Genetic Modulation of Working Memory in Attention Deficit Hyperactivity Disorder (ADHD)

Phase 3

Completed

Conditions: ADHD

Interventions: Drug: Placebo
Drug: Methylphenidate, non-retard

Registration Number: NCT01351272

Lead Sponsor: Wuerzburg University Hospital

Brief Summary: In this study the investigators will measure the functional brain activity of adult Attention Deficit Hyperactivity Disorder (ADHD) patients, genotyped according to the COMT genotype, during a Working Memory Paradigm, before and after a placebo controlled treatment with MPH for 6 WEEKS. Within this design, the investigators will be able to evaluate the therapeutic effect of MPH treatment on cognitive functions.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

Inclusion Criteria

Only participants will be included who (1) fulfil the diagnostic criteria defined in guidelines for the diagnosis of ADHD in childhood and adulthood and who (2) would be treated with MPH also for clinical indications outside the study.
Provision of written informed consent
A diagnosis of a ADHD (314.xx) by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV)
Females and males aged 18-50 years
Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrolment
Able to understand and comply with the requirements of the study
Right-handed according Edinburgh Handedness Inventory (Oldfield, 1971)
German as first language
Caucasian ethnicity

Exclusion Criteria

Pregnancy or lactation; women capable of childbearing are required to use a reliable method (Pearl-index < 1%) of contraception (e.g. hormonal treatment, intrauterine device, vasoligation in the partner, sexual abstinent)
Any current DSM-IV Axis I disorder not defined in the inclusion criteria requiring current additional treatment
Motoric tics, siblings with tics or positive family history or diagnosis of a Tourette syndrome
Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
Known intolerance or lack of response to methylphenidate, as judged by the investigator
Present pre-treatment with methylphenidate (within the last three month prior to study treatment)
Intake of MAO-inhibitors within the last 14 days prior to study treatment
Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
Unstable or inadequately treated medical illness (e.g. Congestive Heart Failure / CHF, angina pectoris, hypertension, narrow angle glaucoma, hyperthyroidism, thyreotoxicosis, cardiac arrhythmia, cardiac infarction) as judged by the investigator.
Epilepsy
An absolute neutrophil count (ANC) of minor 1.5 x 10 exp 9 per litre
Involvement in the planning and conduct of the study
Previous enrolment or randomisation of treatment in the present study
Participation in another drug trial within 4 weeks prior to enrolment into this study
Moderate, severe, or profound mental retardation
Heart pacemakers, cochlea implants, other metal parts in the head outside the mouth

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
methylphenidate, non-retard	Methylphenidate, non-retard	-

Primary Outcome Measures

Name	Time	Method
Brain Activation	6 weeks	Functional brain activity in right Superior Frontal Gyrus (SFG) during the working memory task post treatment as measured by fMRI. For each participant and conditions the estimated parameters are metric, and can be further analysed with ANOVAs or t-tests.

Secondary Outcome Measures

Name	Time	Method
ADHD Core Symptoms: Measured by Conners Adult ADHD Rating Scales (CAARS), Inattention Scale	6 weeks	Changes in CAARS scale ( T-values, 50 indicates the population mean with a standard deviation of 10) from pre to post. Higher T values indicate higher symptoms. T-score over 60 indicates clinically relevant ADHS symptoms More negative values of the difference indicate higher symptom reduction, therefore a better outcome. Range of T-values for pre and post measurements between 35 and 90, potential range for differences -55 to +55
Neuropsychology	6 weeks	Accuracy for the working memory paradigm at post. Accuracy was defined as the ratio of correct responses (correctly pressed and correctly not pressed) to total number of stimuli. Higher values indicate better perfromance.The theoretical range goes from 0 to 1.