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Efficacy of Phosphatidylserine Enriched With n-3 PUFA Supplementation on ADHD in Children With Epilepsy (AGPIn3)

Primary Purpose

Attention Deficit Disorder With Hyperactivity, ADHD Inattention or Mixed Type, Epilepsy

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Vayarin®, supplementation of n-3 PUFA
PLACEBO
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Attention Deficit Disorder With Hyperactivity focused on measuring Epilepsy, Attention Deficit Disorders, VAYARIN, Children, Polyunsaturated n-3 fatty acid supplementation

Eligibility Criteria

6 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Children aged 6 to 15 years and 11 months.
  • Children of either sex (male/female) suffering from epilepsy regardless of syndrome classification.
  • Subjects on a stable dose of antiepileptic drugs (AED) for at least one month prior to inclusion and subjects for whom no change is considered a priori for the three months following the inclusion.
  • Diagnosis of ADHD inattention or mixed type according to the DSM V criteria.
  • Subjects must agree to study participation and their parents/legal guardian must provide written inform consent prior to participation in the study.

Exclusion Criteria:

  • Subjects less than 6 years or older than 16 years old
  • AED not stable for at least one month and/or a change in AED is expected in the three months following inclusion.
  • Diagnosis of ADHD hyperactivity type exclusive according to DSM V criteria.
  • Mental retardation defined by a score < 70 on the verbal comprehension and perceptual reasoning Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV), performed within 18 months prior to inclusion or at V1.
  • Diagnosis of a psychiatric comorbidity other than ADHD according to the DSM V criteria, including: pervasive developmental disorders including autism disorders; bipolar disordersand psychotic disorders.
  • Children suffering from diabetes, any type.
  • Use of psychoactive drugs in ADHD within the previous month: Methylphenidate, Amphetamine, Atomoxetine, Modafinil and Antidepressants whatever the class.
  • Use of dietary supplementation, other than vitamins, within the last 3 months.
  • Use of ketogenic diet within the last 3 months.
  • Allergy to fish or other sea products.
  • Soy allergy.
  • Absence of coverage by social security.

Sites / Locations

  • CHU de Amiens
  • CHU d'Angers
  • Hôpital des Enfants - Pellegrin
  • CHRU Lille
  • Hospices Civils de Lyon
  • Hôpital de la Timone
  • Hôpital Necker-Enfants malades
  • Hôpital Robert-Debré
  • CHU de Rennes
  • Hôpital de Hautepierre
  • CHU de Toulouse
  • CHU de Tours
  • Hôpital Brabois - Rue du Morvan

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

PS-OMEGA 3, capsules twice daily

PLACEBO, capsules twice daily

Arm Description

Vayarin®, supplementation of n-3 PUFA: each capsule contains 8.5 mg of docosahexaenoic acid (DHA), 21.5 mg of eicosapentaenoic acid (EPA) and 75 mg of phosphatidylserine.

The placebo will be made of cellulose and a small amount of fish powder to maintain the double-blind in odor and taste. The supplementation in n-3 PUFA in the placebo group may be considered as negligible. Placebo will be administered as indistinguishable capsules, identical to the active product.

Outcomes

Primary Outcome Measures

Reduction of the ADHD-rating scale IV inattentive subscore in subjects assigned to supplementation of PS-Omega 3 in comparison with the placebo group after 12 weeks of treatment.
The ADHD Rating Scale-IV quantifies each of the 18 symptoms of ADHD on a 0 to 3 scale, with a maximum score of 54 points. Nine of the 18 items score for inattention while the nine others assess hyperactivity with a maximum of 27 points each. The discriminative value of these two subscales was validated, allowing their individual use.

Secondary Outcome Measures

Reduction of the ADHD Rating Scale-IV total score in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
The ADHD Rating Scale-IV quantifies each of the 18 symptoms of ADHD on a 0 to 3 scale, with a maximum score of 54 points.
Reduction of TOVA total score in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
The TOVA (Test of Variables of Attention) is a computerized tool assessing the capacity of attention and impulse control. This test has been validated as a diagnostic tool in ADHD.
Proportion of subjects with a normalized TOVA score in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
The TOVA (Test of Variables of Attention) is a computerized tool assessing the capacity of attention and impulse control. This test has been validated as a diagnostic tool in ADHD.
Change in quality of life score in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
Quality of life assessed by the EFIQUACEE questionnaire (Echelle Française d'Impact et de Qualité de Vie Chez l'Enfant atteint d'Epilepsie). The EFIQUACEE questionnaire is a unique quality of life scale for children suffering from epilepsy. It is validated in French language.
Evolution of plasma lipid profiles in subjects assigned to supplementation of PS-Omega 3 in comparison with the placebo group after 12 weeks of treatment.
Plasma levels before and after 12 weeks of treatment: total lipid mass ; total phospholipids ; individual phospholipids including: lysophosphatidylcholin, phosphatidylcholin, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol, lysophosphatidylethanolamine ; total triglycerides ; fatty acids profiles in phospholipids; fatty acids profiles in triglycerides ; fatty acids profiles in cholesterol esters.
Evolution of eythrocytes lipid profiles in subjects assigned to supplementation of PS-Omega 3 in comparison with the placebo group after 12 weeks of treatment.
Quantification of, in erythrocyte membrane, before and after 12 weeks of treatment: total lipid mass ; total phospholipids ; individual phospholipids including: lysophosphatidylcholin, phosphatidylcholin, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol, lysophosphatidylethanolamine ; total triglycerides ; fatty acids profiles in phospholipids; fatty acids profiles in triglycerides ; fatty acids profiles in cholesterol esters.
Tolerance of a supplementation of PS-Omega 3.
Tolerance analysis of the supplementation of PS-Omega 3: interrogatoire, phone calls, clinical examinations, adverse events reported throughout the study.
Number of subjects with a reduction in the frequency of seizures ≥ 50%, in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
After 24 weeks of treatment, description of the total score of ADHD Rating Scale.
After 24 weeks of treatment, description of the total score of TOVA.
After 24 weeks of treatment, proportion of subjects with a normalized TOVA score.
After 24 weeks of treatment, change in quality of life score (EFIQUACEE questionnaire).
After 24 weeks of treatment, plasma lipid levels before and after treatment.
Plasma levels before and after 24 weeks of treatment: total lipid mass ; total phospholipids ; individual phospholipids including: lysophosphatidylcholin, phosphatidylcholin, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol, lysophosphatidylethanolamine ; total triglycerides ; fatty acids profiles in phospholipids; fatty acids profiles in triglycerides ; fatty acids profiles in cholesterol esters.
After 24 weeks of treatment, erythrocyte lipid levels before and after treatment.
Quantification of, in erythrocyte membrane, before and after 24 weeks of treatment: total lipid mass ; total phospholipids ; individual phospholipids including: lysophosphatidylcholin, phosphatidylcholin, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol, lysophosphatidylethanolamine ; total triglycerides ; fatty acids profiles in phospholipids; fatty acids profiles in triglycerides ; fatty acids profiles in cholesterol esters.

Full Information

First Posted
January 22, 2015
Last Updated
March 6, 2019
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT02348073
Brief Title
Efficacy of Phosphatidylserine Enriched With n-3 PUFA Supplementation on ADHD in Children With Epilepsy
Acronym
AGPIn3
Official Title
Efficacy of Phosphatidylserine Enriched With Polyunsaturated n-3 Fatty Acid Supplementation on Attention Deficit Disorders in Children With Epilepsy. A Randomized Double-blind Placebo-controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
March 2015 (Actual)
Primary Completion Date
October 2018 (Actual)
Study Completion Date
October 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Our project aims to develop a new therapeutic approach in epilepsy-associated attention disorders in children, through evaluation of the clinical impact of dietary n-3 fatty acids, containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) conjugated to a phospholipid vector. The primary objective is to evaluate the efficacy of a PUFA supplementation (PS-Omega 3), after 12 weeks of treatment, on attention disorders in children with epilepsy. Secondary objectives include: To evaluate the impact of a supplementation of PS-Omega 3 on quality of life. To evaluate the impact of a supplementation of PS-Omega 3 on serum and erythrocyte lipid profiles. To assess the tolerance of a supplementation of PS-Omega 3. To assess the impact of a supplementation of PS-Omega 3 on the frequency of seizures. To describe the impact of a supplementation of PS-Omega 3, at 24 weeks, on attention disorders in children with epilepsy, on quality of life, and on serum and erythrocyte lipid profiles. This study will recruit 272 subjects aged 6- 16 years, suffering from epilepsy (any type) and attention deficit hyperactivity disorder (ADHD) (inattentive or combined type) according to DSM V criteria in 12 clinical sites in France.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention Deficit Disorder With Hyperactivity, ADHD Inattention or Mixed Type, Epilepsy, Child
Keywords
Epilepsy, Attention Deficit Disorders, VAYARIN, Children, Polyunsaturated n-3 fatty acid supplementation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
77 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PS-OMEGA 3, capsules twice daily
Arm Type
Active Comparator
Arm Description
Vayarin®, supplementation of n-3 PUFA: each capsule contains 8.5 mg of docosahexaenoic acid (DHA), 21.5 mg of eicosapentaenoic acid (EPA) and 75 mg of phosphatidylserine.
Arm Title
PLACEBO, capsules twice daily
Arm Type
Placebo Comparator
Arm Description
The placebo will be made of cellulose and a small amount of fish powder to maintain the double-blind in odor and taste. The supplementation in n-3 PUFA in the placebo group may be considered as negligible. Placebo will be administered as indistinguishable capsules, identical to the active product.
Intervention Type
Drug
Intervention Name(s)
Vayarin®, supplementation of n-3 PUFA
Intervention Description
Two capsules will be swallowed twice daily, 20 to 30 minutes prior to breakfast and dinner, during 12 weeks, between visit 1 and visit 2. At the end of this period, active product will be continued, at the same dose, for a 12 week-open label period. All patients will be administered the active product.
Intervention Type
Drug
Intervention Name(s)
PLACEBO
Intervention Description
Two capsules will be swallowed twice daily, 20 to 30 minutes prior to breakfast and dinner, during 12 weeks, between visit 1 and visit 2.
Primary Outcome Measure Information:
Title
Reduction of the ADHD-rating scale IV inattentive subscore in subjects assigned to supplementation of PS-Omega 3 in comparison with the placebo group after 12 weeks of treatment.
Description
The ADHD Rating Scale-IV quantifies each of the 18 symptoms of ADHD on a 0 to 3 scale, with a maximum score of 54 points. Nine of the 18 items score for inattention while the nine others assess hyperactivity with a maximum of 27 points each. The discriminative value of these two subscales was validated, allowing their individual use.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Reduction of the ADHD Rating Scale-IV total score in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
Description
The ADHD Rating Scale-IV quantifies each of the 18 symptoms of ADHD on a 0 to 3 scale, with a maximum score of 54 points.
Time Frame
12 weeks
Title
Reduction of TOVA total score in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
Description
The TOVA (Test of Variables of Attention) is a computerized tool assessing the capacity of attention and impulse control. This test has been validated as a diagnostic tool in ADHD.
Time Frame
12 weeks
Title
Proportion of subjects with a normalized TOVA score in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
Description
The TOVA (Test of Variables of Attention) is a computerized tool assessing the capacity of attention and impulse control. This test has been validated as a diagnostic tool in ADHD.
Time Frame
12 weeks
Title
Change in quality of life score in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
Description
Quality of life assessed by the EFIQUACEE questionnaire (Echelle Française d'Impact et de Qualité de Vie Chez l'Enfant atteint d'Epilepsie). The EFIQUACEE questionnaire is a unique quality of life scale for children suffering from epilepsy. It is validated in French language.
Time Frame
12 weeks
Title
Evolution of plasma lipid profiles in subjects assigned to supplementation of PS-Omega 3 in comparison with the placebo group after 12 weeks of treatment.
Description
Plasma levels before and after 12 weeks of treatment: total lipid mass ; total phospholipids ; individual phospholipids including: lysophosphatidylcholin, phosphatidylcholin, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol, lysophosphatidylethanolamine ; total triglycerides ; fatty acids profiles in phospholipids; fatty acids profiles in triglycerides ; fatty acids profiles in cholesterol esters.
Time Frame
12 weeks
Title
Evolution of eythrocytes lipid profiles in subjects assigned to supplementation of PS-Omega 3 in comparison with the placebo group after 12 weeks of treatment.
Description
Quantification of, in erythrocyte membrane, before and after 12 weeks of treatment: total lipid mass ; total phospholipids ; individual phospholipids including: lysophosphatidylcholin, phosphatidylcholin, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol, lysophosphatidylethanolamine ; total triglycerides ; fatty acids profiles in phospholipids; fatty acids profiles in triglycerides ; fatty acids profiles in cholesterol esters.
Time Frame
12 weeks
Title
Tolerance of a supplementation of PS-Omega 3.
Description
Tolerance analysis of the supplementation of PS-Omega 3: interrogatoire, phone calls, clinical examinations, adverse events reported throughout the study.
Time Frame
36 weeks
Title
Number of subjects with a reduction in the frequency of seizures ≥ 50%, in the PS-Omega 3 group compared with the placebo group after 12 weeks of treatment.
Time Frame
12 weeks
Title
After 24 weeks of treatment, description of the total score of ADHD Rating Scale.
Time Frame
24 weeks
Title
After 24 weeks of treatment, description of the total score of TOVA.
Time Frame
24 weeks
Title
After 24 weeks of treatment, proportion of subjects with a normalized TOVA score.
Time Frame
24 weeks
Title
After 24 weeks of treatment, change in quality of life score (EFIQUACEE questionnaire).
Time Frame
24 weeks
Title
After 24 weeks of treatment, plasma lipid levels before and after treatment.
Description
Plasma levels before and after 24 weeks of treatment: total lipid mass ; total phospholipids ; individual phospholipids including: lysophosphatidylcholin, phosphatidylcholin, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol, lysophosphatidylethanolamine ; total triglycerides ; fatty acids profiles in phospholipids; fatty acids profiles in triglycerides ; fatty acids profiles in cholesterol esters.
Time Frame
24 weeks
Title
After 24 weeks of treatment, erythrocyte lipid levels before and after treatment.
Description
Quantification of, in erythrocyte membrane, before and after 24 weeks of treatment: total lipid mass ; total phospholipids ; individual phospholipids including: lysophosphatidylcholin, phosphatidylcholin, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, diphosphatidylglycerol, lysophosphatidylethanolamine ; total triglycerides ; fatty acids profiles in phospholipids; fatty acids profiles in triglycerides ; fatty acids profiles in cholesterol esters.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children aged 6 to 15 years and 11 months. Children of either sex (male/female) suffering from epilepsy regardless of syndrome classification. Subjects on a stable dose of antiepileptic drugs (AED) for at least one month prior to inclusion and subjects for whom no change is considered a priori for the three months following the inclusion. Diagnosis of ADHD inattention or mixed type according to the DSM V criteria. Subjects must agree to study participation and their parents/legal guardian must provide written inform consent prior to participation in the study. Exclusion Criteria: Subjects less than 6 years or older than 16 years old AED not stable for at least one month and/or a change in AED is expected in the three months following inclusion. Diagnosis of ADHD hyperactivity type exclusive according to DSM V criteria. Mental retardation defined by a score < 70 on the verbal comprehension and perceptual reasoning Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV), performed within 18 months prior to inclusion or at V1. Diagnosis of a psychiatric comorbidity other than ADHD according to the DSM V criteria, including: pervasive developmental disorders including autism disorders; bipolar disordersand psychotic disorders. Children suffering from diabetes, any type. Use of psychoactive drugs in ADHD within the previous month: Methylphenidate, Amphetamine, Atomoxetine, Modafinil and Antidepressants whatever the class. Use of dietary supplementation, other than vitamins, within the last 3 months. Use of ketogenic diet within the last 3 months. Allergy to fish or other sea products. Soy allergy. Absence of coverage by social security.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sylvain Rheims, MD
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Amiens
City
Amiens
Country
France
Facility Name
CHU d'Angers
City
Angers
Country
France
Facility Name
Hôpital des Enfants - Pellegrin
City
Bordeaux
Country
France
Facility Name
CHRU Lille
City
Lille
Country
France
Facility Name
Hospices Civils de Lyon
City
Lyon
Country
France
Facility Name
Hôpital de la Timone
City
Marseille
Country
France
Facility Name
Hôpital Necker-Enfants malades
City
Paris
Country
France
Facility Name
Hôpital Robert-Debré
City
Paris
Country
France
Facility Name
CHU de Rennes
City
Rennes
Country
France
Facility Name
Hôpital de Hautepierre
City
Strasbourg
Country
France
Facility Name
CHU de Toulouse
City
Toulouse
Country
France
Facility Name
CHU de Tours
City
Tours
Country
France
Facility Name
Hôpital Brabois - Rue du Morvan
City
Vandoeuvre-les-Nancy
Country
France

12. IPD Sharing Statement

Learn more about this trial

Efficacy of Phosphatidylserine Enriched With n-3 PUFA Supplementation on ADHD in Children With Epilepsy

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