Effects of Methylphenidate on Brain and Cognition in 22q11 Deletion Syndrome

NCT04647500 | Completed

• 1 other identifier: PB_201601472
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

22q11.2 Deletion Syndrome

Outcome Measures

Primary Outcomes (21)

• Conners' Continuous performance test, third edition (CPT-3)

  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.

  CPT-3 pre-treatment

• Conners' Continuous performance test, third edition (CPT-3)

  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.

  CPT-3 6 days of treatment

• Conners' Continuous performance test, third edition (CPT-3)

  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.

  CPT-3 one month after the end of treatment

• Stroop task

  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.

  Stroop inhibition ratio pre-treatment

• Stroop task

  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.

  Stroop inhibition ratio 6 days of treatment

• Stroop task

  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.

  Stroop inhibition ratio one month after the end of treatment

• Letter-number sequencing

  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

  Letter-number Sequencing pre-treatment

• Letter-number sequencing

  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

  Letter-number Sequencing 6 days of treatment

• Letter-number sequencing

  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

  Letter-number Sequencing one month after the end of treatment

• Color Trails test (CTT)

  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.

  CTT flexibility ratio pre-treatment

• Color Trails test (CTT)

  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.

  CTT flexibility ratio 6 days of treatment

• Color Trails test (CTT)

  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.

  CTT flexibility ratio one month after the end of treatment

• Cambridge Neuropsychological Test Automated Battery (CANTAB)

  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.

  CANTAB pre-treatment

• Cambridge Neuropsychological Test Automated Battery (CANTAB)

  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.

  CANTAB 6 days of treatment

• Cambridge Neuropsychological Test Automated Battery (CANTAB)

  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.

  CANTAB one month after the end of treatment

• 15 signes & 15 words

  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.

  15 signes & 15 words pre-treatment

• 15 signes & 15 words

  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.

  15 signes & 15 words 6 days of treatment

• 15 signes & 15 words

  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.

  15 signes & 15 words one month after the end of treatment

• ADHD symptoms

  Diagnostic and Statistical Manual of Mental Disorders - fifth edition (DSM-V)

  ADHD symptoms pre-treatment

• ADHD symptoms

  Diagnostic and Statistical Manual of Mental Disorders - fifth edition (DSM-V)

  ADHD symptoms 13 days of treatment

• ADHD symptoms

  Diagnostic and Statistical Manual of Mental Disorders - fifth edition (DSM-V)

  ADHD symptoms one month after the end of treatment

Secondary Outcomes (24)

• Magnetic Resonance Imaging (MRI) T1-weighted

  MRI T1-weighted pre-treatment

• Magnetic Resonance Imaging (MRI) T1-weighted

  MRI T1-weighted 6 days of treatment

• Magnetic Resonance Imaging (MRI) T1-weighted

  MRI T1-weighted one month after the end of treatment

• MRI Spectroscopy

  MRI Spectroscopy pre-treatment

• MRI Spectroscopy

  MRI Spectroscopy 6 days of treatment

Other Outcomes (6)

• Sensory-motor conflict 1

  Synchrony condition pre-treatment

• Sensory-motor conflict 1

  Synchrony condition 6 days of treatment

• Sensory-motor conflict 1

  Synchrony condition one month after the end of treatment

Study Arms (2)

22q11DS naive

OTHER

22q11DS participants naive to methylphenidate

Drug: Concerta

22q11DS consumer

OTHER

22q11DS participants with a prolonged treatment of methylphenidate

Drug: Concerta

Interventions

Concerta DRUG

Evaluation of a treatment of Concerta over a period of 13 days.

22q11DS consumer; 22q11DS naive

Eligibility Criteria

• Age: 8 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Geneva, Switzerland: lead

Study Sites (1)

Developmental imaging and psychopathology lab

Geneva, 1204, Switzerland

Location

MeSH Terms

Conditions

DiGeorge Syndrome

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

22q11 Deletion Syndrome; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Lymphatic Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Stephan Eliez, Professor

  University of Geneva, faculty of medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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)

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: December 1, 2020
• Study Start: August 26, 2016
• Primary Completion: September 26, 2022
• Study Completion: September 26, 2022
• Last Updated: October 7, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)