Effects of Modulation of the Dopaminergic System Using Methylphenidate on Memory and Executive Processes in Individuals With 22q11.2 Deletion Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Stroop task
研究概览
简要总结
Chromosome 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated with a high risk of psychiatric disorders, including schizophrenia spectrum disorders. This population is characterized by a specific neurocognitive profile and atypical brain development. Methylphenidate is a psychostimulant used in the treatment of attention deficit with/without hyperactivity (ADHD). Although ADHD is one of the most important co-morbidities in 22q11DS, affecting 35-45% of patients, to date only two studies have focused on quantifying the efficacy of this treatment in this population. The objective of this study is to quantify the improvement in cognitive performance as well as the differences in brain connectivity associated with the methylphenidate molecule in a population at risk of cognitive impairment and the development of schizophrenia.
详细描述
This study aimed to investigate the effects of methylphenidate (Concerta ®) in patients with 22q11DS. Outcome is evaluated based on changes in clinical and cognitive measures as well as brain connectivity (with magnetic resonance imaging and electroencephalography). Treatment benefits are evaluated in an intra-subject design, i.e. performance with/without treatment are compared for each patient. Depending on medication history and current psychostimulant medication, participants are included either in the consumer group (composed of participants with ongoing methylphenidate treatment) or in the naïve group (composed of participants naïve to the molecule). To the naive participants the investigators prescribe a 13-day treatment of Concerta ® at a weight-adjusted dose of 0.7 mg/kg). The treatment phase begins with a lower introductory dose for the first 5 days before moving on to the weight-adjusted dose. The effect of treatment on cognitive measures is assessed on day 6, with memory monitoring on days 7 and 13. The treatment effect evaluated using clinical measures and questionnaires was conducted at the end of the treatment phase to ensure multiple opportunities for observation by the participant and caregivers. For consumer participants, the procedure was similar. For visits with methylphenidate, participants will be asked to take their usual prescription. In order to best follow the procedure of the naïve group, for the visits without methylphenidate, the consumer participants were asked to interrupt their usual prescription for 13 days. Since many participants usually interrupt their treatment during vacations or sometimes on weekends, compliance is not a barrier. For methylphenidate-free visits, a 5-day break prior to assessment with cognitive measures will be requested from each participant. Again, in order to ensure several opportunities for observation for the participant and caregivers, assessments with clinical measures and questionnaires will be conducted at the end of the break, on day 13.
The research hypothesis of this study is that methylphenidate treatment has a beneficial effect on clinical and cognitive performance. Scores in the tests evaluating these areas are expected to be significantly better than when the tests were administered in the absence of the substance. A change in brain connectivity is also expected when the drug is taken, tending towards a "normalization" of brain connectivity. Finally, to find the link between changes in cognitive measures and changes in brain connectivity is investigated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female with confirmed 22q11DS diagnosis.
- •Minimum age of 8 years or maximum age of 25 years and 11 months.
- •Attention difficulties pointed out by parents and/or the participant.
- •Sufficient verbal expression and comprehension skills to understand and follow instructions based on initial interview.
排除标准
- •Participants younger than 8 years and older that 25 years and 11 months.
- •Previous adverse experience with MPH
- •Cardio-vascular diseases including rhythm disorders, severe hypertension, cardiac insufficiency, obliterating cardiac and peripheral arterial disease, preexisting cerebrovascular affections, hemodynamically significant congenital heart defect, channelopathies.
- •For the naïve group only: corrected QT (QTc) distance at baseline electrocardiogram above 460 milliseconds or elongation at control electrocardiogram (Day 6 of treatment) superior to 30 milliseconds with functional complaint.
- •Psychiatric affections including anxiety attack, psychic tension or restlessness, manic episode, marked psychotic symptoms, schizophrenia, borderline personality disorder, clinical depression (present or past), suicidal episode, diagnosis or family history of Tourette syndrome, alcohol or drug abuse.
- •Other somatic affections including hyperthyroid, glaucoma, pheochromocytoma.
- •Concurrent treatment with monoamine oxidase inhibitors or interruption less than 14 days before beginning of treatment.
- •Pregnancy or breastfeeding.
研究组 & 干预措施
22q11DS naive
22q11DS participants naive to methylphenidate
干预措施: Concerta (Drug)
22q11DS consumer
22q11DS participants with a prolonged treatment of methylphenidate
干预措施: Concerta (Drug)
结局指标
主要结局
Stroop task
时间窗: Stroop inhibition ratio one month after the end of treatment
To measure the cost of cognitive inhibition in time, an inhibition ratio score is computed by dividing the raw score from the Stroop condition (participants have to name the color of the ink even though the word spells a different color) by the raw score in the color naming condition (participants are instructed to name rectangles of colors as fast as possible). This score reflects the cognitive cost of inhibiting the reading process. A ratio value close to 1 indicates a lesser cost of inhibition.
Letter-number sequencing
时间窗: Letter-number Sequencing one month after the end of treatment
A working memory subtest of the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Intelligence Scale for Children (WISC) in which the participant must sequence a random order of numbers and letters. Specifically, the participant must first say the numbers in ascending order and then the letters in alphabetical order. Longest sequence of letters and numbers correctly ordered
Cambridge Neuropsychological Test Automated Battery (CANTAB)
时间窗: CANTAB one month after the end of treatment
The Motor Screening test (MOT) is a training procedure designed screen for difficulties with vision, movement, or comprehension and ascertains that the subject can follow simple instructions, as well as familiarising them with the touch screen. Intra-Extra Dimensional Set Shift (IED) is a test of rule acquisition and reversal. It features visual discrimination and attentional set formation maintenance, shifting and flexibility of attention. Spatial Working Memory (SWM) is a test of the subject's ability to retain spatial information and to manipulate remembered items in working memory. It is a self-ordered task, which also assesses heuristic strategy. Stop Signal Task (SST) is a classic stop signal response inhibition test, which uses staircase functions to generate an estimate of stop signal reaction time. This test gives a measure of an individual's ability to inhibit a prepotent response.
Conners' Continuous performance test, third edition (CPT-3)
时间窗: CPT-3 one month after the end of treatment
Participants are instructed to press a button every time a letter appeared on the screen, except for the letter X where participants had to withhold their answer. Variables of interest are Detectability, Omission, Commission, Perseveration, Hit Reaction Time, Hit Reaction time Standard Deviation, Variability, Hit Reaction Time Block Change and Hit Reaction Time Inter- Stimulus Intervals Change.
Color Trails test (CTT)
时间窗: CTT flexibility ratio one month after the end of treatment
To measure the cost of task switching, a flexibility ratio was calculated to account for processing speed by dividing the time to complete part B (drawing a line between number following chronological order while alternating between colors) by time to complete part A (drawing a line between number following chronological order). Value closer to 1 indicate better flexibility.
15 signes & 15 words
时间窗: 15 signes & 15 words one month after the end of treatment
15 signs \& 15 words is a homemade episodic memory task inspired by the Rey Auditory Verbal Learning Test (Rey, 1958). Participants are required to learn 15 common French words and 15 signs (drawings made out of 1 or 2 basic geometrical forms). After delays of thirty minutes, one day, one week and one month, participants are asked to freely recall the words and the signs they remembered. They are also asked to recognize the target items form a list of distractors. Variables of interest are (1) learning score = Maximum number of items correctly recalled during learning divided by the number of trials to reach learning criterion. Low score indicates poor learning. (2) Retention % thirty minutes/on day/one week = Number of items recalled after each delay in time divided by the maximum of items recalled during learning. Low score indicates poor memory.
ADHD symptoms
时间窗: ADHD symptoms one month after the end of treatment
Diagnostic and Statistical Manual of Mental Disorders - fifth edition (DSM-V)
次要结局
- Magnetic Resonance Imaging (MRI) T1-weighted(MRI T1-weighted one month after the end of treatment)
- MRI Spectroscopy(MRI Spectroscopy one month after the end of treatment)
- MRI Resting State(MRI resting state one month after the end of treatment)
- MRI Diffusion weighted images(MRI DSI one month after the end of treatment)
- Electroencephalography (EEG) resting state(EEG resting state one month after the end of treatment)
- EEG auditory(EEG Auditory one month after the end of treatment)
- EEG visual(EEG Visual one month after the end of treatment)
- Behavior Rating Inventory of Executive Function (BRIEF) questionnaire(BRIEF one month after the end of treatment)
研究者
Stephan Eliez
Principal Investigator
University of Geneva, Switzerland