Omega-3 Fatty Acid Supplementation to ADHD Pharmacotherapy in ADHD Adults With Deficient Emotional Self-Regulation Traits

Study Overview
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Brief Summary
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The purpose of this study is to a) assess the efficacy of omega-3 fatty acids in the treatment of Deficient Emotional Self-Regulation (DESR) among stimulant treated Attention Deficit Hyperactivity Disorder (ADHD) adults, b) assess the side effect profile of omega-3 fatty acids in the treatment of DESR among stimulant treated ADHD adults, c) assess effects of omega-3 fatty acid supplementation on ADHD symptoms and associated features in stimulant treated ADHD adults, and d) predict value of fatty acids present in red blood cell membranes. This study will be a 12-week trial with adults 18-55 years of age with ADHD and symptoms of DESR.

Official Title
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Omega-3 Fatty Acid Supplementation to ADHD Pharmacotherapy in ADHD Adults With DESR Traits: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Conditions
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Attention Deficit Hyperactivity Disorder (ADHD), Deficient Emotional Self-Regulation (DESR)

Intervention / Treatment
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* Drug: ADHD Medication
* Drug: Omega-3 Fatty Acids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female adults ages 18-55 years. A diagnosis of childhood onset Attention Deficit Hyperactivity Disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) based on clinical assessment. Childhood onset will be defined according to established research criteria, requiring onset of two symptoms of inattentive or of impulsive/hyperactive traits by the age of 12. A score of 24 or more on the Adult ADHD Investigator Symptom Report Scale (AISRS), or, for those individuals stably treated with a medication approved by the Food and Drug Administration for ADHD, a Clinical Global Impression (CGI) ADHD severity score of no greater than 4 (moderately ill). Those subjects treated with traditional ADHD pharmacotherapy must be on a stable, effective dose (per clinician evaluation) of an FDA-approved treatment for ADHD for at least one month at the time of enrollment. A Deficient Emotional Self Regulation (DESR) T-score on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Emotional Control Scale of at least 65 and/or a score of 99 or more on the DESR. Exclusion Criteria For those subjects not treated for their ADHD at the time of enrollment, a history of non-response or intolerance to methylphenidate at adequate doses as determined by the clinician. A history of intolerance to omega-3 fatty acids as determined by the clinician. Pregnant or nursing females. Serious, unstable medical illness including hepatic, renal, gastroenterological, respiratory, cardiovascular, endocrinologic (thyroid), neurologic (seizure), immunologic, or hematologic disease. Glaucoma. Clinically unstable psychiatric conditions including suicidality, homicidality, bipolar disorder, psychosis, or lifetime history of a clinically serious condition potentially exacerbated by a stimulant such as mania, or psychosis. Tics or a family history or diagnosis of Tourette's syndrome. Current (within 3 months) DSM-IV criteria for abuse or dependence with any psychoactive substance other than nicotine. Allergies to fish or shellfish; multiple adverse drug reactions. Any other concomitant medication with primarily central nervous system activity other than specified in Concomitant Medication portion of the protocol. Current use of Monoamine Oxidase (MAO) Inhibitor or use within the past two weeks. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Omega-3 Fatty Acids<br>1060 mg EPA Omega-3 Fatty Acids | Drug: ADHD Medication<br>* For those subjects not on stable ADHD treatment (defined as a stable, effective dose for at least one month, determined by the study clinician, of a medication that is FDA approved to treat ADHD), OROS-Methylphenidate will be openly prescribed. Subjects on a stable dose of medication for ADHD will be instructed to continue on their current dose of medication.<br>* Other names: Dexmethylphenidate;Drug: Omega-3 Fatty Acids<br>* Omega-3 Fatty Acids prescribed to participants randomized to active medication. They may be randomized to receive 1060mg of EPA (2 capsules containing 530mg EPA and 137mg DHA). Dosage will remain constant throughout study.<br>* Other names: Nordic Natural EPA Xtra;|
| Placebo Comparator: Placebo<br> | Drug: ADHD Medication<br>* For those subjects not on stable ADHD treatment (defined as a stable, effective dose for at least one month, determined by the study clinician, of a medication that is FDA approved to treat ADHD), OROS-Methylphenidate will be openly prescribed. Subjects on a stable dose of medication for ADHD will be instructed to continue on their current dose of medication.<br>* Other names: Dexmethylphenidate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Endpoint on the BRIEF-A Emotional Control Scale | The BRIEF-A is a 75-item questionnaire that assesses and adult's cognitive, emotional, and behavioral functions within the past month. The subject rates each question on a 3-point scale (1=Never, 2=Sometimes, 3=Often). Raw scores are calculated and used to generate T-scores for 8 scales (Inhibit, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials), 2 summary index scales (Behavioral Regulation Index and Metacognition Index), and one scale reflecting overall functioning (Global Executive Composite). T-scores range from 30 to 100, with scores ≥65 indicating clinical impairment. A reduction in score indicates improvement. | Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Measured by Mean Change From Baseline to Endpoint on Adult ADHD Investigator Rating Scale (AISRS) Total Score | The Adult ADHD Investigator Rating Scale (AISRS) measures ADHD symptoms in adults. This scale is an investigator rated scale. Higher scores on this scale indicate more severe ADHD-like symptoms. Patients symptoms are rated as never, rarely, sometimes, often, or very often by the investigator. Total score ranges from 0 to 54. T-scores range from 30 to 100, with scores ≥65 indicating clinical impairment. A reduction in score indicates improvement. | baseline to 12 weeks | 
| Efficacy Measured by Mean Change From Baseline to Endpoint on Clinical Global Impression (CGI) Scale | The Clinical Global Impression (CGI) is a 3-item observer-rated scale that measures illness severity (CGIS), global improvement or change (CGIC) and therapeutic response (CGIE). Scores range from 0 to 7 on each subscale. Total scores range from 0 to 21. T-scores range from 30 to 100, with scores ≥65 indicating clinical impairment. A reduction in score indicates improvement. | baseline to 12 weeks | 
| Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | The BRIEF-A is a 75-item questionnaire that assesses and adult's cognitive, emotional, and behavioral functions within the past month. The subject rates each question on a 3-point scale (1=Never, 2=Sometimes, 3=Often). Raw scores are calculated and used to generate T-scores for 8 scales (Inhibit, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials), 2 summary index scales (Behavioral Regulation Index and Metacognition Index), and one scale reflecting overall functioning (Global Executive Composite). T-scores range from 30 to 100, with scores ≥65 indicating clinical impairment. A reduction in score indicates improvement. | baseline to 12 weeks | 
| Efficacy Measured by Mean Change From Baseline to Endpoint on the Global Assessment of Functioning (GAF) Scale | The Global Assessment of Functioning (GAF) scale is used to rate how serious a mental illness may be. Lower scores on this scale indicate a lower level of functioning and higher severity of symptoms. Total scores range from 0 to 100. | baseline to 12 weeks |