Clinical trial NCT03709940: Brain Connectivity in Attention Deficit Hyperactivity Disorder (ADHD)
Official title: Brain Connectivity in Attention Deficit Hyperactivity Disorder (ADHD): a Biomarker to Predict Treatment Response
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Keywords: longitudinal study
magnetic resonance imaging (MRI)
brain connectivity
biomarker
treatment response
methylphenidate
stimulant medication
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: Shire
First posted: 2018-10-17
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 30 participants with Attention Deficit Hyperactivity Disorder (ADHD) undergo behavioural tests and brain scanning twice, once under placebo and once under an acute dose of methylphenidate (MPH). The order of the tablets is inverted for the second half of the sample, thus the last 30 participants undergo behavioural tests and brain scanning twice, once under an acute dose of MPH and once under placebo. All 60 participants are then treated with a long-acting formulation of MPH used routinely at the Adult ADHD Clinic.
Primary purpose: OTHER

Brief summary: This study investigates whether a relationship exists between pre-treatment brain characteristics and treatment response in adults with Attention Deficit Hyperactivity Disorder (ADHD).

Detailed description: There is a pressing need in psychiatry to offer more individualised treatments, and to improve outcomes from clinical trials. This 'individualised medicine' approach requires the development of biomarkers of treatment response.

60 adults with ADHD are recruited from the Adult ADHD Clinic at the Maudsley Hospital, London, United Kingdom.

The study is developed over three sessions, two at baseline (DAY 1 and DAY 2) and one after two months of treatment (follow-up).

The first two sessions are conceived as a single-blind non-randomised placebo-controlled cross-over experiment. The first 30 participants enrolled in the study receive a placebo tablet (ascorbic acid 50 mgs) on DAY 1 before the behavioural assessment and magnetic resonance imaging (MRI) scan. The behavioural assessment and the functional MRI measurements are repeated two days after (DAY 2), under a clinically effective dose (20 mgs) of short-acting methylphenidate (MPH).

The order of the tablets is reverted for the remaining 30 participants to balance any potential expectation and practice effect between the two conditions. Placebo and medication are over-encapsulated with the same red opaque capsules by the pharmacy team. Also, the protocol followed during the two sessions is absolutely identical in respect of timing and tests administered in order to keep the participants blind to the drug condition (medication or placebo).

After the scanning sessions, all the participants receive the same prescription of a long-acting formulation of MPH, according to the clinical guidelines adopted by the Maudsley Hospital. Treatment response is evaluated clinically and behaviourally after 2 months of treatment (follow-up). Pre-treatment brain characteristics are tested as potential predictors (biomarkers) of treatment response.

Eligibility criteria: Inclusion Criteria:

* males
* aged 18-45 years old
* intelligent quotient (IQ) \> 70 (as measured by WASI)
* diagnosis of ADHD confirmed through clinical assessment (Adult ADHD Clinic)
* non-medicated (stimulant medication-naive or not taking stimulant medication for at least 4 weeks)

Exclusion Criteria:

* no other brain disorders other than ADHD
* no condition precluding MRI scanning (e.g., metallic implants, claustrophobia)

Primary outcomes:
measure: Diffusion imaging-based measurements as statistically significant predictors of treatment response (i.e. of participants' performance on adult ADHD rating scale at follow-up as compared to baseline).
timeFrame: In the month 2-3 following the last scan.
Secondary outcomes:
measure: Functional connectivity measurements as statistically significant predictors of treatment response (i.e. of participants' performance on adult ADHD rating scale at follow-up as compared to baseline).
timeFrame: In the month 4-5 following the last scan.
measure: Diffusion imaging-based measurements as statistically significant predictors of treatment response defined by a data-driven approach.
timeFrame: In the month 6-7 following the last scan.
measure: Functional connectivity measurements as statistically significant predictors of treatment response as defined by a data-driven approach.
timeFrame: In the month 8-9 following the last scan.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College London
Study officials:
affiliation: King's College London
name: Declan Murphy, MD, PhD
role: STUDY_DIRECTOR
References: