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 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.

Mumps vaccine effectiveness in primary schools and households, the Netherlands, 2008.

To estimate the mumps vaccine effectiveness (VE) during a large genotype D mumps outbreak, we conducted a cross-sectional study in eight primary schools and associated households in the Netherlands. Questionnaires were used to collect information on the occurrence of mumps. Multivariate analyses were used to estimate VE. Among schoolchildren we estimated the VE against mumps. Among household contacts where the schoolchild was the index case we estimated the VE against mumps and against mumps infectiousness. In total 1175 children and 2281 household contacts participated in the study. The mumps attack rate among schoolchildren was 17%. The mumps VE in schoolchildren was 92% [95% confidence interval (CI) 83-96%] and 93% [85-97%] for one and two doses of the measles, mumps, rubella (MMR) vaccine, respectively. The adjusted mumps VE among household contacts was 67% [65-95%] and 11% [-4 to 88%] against mumps and mumps infectiousness, respectively. Our study indicates that the mumps component of the MMR vaccine offered adequate protection against mumps among schoolchildren. The relatively low VE among household contacts is of concern.