Attention Deficit Hyperactivity Disorder (ADHD), Deficient Emotional Self-Regulation (DESR)
Conditions
Brief summary
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.
Interventions
DRUGADHD Medication
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.
DRUGOmega-3 Fatty Acids
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.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female adults ages 18-55 years. 2. 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. 3. 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. 4. 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
1. 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. 2. A history of intolerance to omega-3 fatty acids as determined by the clinician. 3. Pregnant or nursing females. 4. Serious, unstable medical illness including hepatic, renal, gastroenterological, respiratory, cardiovascular, endocrinologic (thyroid), neurologic (seizure), immunologic, or hematologic disease. 5. Glaucoma. 6. 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. 7. Tics or a family history or diagnosis of Tourette's syndrome. 8. Current (within 3 months) DSM-IV criteria for abuse or dependence with any psychoactive substance other than nicotine. 9. Allergies to fish or shellfish; multiple adverse drug reactions. 10. Any other concomitant medication with primarily central nervous system activity other than specified in Concomitant Medication portion of the protocol. 11. Current use of Monoamine Oxidase (MAO) Inhibitor or use within the past two weeks. 12. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Endpoint on the BRIEF-A Emotional Control Scale | Baseline to 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Measured by Mean Change From Baseline to Endpoint on Adult ADHD Investigator Rating Scale (AISRS) Total Score | baseline to 12 weeks | 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. |
| Efficacy Measured by Mean Change From Baseline to Endpoint on Clinical Global Impression (CGI) Scale | baseline to 12 weeks | 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. |
| Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | baseline to 12 weeks | 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. |
| Efficacy Measured by Mean Change From Baseline to Endpoint on the Global Assessment of Functioning (GAF) Scale | baseline to 12 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omega-3 Fatty Acids 1060 mg EPA Omega-3 Fatty Acids
ADHD Medication: 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.
Omega-3 Fatty Acids: 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. | 1 |
| Placebo ADHD Medication: 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. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Omega-3 Fatty Acids | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Continuous | 48 years | 21 years | 34.5 years STANDARD_DEVIATION 19.09 |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
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.
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omega-3 Fatty Acids | Mean Change From Baseline to Endpoint on the BRIEF-A Emotional Control Scale | -7 T-Score |
| Placebo | Mean Change From Baseline to Endpoint on the BRIEF-A Emotional Control Scale | -33 T-Score |
Secondary
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.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on Adult ADHD Investigator Rating Scale (AISRS) Total Score | -14 T-Score |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on Adult ADHD Investigator Rating Scale (AISRS) Total Score | -23 T-Score |
Secondary
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.
Time frame: baseline to 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A BRI Scale T-Scores from Baseline | -7 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Plan/Organize Scale T-Scores fro | -11 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Shift Scale T-Scores from Baseli | 0 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A MI Scale T-Scores from Baseline | -12 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Self Monitor Scale T-Scores from | 0 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A GEC Scale T-Scores from Baseline | -11 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Initiate Scale T-Scores from Bas | -17 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Inhibit Scale T-Scores from Base | -14 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Task Monitor Scale T-Scores from | -5 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Working Memory Scale T-Scores fr | -11 units on a scale |
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Organization of Materials Scale | -6 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Shift Scale T-Scores from Baseli | -13 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Organization of Materials Scale | -22 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Inhibit Scale T-Scores from Base | -28 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Self Monitor Scale T-Scores from | -13 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Initiate Scale T-Scores from Bas | -9 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Working Memory Scale T-Scores fr | -30 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A BRI Scale T-Scores from Baseline | -29 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A MI Scale T-Scores from Baseline | -46 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A GEC Scale T-Scores from Baseline | -29 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Plan/Organize Scale T-Scores fro | -19 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on BRIEF-A Subscales | Change in BRIEF-A Task Monitor Scale T-Scores from | -32 units on a scale |
Secondary
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.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on Clinical Global Impression (CGI) Scale | 5 T-Score |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on Clinical Global Impression (CGI) Scale | 1 T-Score |
Secondary
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.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omega-3 Fatty Acids | Efficacy Measured by Mean Change From Baseline to Endpoint on the Global Assessment of Functioning (GAF) Scale | 11 units on a scale |
| Placebo | Efficacy Measured by Mean Change From Baseline to Endpoint on the Global Assessment of Functioning (GAF) Scale | 8 units on a scale |