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Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial

BACKGROUND: Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and...

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Autores principales: de Boer, Nini, Guloksuz, Sinan, van Baal, Caroline, Willebrands, Leonie, Deenik, Jeroen, Vinkers, Christiaan H., Rossum, Inge Winter-van, Zinkstok, Janneke, Wilting, Ingeborg, Zantvoord, Jasper B., Backx, Frank, Swildens, Wilma E., Schouw, Marieke, Bogers, Jan, Hulshof, Folkwin, de Knijff, Rudolf, Duindam, Peter, Veereschild, Mike, Bak, Maarten, Frederix, Geert, de Haan, Lieuwe, van Os, Jim, Cahn, Wiepke, Luykx, Jurjen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783702/
https://www.ncbi.nlm.nih.gov/pubmed/33402159
http://dx.doi.org/10.1186/s12888-020-02992-4
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author de Boer, Nini
Guloksuz, Sinan
van Baal, Caroline
Willebrands, Leonie
Deenik, Jeroen
Vinkers, Christiaan H.
Rossum, Inge Winter-van
Zinkstok, Janneke
Wilting, Ingeborg
Zantvoord, Jasper B.
Backx, Frank
Swildens, Wilma E.
Schouw, Marieke
Bogers, Jan
Hulshof, Folkwin
de Knijff, Rudolf
Duindam, Peter
Veereschild, Mike
Bak, Maarten
Frederix, Geert
de Haan, Lieuwe
van Os, Jim
Cahn, Wiepke
Luykx, Jurjen J.
author_facet de Boer, Nini
Guloksuz, Sinan
van Baal, Caroline
Willebrands, Leonie
Deenik, Jeroen
Vinkers, Christiaan H.
Rossum, Inge Winter-van
Zinkstok, Janneke
Wilting, Ingeborg
Zantvoord, Jasper B.
Backx, Frank
Swildens, Wilma E.
Schouw, Marieke
Bogers, Jan
Hulshof, Folkwin
de Knijff, Rudolf
Duindam, Peter
Veereschild, Mike
Bak, Maarten
Frederix, Geert
de Haan, Lieuwe
van Os, Jim
Cahn, Wiepke
Luykx, Jurjen J.
author_sort de Boer, Nini
collection PubMed
description BACKGROUND: Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. METHODS: In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m(2)) of at least 16 years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 allocation to placebo or metformin, and will be treated for a total of 26 weeks. Metformin will be started at 500 mg b.i.d. and escalated to 1000 mg b.i.d. 2 weeks thereafter (up to a maximum of 2000 mg daily). In addition, all participants will undergo a lifestyle intervention as part of the usual treatment consisting of a combination of an exercise program and dietary consultations. The primary outcome measure is difference in body weight as a continuous trait between the two arms from treatment inception until 26 weeks of treatment, compared to baseline. Secondary outcome measures include: 1) Any element of metabolic syndrome (MetS); 2) Response, defined as ≥5% body weight loss at 26 weeks relative to treatment inception; 3) Quality of life; 4) General mental and physical health; and 5) Cost-effectiveness. Finally, we aim to assess whether genetic liability to BMI and MetS may help estimate the amount of weight reduction following initiation of metformin treatment. DISCUSSION: The pragmatic design of the current trial allows for a comparison of the efficacy and safety of metformin in combination with a lifestyle intervention in the treatment of AiWG, facilitating the development of guidelines on the interventions for this major health problem. TRIAL REGISTRATION: This trial was registered in the Netherlands Trial Register (NTR) at https://www.trialregister.nl/trial/8440 as NTR NL8840 on March 8, 2020.
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spelling pubmed-77837022021-01-05 Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial de Boer, Nini Guloksuz, Sinan van Baal, Caroline Willebrands, Leonie Deenik, Jeroen Vinkers, Christiaan H. Rossum, Inge Winter-van Zinkstok, Janneke Wilting, Ingeborg Zantvoord, Jasper B. Backx, Frank Swildens, Wilma E. Schouw, Marieke Bogers, Jan Hulshof, Folkwin de Knijff, Rudolf Duindam, Peter Veereschild, Mike Bak, Maarten Frederix, Geert de Haan, Lieuwe van Os, Jim Cahn, Wiepke Luykx, Jurjen J. BMC Psychiatry Study Protocol BACKGROUND: Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. METHODS: In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m(2)) of at least 16 years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 allocation to placebo or metformin, and will be treated for a total of 26 weeks. Metformin will be started at 500 mg b.i.d. and escalated to 1000 mg b.i.d. 2 weeks thereafter (up to a maximum of 2000 mg daily). In addition, all participants will undergo a lifestyle intervention as part of the usual treatment consisting of a combination of an exercise program and dietary consultations. The primary outcome measure is difference in body weight as a continuous trait between the two arms from treatment inception until 26 weeks of treatment, compared to baseline. Secondary outcome measures include: 1) Any element of metabolic syndrome (MetS); 2) Response, defined as ≥5% body weight loss at 26 weeks relative to treatment inception; 3) Quality of life; 4) General mental and physical health; and 5) Cost-effectiveness. Finally, we aim to assess whether genetic liability to BMI and MetS may help estimate the amount of weight reduction following initiation of metformin treatment. DISCUSSION: The pragmatic design of the current trial allows for a comparison of the efficacy and safety of metformin in combination with a lifestyle intervention in the treatment of AiWG, facilitating the development of guidelines on the interventions for this major health problem. TRIAL REGISTRATION: This trial was registered in the Netherlands Trial Register (NTR) at https://www.trialregister.nl/trial/8440 as NTR NL8840 on March 8, 2020. BioMed Central 2021-01-05 /pmc/articles/PMC7783702/ /pubmed/33402159 http://dx.doi.org/10.1186/s12888-020-02992-4 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Study Protocol
de Boer, Nini
Guloksuz, Sinan
van Baal, Caroline
Willebrands, Leonie
Deenik, Jeroen
Vinkers, Christiaan H.
Rossum, Inge Winter-van
Zinkstok, Janneke
Wilting, Ingeborg
Zantvoord, Jasper B.
Backx, Frank
Swildens, Wilma E.
Schouw, Marieke
Bogers, Jan
Hulshof, Folkwin
de Knijff, Rudolf
Duindam, Peter
Veereschild, Mike
Bak, Maarten
Frederix, Geert
de Haan, Lieuwe
van Os, Jim
Cahn, Wiepke
Luykx, Jurjen J.
Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial
title Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial
title_full Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial
title_fullStr Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial
title_full_unstemmed Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial
title_short Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial
title_sort study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the metformin-lifestyle in antipsychotic users (melia) trial
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783702/
https://www.ncbi.nlm.nih.gov/pubmed/33402159
http://dx.doi.org/10.1186/s12888-020-02992-4
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