Attention Deficit/Hyperactivity Disorder (ADHD)
Conditions
Keywords
ADHD, inattentive, impulsive, hyperactive, poor academic performance, poor self-discipline, low self-esteem
Brief summary
The primary objective of this trial is to determine whether an oral administration of Phosphatidylserine-Omega3 would significantly improve the clinical symptoms of children suffering from ADHD. Both the behavior and the academic achievements aspects will be evaluated. In addition, we intend to measure side-effects and adverse events and to examine the possible correlation between biochemical and behavioral alterations.
Detailed description
This study is a single-center, double-blind, randomized, placebo-controlled 15-weeks duration trial to assess safety and efficacy of Phosphatidylserine-Omega3 in children diagnosed with ADHD, according to the DSM-IV. Following screening, the subjects will be randomized to one of two treatment groups:Phosphatidylserine-Omega3 or placebo, in a 2:1 manner. This will be followed by an open-label extension, in which Phosphatidylserine-Omega3 will be administered to all eligible participants. Primary measures of attention and behavior will be evaluated using Conners Rating Scale (CRS) teacher- rating scales. As a secondary endpoint, the attention and behavior will be measured by CRS and strength and difficulties questionnaires (SDQ) parental- and SDQ teacher-rating scales, assessment a continuous performance test (TOVA), and parental Child Health questionnaire (CHQ). Improvement in ADHD symptoms will be evaluated by Clinical Global of Impression - Improvement (CGI-I). Finally, tolerability will be monitored using Barkley Side Effects Rating Scale (SERS) and biochemical parameters, such as fatty acid profile and monoamines metabolites will be assessed as well.
Interventions
OTHERColored cellulose tainted with fishy odor
as arm 1
DIETARY_SUPPLEMENTPhosphatidylserine-Omega3
Phosphatidylserine-Omega3 conjugate capsules. Weeks 0-15: 300 mg/day. weeks 16-30: 150 mg/day and a 150 mg/day one year follow-up.
Sponsors
Enzymotec
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 13 Years
Healthy volunteers
No
Inclusion criteria
1. Parental written informed consent. 2. Having a teacher that is familiar with the child and parent and willing to participate. 3. Age: 13≥ years ≥6 4. Gender: male and female 5. Diagnosis: ADHD diagnosed by: Teacher-rated Attention-Deficit/ Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) School Version at least 1.5 standard deviations (SD) above the norm for the patient's age and gender, Confirmed assessment by Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), 6. Clinical Global Impression of Severity of illness (CGI-S) rating of 4 or higher (moderately ill or worse), 7. Language: Subjects, parents, and teachers must be able to read, write and speak Hebrew 8. Normal weight and height according to the Israeli standards 9. Attending full-time to school.
Exclusion criteria
1. Females who had reached menarche and presented three regular menstrual cycles; the definition of regular menstrual cycles: an average length of the cycle between 22 and 41 days, either none or a single cycle with a length less than 22 or more than 41 days during the past year 2. History or current diagnosis of any serious systemic (e.g., diabetes, hyper/hypothyroidism, etc.) or neurological condition (e.g., epilepsy, brain tumors, etc.) 3. Failed to respond to 2 or more adequate courses (dose and duration) of stimulant therapy for ADHD 4. Pervasive developmental disorder or Non-verbal Learning Disability 5. Schizophrenia, or other psychotic disorders (DSM-IV axis I) 6. Any evidence of suicidal risk, any current psychiatric comorbidity that required psychiatric pharmacotherapy 7. History of alcohol or substance abuse as defined by DSM-IV criteria 8. Consumption of \>250 mg/day of caffeine 9. Blindness 10. History of allergic reactions or sensitivity to marine products (fish and seafood), soy or corn as well as any illness which may jeopardize the participants health or limit their successful trial completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Conners Rating Scale - School Version | change from baseline in conners raiting scale at 15 weeks | A questionnaire that assesses symptoms of ADHD in children and adolescents according to the DSM-IV guidelines. It consists of questions on classroom behavior. Based on the questionnaire results, subscales and global indexes are calculated, including restless-impulsive index, emotional lability index and hyperactive/impulsive subscale. The lowest scale score is 40 (best)and the highest is 90 (worse). Usually, a score below 62 is considered normal and a score above 62 is considered abnormal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Strength and Difficulties Questionnaires - School Version | on weeks 0,15 | — |
| Strength and Difficulties Questionnaires - Home Version | on weeks 0,15 | — |
| Clinical Global Impression of Improvement | on weeks 0,15 | — |
| Test of Variables of Attention (TOVA) | on weeks 0,15 | — |
| Child Health Questionnaire (CHQ)- Parent-completed Form 50 | on weeks 0,15 | — |
| Plasma and Red Blood Cells Fatty Acid Profile | on weeks 0,15 | — |
| Conners Rating Scale - Home Version | change from baseline in conners raiting scale at 15 weeks | A questionnaire that assesses symptoms of ADHD in children and adolescents according to the DSM-IV guidelines. It consists of questions on the childs home behavior. Based on the questionnaire results, subscales and global indexes are calculated, including restless-impulsive index, emotional lability index and hyperactive/impulsive subscale. The lowest scale score is 40 (best)and the highest is 90 (worse). Usually, a score below 62 is considered normal and a score above 62 is considered abnormal. |
| Vital Signs | on weeks 0,15 | — |
| Essential Fatty Acid (EFA)-Deficiency Symptoms | on weeks 0,15 | — |
| Barkley Side Effects Rating Scale (SERS) | on weeks 0,15 | — |
| Complete Blood Counts | on weeks 0,15 | — |
| Biochemical Parameters in Blood - Liver Functions (SGPT, SGOT, Total Bilirubin), Kidney Functions (BUN, Creatinine), Na, K, Cl, Ca | on weeks 0,15 | — |
| Lipid Profile (Cholesterol, HDL, Triglycerides) | on weeks 0,15 | — |
| Blood Monoamines Metabolism | on week 0, 15 | — |
Countries
Israel
Participant flow
Recruitment details
Children at the age of 6-13 years were screened at the Geha mental health center, Israel, for participation in the study. Recruitment of participants was achieved by vast advertisement in newspapers, internet and in practitioners clinics. Participants enrollment period March 2007 to March 2008
Participants by arm
| Arm | Count |
|---|---|
| PS Omega 3 Conjugate The daily dosage consisted of 4 capsules of PS-Omega3, providing 300 mg Phosphatidylserine per day. | 137 |
| Placebo Double-blind: Cellulose (4 capsules per day). Open-label: PS-omega3 | 63 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Phase | Adverse Event | 2 | 1 |
| Double-blind Phase | Poor compliance | 3 | 1 |
| Double-blind Phase | Withdrawal by Subject | 22 | 9 |
Baseline characteristics
| Characteristic | PS Omega 3 Conjugate | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 9.10 years STANDARD_DEVIATION 1.89 | 9.24 years STANDARD_DEVIATION 1.77 | 9.15 years STANDARD_DEVIATION 1.85 |
| Clinical Global Impression of Severity (CGI-S) Extremely seriously ill (score 6) | 4 Participants | 0 Participants | 4 Participants |
| Clinical Global Impression of Severity (CGI-S) Moderately ill (score 4) | 83 Participants | 36 Participants | 119 Participants |
| Clinical Global Impression of Severity (CGI-S) Seriously ill (score 5) | 50 Participants | 27 Participants | 77 Participants |
| Sex: Female, Male Female | 45 Participants | 22 Participants | 67 Participants |
| Sex: Female, Male Male | 92 Participants | 41 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 137 | 1 / 63 |
| serious Total, serious adverse events | 0 / 137 | 0 / 63 |
Outcome results
Primary
Conners Rating Scale - School Version
A questionnaire that assesses symptoms of ADHD in children and adolescents according to the DSM-IV guidelines. It consists of questions on classroom behavior. Based on the questionnaire results, subscales and global indexes are calculated, including restless-impulsive index, emotional lability index and hyperactive/impulsive subscale. The lowest scale score is 40 (best)and the highest is 90 (worse). Usually, a score below 62 is considered normal and a score above 62 is considered abnormal.
Time frame: change from baseline in conners raiting scale at 15 weeks
Population: The analysis includes per-protocol (PP) population. Out of the 162 children who completed the study, 15 children were excluded from PP analysis due to low compliance or protocol violation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PS Omega 3 Conjugate | Conners Rating Scale - School Version | Conners Global index: Emotional Lability | -2.63 Scores on a scale | Standard Error 1.18 |
| PS Omega 3 Conjugate | Conners Rating Scale - School Version | Hyperactivity-impulsivity | -0.62 Scores on a scale | Standard Error 1.09 |
| PS Omega 3 Conjugate | Conners Rating Scale - School Version | Conners Global Index: restless impulsivity | -0.44 Scores on a scale | Standard Error 1.04 |
| Placebo | Conners Rating Scale - School Version | Conners Global Index: restless impulsivity | -1.73 Scores on a scale | Standard Error 1.67 |
| Placebo | Conners Rating Scale - School Version | Conners Global index: Emotional Lability | -0.63 Scores on a scale | Standard Error 1.77 |
| Placebo | Conners Rating Scale - School Version | Hyperactivity-impulsivity | -0.46 Scores on a scale | Standard Error 1.25 |
Secondary
Barkley Side Effects Rating Scale (SERS)
Time frame: on weeks 0,15
Secondary
Biochemical Parameters in Blood - Liver Functions (SGPT, SGOT, Total Bilirubin), Kidney Functions (BUN, Creatinine), Na, K, Cl, Ca
Time frame: on weeks 0,15
Secondary
Blood Monoamines Metabolism
Time frame: on week 0, 15
Secondary
Child Health Questionnaire (CHQ)- Parent-completed Form 50
Time frame: on weeks 0,15
Secondary
Clinical Global Impression of Improvement
Time frame: on weeks 0,15
Secondary
Complete Blood Counts
Time frame: on weeks 0,15
Secondary
Conners Rating Scale - Home Version
A questionnaire that assesses symptoms of ADHD in children and adolescents according to the DSM-IV guidelines. It consists of questions on the childs home behavior. Based on the questionnaire results, subscales and global indexes are calculated, including restless-impulsive index, emotional lability index and hyperactive/impulsive subscale. The lowest scale score is 40 (best)and the highest is 90 (worse). Usually, a score below 62 is considered normal and a score above 62 is considered abnormal.
Time frame: change from baseline in conners raiting scale at 15 weeks
Population: The analysis includes per-protocol (PP) population. Out of the 162 children who completed the study, 15 children were excluded from PP analysis due to low compliance or protocol violation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PS Omega 3 Conjugate | Conners Rating Scale - Home Version | Conner's Global restless-impulsivity | -5.19 Scores on a scale | Standard Error 1 |
| PS Omega 3 Conjugate | Conners Rating Scale - Home Version | Conner's Global Index:Emotional lability | -3.54 Scores on a scale | Standard Error 1.08 |
| PS Omega 3 Conjugate | Conners Rating Scale - Home Version | DSM-IV: Hperactivity impulsivity | -4.23 Scores on a scale | Standard Error 1.15 |
| Placebo | Conners Rating Scale - Home Version | Conner's Global restless-impulsivity | -1.71 Scores on a scale | Standard Error 1.72 |
| Placebo | Conners Rating Scale - Home Version | Conner's Global Index:Emotional lability | -5.56 Scores on a scale | Standard Error 1.8 |
| Placebo | Conners Rating Scale - Home Version | DSM-IV: Hperactivity impulsivity | -2.62 Scores on a scale | Standard Error 1.77 |
Secondary
Essential Fatty Acid (EFA)-Deficiency Symptoms
Time frame: on weeks 0,15
Secondary
Lipid Profile (Cholesterol, HDL, Triglycerides)
Time frame: on weeks 0,15
Secondary
Plasma and Red Blood Cells Fatty Acid Profile
Time frame: on weeks 0,15
Secondary
Strength and Difficulties Questionnaires - Home Version
Time frame: on weeks 0,15
Secondary
Strength and Difficulties Questionnaires - School Version
Time frame: on weeks 0,15
Secondary
Test of Variables of Attention (TOVA)
Time frame: on weeks 0,15
Secondary
Vital Signs
Time frame: on weeks 0,15