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Open Access 01-12-2021 | Schizophrenia | Study protocol

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

Authors: Nini de Boer, Sinan Guloksuz, Caroline van Baal, Leonie Willebrands, Jeroen Deenik, Christiaan H. Vinkers, Inge Winter-van Rossum, Janneke Zinkstok, Ingeborg Wilting, Jasper B. Zantvoord, Frank Backx, Wilma E. Swildens, Marieke Schouw, Jan Bogers, Folkwin Hulshof, Rudolf de Knijff, Peter Duindam, Mike Veereschild, Maarten Bak, Geert Frederix, Lieuwe de Haan, Jim van Os, Wiepke Cahn, Jurjen J. Luykx

Published in: BMC Psychiatry | Issue 1/2021

Abstract

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/m²) 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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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
Authors: Nini de Boer
Sinan Guloksuz
Caroline van Baal
Leonie Willebrands
Jeroen Deenik
Christiaan H. Vinkers
Inge Winter-van Rossum
Janneke Zinkstok
Ingeborg Wilting
Jasper B. Zantvoord
Frank Backx
Wilma E. Swildens
Marieke Schouw
Jan Bogers
Folkwin Hulshof
Rudolf de Knijff
Peter Duindam
Mike Veereschild
Maarten Bak
Geert Frederix
Lieuwe de Haan
Jim van Os
Wiepke Cahn
Jurjen J. Luykx
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Schizophrenia
Antipsychotics
Metformin
Antipsychotics
Clozapine
Published in: BMC Psychiatry / Issue 1/2021
Electronic ISSN: 1471-244X
DOI: https://doi.org/10.1186/s12888-020-02992-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

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