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

Genetic Modulation of Functional Brain Activity of Attention-deficit/Hyperactivity Disorder-related Working Memory Processes

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.

Study Overview

• Status: Completed
• Conditions: ADHD
• Intervention / Treatment: Drug: Placebo; Drug: Methylphenidate, non-retard

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Würzburg, Germany
    • Clinic for Psychiatrie, Psychosomatics and Psychotherapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: methylphenidate, non-retard	Drug: Methylphenidate, non-retard; Medication (methylphenidate, non-retard) will be titrated to optimal response within 6 weeks, with a maximum of 10 mg/day in week 1, 20 mg/day in week 2, 30 mg/day in week 3, 40 mg/day in week 4, 50 mg/day in week 5, and 60 mg/day in week 6, unless adverse effects emerged. After successful adjustment, medication will be maintained until week 6. Dosing will be based on at least two-weekly evaluations by a psychiatrist, including an interview with a review of symptoms and side effects, completion of the Clinical Global Impression (CGI) scale and completion of a standardised Side Effects Rating Scale for psychostimulants (SERS). The maximal daily dosage of MPH is 60 mg. Within this double blind study the same procedure is applied for the placebo condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Activation	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.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychology	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.	6 weeks
ADHD Core Symptoms: Measured by Conners Adult ADHD Rating Scales (CAARS), Inattention Scale	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	6 weeks

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Collaborators: German Research Foundation

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: April 29, 2011
• First Submitted That Met QC Criteria: May 9, 2011
• First Posted (Estimated): May 10, 2011

Study Record Updates

• Last Update Posted (Actual): August 15, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; 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: W004PS0108_1