Brain Connectivity in Attention Deficit Hyperactivity Disorder (ADHD)
- Conditions
- Attention Deficit Hyperactivity Disorder (ADHD)
- Interventions
- Registration Number
- NCT03709940
- Lead Sponsor
- King's College London
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 60
- 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)
- no other brain disorders other than ADHD
- no condition precluding MRI scanning (e.g., metallic implants, claustrophobia)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo, MPH MPH Dose order: placebo, methylphenidate (MPH) Participants receive a placebo tablet (ascorbic acid 50 mgs) on DAY 1 and a clinically effective dose of short-acting MPH (20 mgs) on DAY 2. MPH, Placebo MPH Dose order: methylphenidate (MPH), placebo Participants receive a clinically effective dose of short-acting MPH (20 mgs) on DAY 1 and a placebo tablet (ascorbic acid 50 mgs) on DAY 2.
- Primary Outcome Measures
Name Time Method 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). In the month 2-3 following the last scan. Diffusion based measurements include specific measures of anatomical connectivity of pathways originating in the frontal lobes, such as the fronto-striatal pathways and the superior longitudinal fasciculus. According to previously published criteria, treatment response is defined as a symptomatic improvement of at least 30%, as measured by participants' performance on adult ADHD rating scale at follow-up as compared to baseline.
- Secondary Outcome Measures
Name Time Method Functional connectivity measurements as statistically significant predictors of treatment response as defined by a data-driven approach. In the month 8-9 following the last scan. Treatment response is defined as in outcome 3.
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). In the month 4-5 following the last scan. Functional connectivity measurements include the strength of functional connectivity along pathways originating in the frontal lobes, such as the fronto-striatal pathways and the attentive networks. Treatment response is defined as in outcome 1.
Diffusion imaging-based measurements as statistically significant predictors of treatment response defined by a data-driven approach. In the month 6-7 following the last scan. A categorical approach (data-driven analysis using multivariate k-mean clustering) is used to define treatment response on the basis of clinical and behavioural characteristics at follow-up. Clinical characteristics include participants' performance on adult ADHD rating scale at follow-up as compared to baseline, whereas behavioural characteristics include participants' performance on the Qb test at follow-up as compared to baseline.
Trial Locations
- Locations (1)
King's College London
🇬🇧London, United Kingdom