Monitoring of Metabolic Adverse Events of Second Generation Antipsychotics in a Naive Pediatric Population Followed in Mental Health Outpatient and Inpatient Clinical Settings (MEMAS Prospective Study)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Participant's demographic informations
研究概览
简要总结
Introduction: Second Generation Antipsychotics (SGAs) are widely used in the pediatric population. It is currently established that SGAs may induce undesirable metabolic adverse events (AEs) such as weight gain, metabolic changes in blood lipids or glucose with risk of potential cardiovascular morbidity and mortality. The Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in children (CAMESA) has published recommendations for monitoring the metabolic AEs of SGAs in the pediatric population. Factors that may be associated with the onset of SGA's metabolic AEs and long term consequences are less studied in the literature. The objectives of our research are to evaluate some factors that can influence the development of the SGA's metabolic AEs, and to study clinical adherence to CAMESA guidelines.
Methods and analysis: The MEMAS study (Monitoring des Effets Métaboliques des Antipsychotiques de Seconde Génération) design is a multicenter, prospective, longitudinal observational study with repeated measures of metabolic monitoring up to 24 months of follow-up. Two recruiting centers have been selected for patients under 18 years of age, previously naïve of antipsychotics, starting an SGA or who have started an SGA for less than 4 weeks regardless of the diagnosis that motivated the prescription. Assessments are performed at inclusion and during follow-up for anthropometric measures (AM), blood pressure (BP) and blood tests (BT) at baseline and 1, 2, 3, 6, 9, 12 and 24 months of follow-up.
Ethics and dissemination: The study protocol was approved by the Centre Hospitalier Universitaire (CHU) Sainte-Justine's Research Ethics Board (MP-21-2016-1201) in 2016 and obtained institutional suitability for the "Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Île-de-Montréal" (CIUSSS NIM) Research Center in May 2018. For all participants, written consent will be obtained from parents/caregivers as well as the participant's assent in order to enable their participation in this research project. The results of this research will be published.
详细描述
Objectives The primary objective is to study selected factors that can influence the development of the SGA's metabolic AEs such as the main diagnosis for which the SGA is prescribed, comorbidities, type and dose of AP, metabolic family history (siblings, parents, parents' siblings, grandparents) and the patient's characteristics (age, height, ethnicity, weight, puberty status). We hypothesize that factors such as younger age of exposure, SGA type, higher SGA doses, lower BMI, non-white ethnic status, hospitalization status at baseline and longer treatment duration will be associated with greater weight gain and, potentially, more cardio-metabolic complications. The secondary objective is to evaluate the clinical adherence to CAMESA guidelines for monitoring of SGAs metabolic AEs in current practice. We hypothesize that the monitoring rates will be low.
Trial design The MEMAS study design is a multicenter, prospective, longitudinal observational study with repeated measures of metabolic monitoring up to 24 months of follow-up. Two recruiting centers have been selected. Recruitment started in January 2017 at CHU Sainte-Justine Hospital and in May 2018 at CIUSSS NIM including the Rivière-des-Prairies (HSM RDP) and Albert-Prévost Mental Health Hospitals (HSM AP). Patients have been included for up to 4 weeks after the initiation of SGA treatment (baseline). Patients will be assured a safe follow-up on their pharmacotherapy. Adherence to the proposed follow-up calendar by the CAMESA guidelines will allow for the detection and the early management of potential cardiometabolic AEs of SGAs. Assessments are performed at inclusion and during follow-up for anthropometric measures (AM), blood pressure (BP) and blood tests (BT) at baseline and 1, 2, 3, 6, 9, 12 and 24 months of follow-up. Participation in this study does not lead to any additional risk to current medical practices. Study participation will end when the patient reaches the end of their 24-month follow-up or earlier if the SGA treatment is discontinued. The prescription of SGA (including dose adjustments, end of treatment, switches and comedications) by the treating psychiatrist is clinically naturalistic. However, during this study, if measured parameters reach what is considered a critical value, the psychiatrist will be notified by the nurse or a member of the research team so that the patient can be referred to a specialist in order to have the proper intervention recommended by the CAMESA guidelines (Ho et al., 2011; Raffin et al., 2014).
Measures All anticipated measurements during the follow-up are : Demographic and clinical baseline data, Adherence to treatment, Anthropometric measures (AM), Blood pressure, Blood tests, and The "MEMAS questionnaire on lifestyle habits and stages of puberty".
Blood tests are performed on site for patients included at HSM AP or Sainte-Justine Hospital whenever possible. For patients included at HSM RDP, blood samples are performed in a local community service center (CLSC) or elsewhere, depending on available resources.
Data collection process In each recruitment center, nurses monitor the participant's studied variables according to the CAMESA calendar. Data is collected and coded from participant's medical records by a member of the research team. All data is anonymized and preserved in the participant's research file. All of the collected information will be kept confidential unless authorized by the participant or his caregiver or an exception from the law. The computerized data will be kept on a password protected file and the paper questionnaires will be kept in a locked space. The data collected will be kept for seven years after the end of the study. After this period of time, it will be safely deleted or destroyed by shredding. The parameters collected for the metabolic monitoring of each SGA-treated participant during follow-up were based on the recommendations of CAMESA guidelines as well as on other, more recent, clinical landmark studies (Nielsen et al., 2014; Pringsheim et al., 2011; Raffin et al., 2014; Rubin et al., 2015). This clinical research project does not require any further investigation compared to the standards of best practice.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients under 18 years of age,
- •previously AP-naifs,
- •starting an SGA or who started an SGA for less than 4 weeks,
- •followed longitudinally at one of the selected recruiting center,
- •regardless of the diagnosis that motivated the prescription of the SGA medication.
排除标准
- •diabetes,
- •dyslipidemia,
- •high blood pressure,
- •thyroid dysfunction,
- •hepatic disease,
- •hyperprolactinemia,
- •taking a medication to treat any of the above conditions before starting SGA treatment and pregnancy.
结局指标
主要结局
Participant's demographic informations
时间窗: At baseline (inclusion)
Sex, age, ethnic group, socioeconomic status will be collected
Evaluation of Adherence to second generation antipsychotic treatment
时间窗: At 24 months of follow-up
Compliance will be indirectly estimated by the nurse and/or the treating psychiatrist at each measurement time of the CAMESA calendar, according to a voluntary declaration by the participants. The date of renewal of the psychotropic medication will also be verified using the Quebec medical record database ("Dossier Santé Québec (DSQ)") and compared to the patient's declaration. The adherence will therefore be counted as the number of days of missed SGA dose per week or per month.
Assessment of change of Blood pressure at different times of the study
时间窗: At baseline, at 1, 2, 3, 6, 9, 12 and 24 months of follow-up
Systolic and diastolic pressures will be assessed and considered abnormal when it is equal to or higher than the 90th percentile to follow pediatric standards (Cook et al. 2003; Weiss et al., 2004).
Assessment of change of thyroid stimulating hormone (TSH) level at different times of the study
时间窗: At baseline, at 6, 12 and 24 months of follow-up.
Laboratory testing includes thyroid stimulating hormone level with normal rate \< 10 milliunits per liter (mU/L).
Assessment of change in responses to the eating habits MEMAS questionnaire at different times of the study
时间窗: At baseline, at 1, 3, 6, 12 and 24 months of follow-up
Eating habits will be assessed using a Food Frequency Questionnaire from the Canadian branch of the Health Behavior in School-aged Children study (Currie et al., 2010; Vereecken \& Maes, 2003) and culturally adapted by the ISCOLE team. These items are rated from 1 (no day a week) to 6 (5 days a week). Additional items concerning snacks while watching television (Van den Bulck \& Van Mierlo, 2004), school meals (Johnson et al., 2014), meals from outside. These items are rated from 1 (no day a week) to 6 (5 days a week). Emotional hunger (Striegel-Moore et al., 1999) are also included. These items are rated from 1 (" never or almost never ") to 3 (" usually or always ").
Assessment of change of Tanner scores at different times of the study
时间窗: At baseline, at 1, 3, 6, 12 and 24 months of follow-up
Puberty status will be assessed using a questionnaire developed by Morris and Udry (1980) which includes illustrations of the five Tanner stages of pubertal development, accompanied by brief descriptions (stage 1 = no puberty, stade 2 = completed puberty).
Assessment of change of Body Mass Index (BMI) at different times of the study
时间窗: At baseline, at 1, 2, 3, 6, 9, 12 and 24 months of follow-up
Assessment of weight and height will be taken using the same instruments and according to a standardized technique. Body Mass Index (BMI) will be calculated with the weight (kilograms) divided by the height squared (m2). Then, the BMI is standardized for sex and age according to the growth charts of the Centers for Disease Control (CDC) (Ogden et al., 2002) in order to obtain the BMI-z score. Significant weight gain is defined by a 0.5 increase in BMI-z score. Being overweight is defined by a BMI-z between the 85th and the 95th percentile. Obesity is defined by a BMI-z equal to or greater than the 95th percentile.
Assessment of change in responses to the sleep MEMAS questionnaire at different times of the study
时间窗: At baseline, at 1, 3, 6, 12 and 24 months of follow-up
This part of the questionnaire compiles items on the duration (in number of hours) and quality of sleep (from " very good " =1 to " very bad " =4). Items were included since the literature seems to point out a link between lack of sleep and obesity (Chaput \& Tremblay, 2012; Chen et al., 2008; Fatima et al., 2015; Patel \& Hu, 2008).
Participant's clinical informations
时间窗: At baseline (inclusion)
Several participant's clinical informations will be collected : recruitment center, inpatient or outpatient status, main diagnosis (DSM-5), comorbidities, second generation antipsychotic prescribed and its dosage, co-medication type and dosage. In order to create an equivalence between the doses of APs received, a conversion to an equivalent dose of chlorpromazine will be carried out according to published standards (Woods et al., 2003).
Family metabolic informations
时间窗: At baseline (inclusion)
Presence or not of obesity, dyslipidemia, diabetes and gestational diabetes, high blood pressure, cardiovascular disease in parents will be asked ; and reported weight (in kilograms) and height (in meters) of the parents will be collected (but not measured).
Assessment of change of prolactin level at different times of the study
时间窗: At baseline, at 3, 12 and 24 months of follow-up
Laboratory testing includes prolactin level with normal range between 5 to 20 ng/mL.
Assessment of change of waist circumference at different times of the study
时间窗: At baseline, at 1, 2, 3, 6, 9, 12 and 24 months of follow-up
Waist circumference (centimeters) will be taken using the same instruments and according to a standardized technique. The waist circumference percentiles will be calculated according to established Canadian standards for age and sex (Katzmarzyk et al., 2004).
Assessment of change of fasting lipids level at different times of the study
时间窗: At baseline, at 3, 6, 12 and 24 months of follow-up
The threshold values (mmol/L) for fasting lipids are those recommended by the National Cholesterol Education Program (NCEP, 1992), grouped into commonly used categories (Cook et al., 2003) : total cholesterol \> 5.15; LDL \>3.34; non-HDL cholesterol \>3.73; HDL \>1.04; triglycerides (0-9 years) \>1.12; triglycerides \>1.46 (10-19 years).
Assessment of change of fasting glucose level at different times of the study
时间窗: At baseline, at 3, 6, 12 and 24 months of follow-up
Laboratory testing includes fasting blood sugar. Diabetes will be defined according to the criteria (fasting glucose ≥ 0.7 mmol/L with confirmation by other test) established by the American Diabetes Association (ADA, 2004).
Assessment of change of fasting insulinemia level at different times of the study
时间窗: At baseline, at 3, 6, 12 and 24 months of follow-up
Laboratory testing includes fasting insulinemia level. Insulin resistance will be estimated with the Homeostasis Model Assessment Insulin - Resistance Index (HOMA-IR) = \[Insulin (µUI/ml) x glucose (mg/dl)/405\] (Matthews et al., 1985). The threshold value of 2.28 will define insulin resistance (Tresaco et al., 2005).
Assessment of change of alanine aminotransferase (ALT) level at different times of the study
时间窗: At baseline, at 6, 12 and 24 months of follow-up
Laboratory testing includes alanine aminotransferase level with normal range between 5 to 40 U/L.
Assessment of change in responses to the physical activity MEMAS questionnaire at different times of the study
时间窗: At baseline, at 1, 3, 6, 12 and 24 months of follow-up
This self-questionnaire using a compilation of different validated items obtained from the United States Youth Risk Behavior Surveillance System (Brener et al, 2013), from Patient-centered Assessment and Counseling for Exercise + Nutrition, a 2-item validated questionnaire for adolescent physical activity (Hardie Murphy et al, 2015; Prochaska et al, 2001) and also include questions on the perception of self-efficacy during exercise (Motl et al, 2000). Screen time questions collect the number of hours spent during weekdays/ends (Schmitz et al, 2004). Items about transportation to school were adapted from the questionnaire of the Canadian branch of the Health Behavior in School-aged Children (Currie et al, 2010; Gropp et al, 2013). Time spent outdoors outside of school hours is evaluated by the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE)(LeBlanc et al, 2015; Katzmarzyk et al,2013), items are rated from 0 (strongly disagree) to 4 (very much agree).
次要结局
未报告次要终点
研究者
Leila Ben Amor
Clinical Professor
St. Justine's Hospital