khan
Christa Reefman
Susan Veissi
Hedy A van Oers
Elena Levtchenko
Sandrine Florquin
Joanna A E van Wijk
Michiel F Schreuder
Antonia H M Bouts
author_sort Lotte Haverman
collection DOAJ
description Introduction Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome).Methods and analysis An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2–16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores.Ethics and dissemination The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal.Trial registration number NL6826, 2017-001025-41
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spelling doaj-art-0050583e9b7849988fe7852140461b342025-08-20T02:11:41ZengBMJ Publishing GroupBMJ Open2044-60552019-09-019810.1136/bmjopen-2018-027011Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)Lotte Haverman0Ron A A Mathôt1Floor Veltkamp2Djera H Khan3Christa Reefman4Susan Veissi5Hedy A van Oers6Elena Levtchenko7Sandrine Florquin8Joanna A E van Wijk9Michiel F Schreuder10Antonia H M Bouts11Child and Adolescent Psychiatry and Psychological Care, Emma Children’s Hospital, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsHospital Pharmacy - Clinical Pharmacology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands1 Paediatric Nephrology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands2 Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands1 Paediatric Nephrology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands3 Paediatric Nephrology, Radboudumc, Nijmegen, The Netherlands4 Psychosocial Department, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands5 Paediatric Nephrology, Universitaire Ziekenhuizen Leuven, Leuven, Belgium2 Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands7 Paediatric Nephrology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands3 Paediatric Nephrology, Radboudumc, Nijmegen, The NetherlandsDepartment of Pediatric Nephrology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsIntroduction Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome).Methods and analysis An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2–16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores.Ethics and dissemination The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal.Trial registration number NL6826, 2017-001025-41https://bmjopen.bmj.com/content/9/8/e027011.full
spellingShingle Lotte Haverman
Ron A A Mathôt
Floor Veltkamp
Djera H Khan
Christa Reefman
Susan Veissi
Hedy A van Oers
Elena Levtchenko
Sandrine Florquin
Joanna A E van Wijk
Michiel F Schreuder
Antonia H M Bouts
Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)
BMJ Open
title Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)
title_full Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)
title_fullStr Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)
title_full_unstemmed Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)
title_short Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)
title_sort prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome study protocol for a double blind randomised placebo controlled trial the learns study
url https://bmjopen.bmj.com/content/9/8/e027011.full
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