Brain Connectivity in Attention Deficit Hyperactivity Disorder (ADHD) (BCADHD)

Brain Connectivity in Attention Deficit Hyperactivity Disorder (ADHD): a Biomarker to Predict Treatment Response

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

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
• Intervention / Treatment: Drug: MPH

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 8AF
    • King's College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo, 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.	Drug: MPH; Participants undergo behavioural tests and brain scanning twice, once under placebo and once under an acute dose of MPH, before starting long-term treatment with a long-acting formulation of MPH used routinely at the Adult ADHD Clinic.; Other Names: Methylphenidate
Experimental: MPH, Placebo; 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.	Drug: MPH; Participants undergo behavioural tests and brain scanning twice, once under placebo and once under an acute dose of MPH, before starting long-term treatment with a long-acting formulation of MPH used routinely at the Adult ADHD Clinic.; Other Names: Methylphenidate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	In the month 2-3 following the last scan.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	In the month 4-5 following the last scan.
Diffusion imaging-based measurements as statistically significant predictors of treatment response defined by a data-driven approach.	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.	In the month 6-7 following the last scan.
Functional connectivity measurements as statistically significant predictors of treatment response as defined by a data-driven approach.	Treatment response is defined as in outcome 3.	In the month 8-9 following the last scan.

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: Shire
• Investigators: Study Director: Declan Murphy, MD, PhD, King's College London

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2013
• Primary Completion (Actual): January 15, 2015
• Study Completion (Actual): March 10, 2016

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): October 17, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: biomarker; longitudinal study; stimulant medication; magnetic resonance imaging (MRI); treatment response; methylphenidate; brain connectivity
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: ConnectADHD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No