The Efficacy and Safety of Phosphatidylserine-Omega3 in Children With Attention-Deficit/ Hyperactivity Disorder

• ClinicalTrials.gov Identifier: NCT00418184
• Recruitment Status: Completed
• First Posted: January 4, 2007
• Results First Posted: February 26, 2010
• Last Update Posted: March 12, 2014
• Sponsor: Enzymotec
• Information provided by: Enzymotec

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Attention Deficit/Hyperactivity Disorder (ADHD)	Dietary Supplement: Phosphatidylserine-Omega3; Other: Colored cellulose tainted with fishy odor	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of The Efficacy and Safety of Phosphatidylserine-Omega3 in Children With Attention-Deficit/ Hyperactivity Disorder
• Study Start Date: March 2007
• Actual Primary Completion Date: November 2008
• Actual Study Completion Date: November 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Dietary Supplement: Phosphatidylserine-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.
Placebo Comparator: 2	Other: Colored cellulose tainted with fishy odor; as arm 1

Outcome Measures

Primary Outcome Measures :

1. Conners Rating Scale - School Version [ Time Frame: 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 Outcome Measures :

1. Conners Rating Scale - Home Version [ Time Frame: 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.
2. Strength and Difficulties Questionnaires - School Version [ Time Frame: on weeks 0,15 ]
3. Strength and Difficulties Questionnaires - Home Version [ Time Frame: on weeks 0,15 ]
4. Clinical Global Impression of Improvement [ Time Frame: on weeks 0,15 ]
5. Test of Variables of Attention (TOVA) [ Time Frame: on weeks 0,15 ]
6. Child Health Questionnaire (CHQ)- Parent-completed Form 50 [ Time Frame: on weeks 0,15 ]
7. Plasma and Red Blood Cells Fatty Acid Profile [ Time Frame: on weeks 0,15 ]
8. Blood Monoamines Metabolism [ Time Frame: on week 0, 15 ]
9. Vital Signs [ Time Frame: on weeks 0,15 ]
10. Essential Fatty Acid (EFA)-Deficiency Symptoms [ Time Frame: on weeks 0,15 ]
11. Barkley Side Effects Rating Scale (SERS) [ Time Frame: on weeks 0,15 ]
12. Complete Blood Counts [ Time Frame: on weeks 0,15 ]
13. Biochemical Parameters in Blood - Liver Functions (SGPT, SGOT, Total Bilirubin), Kidney Functions (BUN, Creatinine), Na, K, Cl, Ca [ Time Frame: on weeks 0,15 ]
14. Lipid Profile (Cholesterol, HDL, Triglycerides) [ Time Frame: on weeks 0,15 ]

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 13 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Israel

ADHD Unit

Petach-Tiqva, Israel, 49100

Sponsors and Collaborators

Enzymotec

Investigators

• Study Director: Abraham Weizman, MD; Head of the Research Department, Geha Mental Health Center, Rabin Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Manor I, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman A. The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension. Eur Psychiatry. 2012 Jul;27(5):335-42. doi: 10.1016/j.eurpsy.2011.05.004. Epub 2011 Jul 31.

• Responsible Party: Manor Yonatan, Enzymotec LTD
• ClinicalTrials.gov Identifier: NCT00418184
• Other Study ID Numbers: PS-Omega3-2
• First Posted: January 4, 2007
• Results First Posted: February 26, 2010
• Last Update Posted: March 12, 2014
• Last Verified: January 2010

Keywords provided by Enzymotec:

ADHD; inattentive; impulsive; hyperactive; poor academic performance; poor self-discipline; low self-esteem

Additional relevant MeSH terms:

Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases