LAMAinDiab - Lisdexamphetamine Vs Methylphenidate for Pediatric Patients with ADHD and Type 1 Diabetes - a Randomized Cross-over Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Change in ADHD symptom scores on the "inattention" scale of the Conners 3 questionnaire
研究概览
简要总结
This clinical trial aims to evaluate the safety and effectiveness of an intervention involving parental training in behaviour management and medication in children with both Type 1 Diabetes (T1D) and Attention Deficit Disorder with Hyperactivity (ADHD). ADHD is a neurodevelopmental disorder that affects around 5% of school-age children and adolescents, while T1D is a chronic disease requiring strict management.
After initial parental training provided for parents/legal guardians, the children will be randomized to one of two cross-over groups, and treated with either lisdexamfetamine or methylphenidate first. After dose optimization for first 5-7 weeks, patients will be treated for 6 months total, after which they will be switched to the other drug.
Researchers will then compare the ADHD symptom severity as measured by Conners 3 questionnaire, and compare the frequency of any adverse events associated with the therapy. As secondary outcomes, patient's T1D control and quality of life will be compared between the two drugs.
详细描述
This is a multicenter, randomized, open-label, cross-over 2nd phase clinical trial in children and adolescents with attention deficit disorder with hyperactivity (ADHD) and type 1 diabetes mellitus (T1D), conducted in four Polish reference pediatric diabetes centers that together provide care for around 25% of Polish pediatric population with T1D.
T1D is a chronic pediatric disorder that requires intensive treatment with subcutaneous insulin, constant monitoring and frequent decision-making from the patient. Its course may be further complicated by comorbidities such as ADHD, which is present in around 5% of general population and reportedly more common in those with T1D. Despite the recognized need for psychiatric screening in children with T1D, ADHD often remains undiagnosed and untreated, resulting in worse therapy adherence and glycemic control, as well increased risk of life-threatening acute diabetes complications.
Each patient will begin the trial starting with the enrollment appointment, followed by a baseline assessment by a diabetologist and a psychological evaluation. After 2-weeks preliminary observation period, the parents/legal guardians of the patient will start a cycle of 10 meetings (one every week, 90 minutes long). Patients will be enrolled in an online once-weekly parental training in behavior management (PT) for ten weeks. The PT will be carried out in small groups (4-6 families per session) and conducted by a qualified and experienced PT therapist and supplemented with homework and educational materials. Qualification for pharmacological treatment will be carried out for those patients who complete the entire PT cycle, defined as the presence of at least 8 out of 10 meetings confirmed by the trainer. This is the designated expert threshold at which an intervention can be considered as carried out correctly. If the parents/legal guardians do not hold the required number of meetings, they will be allowed to make up for the missing classes during the next series of meetings with another group. If the parents/legal guardians do not attend the missing activities during this trial, the child will be excluded from the study.
After completion of PT, each participant will repeat the psychological evaluation to assess the effects of PT intervention alone on ADHD symptoms severity. Those with sustained clinically-significant ADHD symptoms will be qualified for pharmacological intervention. The patient's will be evaluated on diabetologists visit for contraindications to pharmacotherapy, including urine tests (pregnancy and panel test for substance use), ECG with QT segment assessment (to exclude long QT syndrome) and ophthalmological consultation (to exclude glaucoma). Subsequent and final assessment and qualification will be performed by psychiatrist during the nearest online consultation, after which patients will be randomized to pharmacotherapy groups: methylphenidate (MPH, long-release capsule, standard of care) versus lisdexamfetamine (LDX, investigated treatment).
Dose escalation for each drug will be performed over three (up to four) psychiatric consultations during the initial 5-7 weeks. LDX will be started with 30mg once-daily, administered orally, with dose change increment of 20mg every (after 1st, 3rd, 5th and 7th week, to the maximum of 70mg). MPH will be started with 18mg once-daily, administered orally, with dose change incremental of 18mg (after 1st, 3rd, 5th and 7th week, to the maximum of 54mg).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
ADHD symptoms assessment will be performed with teleconsultation with outcomes assessor blinded for patient's allocation. Patients and their parents/legal guardians will be asked to not share the information with the assessor.
入排标准
- 年龄范围
- 8 Years 至 198 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Methylphenidate first, lisdexamfetamine second
Initial treatment after PT training - methylphenidate (prolonged-release tablet) once-daily with dose optimization for 5-7 weeks and 6 months total therapy then change to lisdexamfetamine once-daily with dose optimization for 5-7 weeks and 6 months total therapy.
干预措施: parental training in behavior management (Behavioral)
Methylphenidate first, lisdexamfetamine second
Initial treatment after PT training - methylphenidate (prolonged-release tablet) once-daily with dose optimization for 5-7 weeks and 6 months total therapy then change to lisdexamfetamine once-daily with dose optimization for 5-7 weeks and 6 months total therapy.
干预措施: Methylphenidate (Drug)
Lisdexamfetamine first, methylphenidate second
Initial treatment after PT training - lisdexamfetamine once-daily with dose optimization for 5-7 weeks and 6 months total therapy then change to methylphenidate (prolonged-release tablet) once-daily with dose optimization for 5-7 weeks and 6 months total therapy.
干预措施: parental training in behavior management (Behavioral)
Lisdexamfetamine first, methylphenidate second
Initial treatment after PT training - lisdexamfetamine once-daily with dose optimization for 5-7 weeks and 6 months total therapy then change to methylphenidate (prolonged-release tablet) once-daily with dose optimization for 5-7 weeks and 6 months total therapy.
干预措施: Lisdexamfetamine (Drug)
结局指标
主要结局
Change in ADHD symptom scores on the "inattention" scale of the Conners 3 questionnaire
时间窗: Before pharmacotherapy (after completion of PT training) and the end of the 6-month course of pharmacotherapy with LDX or MPH; similar difference (before pharmacotherapy and after 6 months of therapy) for the other drug
Change of ADHD symptom severity, measured as the difference in ADHD symptom score on the "inattention" scale of the Conners 3 questionnaire (completed by patient and parent/legal guardian), assessed by the investigator blinded to patient allocation.
Change in ADHD symptom scores on the "hyperactivity/impulsivity" scale of the Conners 3 questionnaire
时间窗: Before pharmacotherapy (after completion of PT training) and the end of the 6-month course of pharmacotherapy with LDX or MPH; similar difference (before pharmacotherapy and after 6 months of therapy) for the other drug
Change of ADHD symptom severity, measured as the difference in ADHD symptom score on the "hyperactivity/impulsivity" scale of the Conners 3 questionnaire (completed by patient and parent/legal guardian), assessed by the investigator blinded to patient allocation.
The number of adverse events - methylphenidate arm
时间窗: Events recorded throughout treatment with MPH for 6 months after randomization or cross-over
The number of adverse events coded following the MedDRA dictionary.
The frequency of adverse events - methylphenidate arm
时间窗: Events recorded throughout treatment with MPH for 6 months after randomization or cross-over.
The frequency of adverse events per patient-month coded following the MedDRA dictionary.
The number of adverse events - lisdexamphetamine arm
时间窗: Events recorded throughout treatment with LDX for 6 months after randomization or cross-over
The number of adverse events coded following the MedDRA dictionary.
The frequency of adverse events - lisdexamphetamine arm
时间窗: Events recorded throughout treatment with LDX for 6 months after randomization or cross-over
The frequency of adverse events per patient-month coded following the MedDRA dictionary.
次要结局
- Change in Type 1 Diabetes Mellitus metabolic control - glycated haemoglobin(Measured after 6 months of MPH or LDX treatment and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration))
- Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived percentage percentage time above target range >250mg/dL (significant hyperglycemia)(Measured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days))
- Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived percentage percentage time in target range 70-180mg/dL(Measured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days))
- Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived percentage percentage time below target range <70mg/dL (hypoglycemia)(MMeasured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days))
- Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived percentage percentage time above target range >180mg/dL (hyperglycemia)(Measured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days))
- Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived percentage percentage time below target range <54mg/dL (clinically significant hypoglycemia)(Measured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days))
- Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived mean sensor glucose(Measured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days))
- Percentage of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "inattention" scale(Measured before pharmacotherapy (after completion of PT training) and the end of the 6-month course of pharmacotherapy with LDX or MPH; similar difference (before pharmacotherapy and after 6 months of therapy) for the other drug)
- Change in Type 1 Diabetes Mellitus metabolic control - CGM-derived coefficient of variation(Measured after 6 months of MPH or LDX treatment (using last 14 days before visit) and compared to the measurement before pharmacotherapy (after PT training, week 10th/22nd depending on PT duration, using data from 14 preceding days))
- Improvement of the patient's quality of life (QoL)(Improvement of the patient's quality of life (QoL) measured from baseline (within 2 weeks before PT training), after completion of PT training (week 10th/22nd) and after each 6 months of pharmacotherapy arm)
- Number of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "inattention" scale(Measured before pharmacotherapy (after completion of PT training) and the end of the 6-month course of pharmacotherapy with LDX or MPH; similar difference (before pharmacotherapy and after 6 months of therapy) for the other drug)
- Number of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "hyperactivity/impulsivity" scale(Measured before pharmacotherapy (after completion of PT training) and the end of the 6-month course of pharmacotherapy with LDX or MPH; similar difference (before pharmacotherapy and after 6 months of therapy) for the other drug)
- Percentage of trial participants achieving an improvement in ADHD symptom severity on the basis of Conners 3 "hyperactivity/impulsivity" scale(Measured before pharmacotherapy (after completion of PT training) and the end of the 6-month course of pharmacotherapy with LDX or MPH; similar difference (before pharmacotherapy and after 6 months of therapy) for the other drug)