Efficacy Study of Polyunsaturated Fatty Acids in Children and Adolescents With Attention Deficit/ Hyperactivity Disorder

Study Overview
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Brief Summary
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This study will determine the nutritional efficacy of Polyunsaturated Fatty Acids (PUFAs) in combination with zinc and magnesium, in children and adolescents diagnosed with Attention Deficit/ Hyperactivity Disorder (ADHD). The nutritional efficacy has to be proven in agreement with the German Verordnung über Diätetische Lebensmittel (DiätV) and the corresponding European Directive 1999/21/EC. This objective is reached by performing a placebo-controlled supplementation study with a main efficacy criterion which is also being used in pivotal studies of stimulant and non-stimulant drugs, i.e. the treatment differences between final visit and baseline in the Attention Deficit Hyperactivity Disorder Rating Scale, Parent Version IV (ADHDRS-IV).

Detailed Description
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The syndrome of ADHD affects 5-6% of the children and adolescents worldwide. The hallmarks are inattention, impulsivity and hyperactivity. Due to parent's fear of significant adverse effects caused by stimulant or non-stimulant therapy a high degree of children with ADHD remains untreated. Recent observational studies showed that ADHD is often associated with decreased nutritional status of certain PUFAs, zinc and magnesium which might be due to metabolic disturbances in the case of fatty acids. First interventional studies revealed that a supplementation of these nutrients may affect ADHD-related disorders and might improve certain clinical parameters, such as concentration. Participants will be randomly assigned to receive either a nutritional supplement or placebo once a day for the duration of 84 days. Participants will come in for the assessment of ADHD symptoms, compliance and the assessment of secondary outcome variables. Side effects will be monitored continuously and also assessed by rating scales.

Official Title
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PAD-study: Nutritional Efficacy of Polyunsaturated Fatty Acids (Omega-3 and Omega-6) in Combination With Zinc and Magnesium Versus Placebo in Children and Adolescents With Attention Deficit/ Hyperactivity Disorder (ADHD)

Conditions
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ADHD

Intervention / Treatment
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* Dietary Supplement: ω-3 fatty acids suspension
* Dietary Supplement: placebo suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written Informed Consent by parents and patients (separately for age groups 6 - 11 years and 12 - 17 years) Children and adolescents of both gender in the age group between 6 and 17 years Confirmed diagnosis of ADHD by semi-structured clinical interview Kiddie Schedule for Affective Disorders and Schizophrenia for school-age children (K-SADS) ADHDRS-IV-Parent Version (18-Item-Scale): Investigator Administered and Scored ≥24 Sufficient knowledge of the German language Exclusion Criteria: Known hypersensitivity against components of either the verum or placebo food All serious internal diseases All severe psychiatric diseases except oppositional defiant disorders Current intake of the following medication: antidepressants and other psychotropic medication Recent intake of ω-3 fatty acids supplementation Indication for hospitalization Suicidality (including suicidal thoughts) intelligence quotient < 70 Previous medication with stimulants within 4 weeks Placement in an institution on official or judicial ruling Lack of willingness to store and transmit pseudonym data according to German regulations Parallel participation in another trial, or less than 4 weeks ago Patients foreseeable requiring a primary medication with methylphenidate during the study period of 12 weeks

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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
Interventional Model Description: We use the dietary supplementation like a medication and performed the study like a phase 3 medication study, because the dietary supplementation (verum) is available as special preparation in drug stores.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ω-3 fatty acids suspension<br>2 bags of Esprico(R) suspension each day. Each 4ml suspension bag includes 400mg eicosapentaenoic acid (EPA), 40mg docosahexaenoic acid (DHA), 5.4 mg gamma-linolenic acid (GLA), 80 mg magnesium, 5 mg zinc and consists of linseed oil, xylitol, sea fish oil with high portion of omega-3-acids, magnesium citrate, vegetable oil, orange flavour, evening primrose oil, zink gluconate, soya lecithin, citric acid, acesulfame k (E950) | Dietary Supplement: ω-3 fatty acids suspension<br>* 2 bags of Esprico(R) suspension given orally once daily in the morning for 84 days<br>* Other names: 2 verum to 1 placebo;|
| Placebo Comparator: placebo suspension<br>2 bags of Esprico (R) placebo suspension. Includes no ω-3 fatty acids, no ω-6 fatty acids, no magnesium and no zinc, but other vegetable oils, orange flavor, etc. | Dietary Supplement: placebo suspension<br>* suspension to mimic verum Esprico (R) suspension. 2 bags of Esprico(R) placebo suspension given orally once daily in the morning for 84 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADHDRS - IV | The primary outcome measure for efficacy will be the absolute change in the ADHDRS total score between baseline and day 84 of randomized treatment. | Difference in total score between baseline and end of study, an expected average of 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Barkley´s Side Effects Rating Scale | Number of Participants with Adverse Events. | Baseline and each visit, monthly, an expected average of 84 days in total | 
| Montgomery-Åsberg-Depression Rating Scale (MADRS) | Assessment of Symptoms of Depression. | Baseline and each visit, monthly, an expected average of 84 days in total | 
| Continuous Performance Test (CPT) | Differences in Continuous Performance Test. | change from Baseline to end of treatment, an expected average of 84 days | 
| Nutrition protocol | Assessment of diet habits. | baseline | 
| Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) | Assessment of Symptoms of ADHD and to what degree individual's behavior or emotional problems have impacted various clinically relevant domains of functioning. | change from Baseline to end of treatment, an expected average of 84 days | 
| PUFA associated blood parameters | complete fatty acid profile in red blood cells and relevant ratios, e.g. Omega-HS-Index, Plasma-Zinc, Plasma-Copper, Serum-Magnesium, Serum-Ferritin,... | change from Baseline to end of treatment, an expected average of 84 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, children, adolescents, Polyunsaturated Fatty Acids, ADHDRS - IV