Diagnostic Utility of Attention Deficit Hyperactivity Disorder (ADHD) by Brain Activity Flow Patterns Analysis Using Evoked Response Potentials

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01063153
• Collaborator: ElMindA Ltd (Industry)
• Enrollment: 71
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

The purpose of this research study is to study a device called an electroencephalograph (EEG) in the diagnosis of treatment of attention deficit hyperactivity disorder (ADHD) in adults. People with ADHD have symptoms such as difficulty sustaining attention, organizing, and managing impulsivity. They can have trouble in school, at work, and at home. Subjects with ADHD who participate in this study will be given a once daily stimulant medication called osmotic release methylphenidate (Concerta) for 6 weeks, and have EEG testing done before and after the treatment period. Subjects will perform a computer based cognitive task during EEG testing. The U.S. Food and Drug Administration has approved osmotic release methylphenidate (Concerta) for the treatment of ADHD in adults and children. Similar procedures, without medication, will be performed with a sample of healthy adults without ADHD.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: Osmotic Release Methylphenidate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Diagnostic Utility of ADHD by Brain Activity Flow Patterns Analysis Using Evoked Response Potentials
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Concerta Open-Label Concerta (Osmotic Release Methylphenidate)	Drug: Osmotic Release Methylphenidate; During a 6 week treatment period, adult subjects with ADHD are prescribed, in an open label fashion, once daily doses of osmotic release methylphenidate to a maximum daily dose of 144 mg. Efficacy and tolerability assessments are completed, in addition to EEG and cognitive testing. Healthy adults without ADHD will not receive medication.; Other Names: Concerta
No Intervention: Control group Healthy subjects without ADHD will be assessed using EEG.

Outcome Measures

Primary Outcome Measures

1. Adult ADHD Investigator Symptom Rating Scale (AISRS) [Baseline and 6 weeks]

   An 18-item scale rating a subject's level of impairment from 0 (none) to 3 (severe) for each symptom of DSM-IV ADHD, with a maximum possible score of 54. The measure was collected at Baseline and 6 weeks, and a total score was calculated to gauge treatment response of ADHD subjects to open-label Concerta.

2. Percent Errors in Visual Go/NoGo Task [Single Point (Baseline)]

   The Go/NoGo visual task was completed by subjects with ADHD as well as healthy controls. The Go/NoGo task is used to assess inhibitory control, and targets response inhibition, executive functions, and sustained attention. The 'Go' stimulus occupies 80% of the trials, and requires the subject to perform a motor response each time it appears on the screen. A rare 'No Go' stimulus (occupies 20% of all trials) requires the subject to refrain from responding. The percentage of errors were measured for each group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

ADHD Subjects

Inclusion Criteria:

• Male and female outpatients, aged 18-55 years

• Subjects meeting full criteria for the diagnosis of DSM-IV (Diagnostic and Statistical Manual, Version 4) Attention Deficit Hyperactivity Disorder (ADHD)

• Absence of pharmacological treatment for ADHD for at least one week.

• Right handedness

Exclusion Criteria:

• Any other current psychiatric or medical condition determined to be clinically significant.

• Current use of psychotropics or any medication with clinically significant CNS (Central Nervous System) effects.

• Mental retardation (IQ < 80).

• Significant sensory deficits such as deafness or blindness.

• Individuals with a history of substance dependence or abuse within the past 6 months.

• Pregnant or nursing females.

• Subjects with pre-existing structural cardiac abnormalities.

• Clinically significant abnormal laboratory values, electrocardiogram or blood pressure reading

Healthy Control Subjects

Inclusion Criteria:

• Males and females, aged 18-55 years

• Subjects who do not meet full criteria for the diagnosis of DSM-IV Attention Deficit Hyperactivity Disorder (ADHD), as determined by clinical evaluation and/or ADHD module of structured diagnostic interview, completed by the study clinician.

• Right handedness

Exclusion Criteria:

• Any current psychiatric or medical condition determined to be clinically significant.

• Current use of psychotropics or any medication with clinically significant CNS effects.

• Mental retardation (IQ < 80).

• Significant sensory deficits such as deafness or blindness.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• ElMindA Ltd

Investigators

• Principal Investigator: Joseph Biederman, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joseph Biederman, MD, Chief, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01063153
• Other Study ID Numbers: 2009-P-000174
• First Posted: Feb 5, 2010
• Last Update Posted: May 3, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Joseph Biederman, MD, Chief, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital: ADHD; Adults; Electroencephalography (EEG); Concerta
• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Methylphenidate

Study Results

Participant Flow

Arm/Group Title	Control	ADHD
Arm/Group Description	Controls without ADHD were assessed using EEG	Subjects with ADHD were assessed with EEG before and after treatment with Concerta
Period Title: Overall Study
STARTED	33	38
COMPLETED	31	26
NOT COMPLETED	2	12

Baseline Characteristics

Arm/Group Title	Control	ADHD	Total
Arm/Group Description	Subjects without ADHD	Subjects with ADHD	Total of all reporting groups
Overall Participants	33	38	71
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	33 100%	38 100%	71 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.2 (11.0)	35.5 (10.5)	34.0 (10.8)
Sex: Female, Male (Count of Participants)
Female	16 48.5%	14 36.8%	30 42.3%
Male	17 51.5%	24 63.2%	41 57.7%
Region of Enrollment (participants) [Number]
United States	33 100%	38 100%	71 100%

Outcome Measures

1. Primary Outcome

Title	Adult ADHD Investigator Symptom Rating Scale (AISRS)
Description	An 18-item scale rating a subject's level of impairment from 0 (none) to 3 (severe) for each symptom of DSM-IV ADHD, with a maximum possible score of 54. The measure was collected at Baseline and 6 weeks, and a total score was calculated to gauge treatment response of ADHD subjects to open-label Concerta.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Subjects in the ADHD group who completed all 6 weeks of the trial were included in data analysis. Subjects who completed at least 3 weeks of treatment were also included regardless of the reason for withdrawal, and final-visit AISRS scores were used in ITT (intent-to-treat) analysis via last observation carried forward [LOCF] imputation.

Arm/Group Title	ADHD	Controls
Arm/Group Description	Subjects with ADHD were assessed before and after treatment.	Controls without ADHD were assessed with a one-time EEG, only.
Measure Participants	28	0
Baseline	37.0 (8.7)
6 weeks	15.0 (9.4)

2. Primary Outcome

Title	Percent Errors in Visual Go/NoGo Task
Description	The Go/NoGo visual task was completed by subjects with ADHD as well as healthy controls. The Go/NoGo task is used to assess inhibitory control, and targets response inhibition, executive functions, and sustained attention. The 'Go' stimulus occupies 80% of the trials, and requires the subject to perform a motor response each time it appears on the screen. A rare 'No Go' stimulus (occupies 20% of all trials) requires the subject to refrain from responding. The percentage of errors were measured for each group.
Time Frame	Single Point (Baseline)

Outcome Measure Data

Analysis Population Description

Only subjects that met the a priori pre-defined EEG signal quality criteria were included.

Arm/Group Title	ADHD and Visual NoGo Task	Control Group and Visual NoGo Task	ADHD and Visual Go Task	Control Group and Visual Go Task
Arm/Group Description	Participants with a DSM-IV diagnosis of ADHD completed the NoGo Visual Task, in which they had to refrain from responding.	Participants without a DSM-IV diagnosis of ADHD completed the NoGo Visual Task, in which they had to refrain from responding.	Participants with a DSM-IV diagnosis of ADHD completed the Go Visual Task, in which they had to perform a motor response to a stimulus.	Participants without a DSM-IV diagnosis of ADHD completed the Go Visual Task, in which they had to perform a motor response to a stimulus.
Measure Participants	26	27	30	26
Number [percentage of errors]	19.01	13.89	2.88	1.27

Adverse Events

Arm/Group Title	Control		ADHD
Arm/Group Description	Subjects without ADHD were assessed using EEG.		Subjects with ADHD were assessed with EEG before and after open-label treatment with Concerta.
All Cause Mortality
	Control		ADHD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Control		ADHD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Control		ADHD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		22/38 (57.9%)
Cardiac disorders
Racing Heart	0/33 (0%)	0	3/38 (7.9%)	5
Gastrointestinal disorders
Gastrointestinal Upset	0/33 (0%)	0	3/38 (7.9%)	3
General disorders
Dry Mouth	0/33 (0%)	0	2/38 (5.3%)	5
Headache	0/33 (0%)	0	11/38 (28.9%)	19
Increased Energy	0/33 (0%)	0	3/38 (7.9%)	5
Irritability	0/33 (0%)	0	3/38 (7.9%)	7
Jitteriness	0/33 (0%)	0	4/38 (10.5%)	7
Tiredness	0/33 (0%)	0	4/38 (10.5%)	8
Metabolism and nutrition disorders
Decreased Appetite	0/33 (0%)	0	9/38 (23.7%)	20
Musculoskeletal and connective tissue disorders
Tension	0/33 (0%)	0	6/38 (15.8%)	10
Psychiatric disorders
Anxiety	0/33 (0%)	0	3/38 (7.9%)	3
Dulled Affect	0/33 (0%)	0	4/38 (10.5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Brain Network Analysis [the primary analysis of EEG data related to BAFPA (Brain Activity Flow Patterns Analysis) and functional connectivity networks] is still in progress by the Sponsor, and there is an agreement between the Sponsor and the Principal Investigator preventing the PI from disclosing EEG results from this trial until the data has been published. We are, however, at liberty to report adverse events from the open-label clinical trial and have done so here.