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

Phase 3

Terminated

• Conditions: ADHD
• Interventions: Dietary Supplement: placebo suspension; Dietary Supplement: ω-3 fatty acids suspension

• Registration Number: NCT01340690
• Lead Sponsor: Johannes Gutenberg University Mainz

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-03-08
• Study First Submitted: 2011-04-07
• Study First Submitted QC: 2011-04-21
• Study First Posted: 2011-04-22
• Primary Completion: 2016-03-31
• Study Completion: 2017-03-01
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-19
• Last Update Posted: 2017-09-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 284

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo suspension	placebo suspension	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.
ω-3 fatty acids suspension	ω-3 fatty acids suspension	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)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Charité - Universitätsmedizin Berlin, CVK Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters; 🇩🇪 Berlin, Germany

DRK Fachklinik für Kinder- und Jugendpsychiatrie, Psychotherapie, Psychosomatik; 🇩🇪 Bad Neuenahr, Germany

Kinderzentrum Maulbronn gGmbH; 🇩🇪 Maulbronn, Germany

University Medicine Mainz; 🇩🇪 Mainz, Germany

Johanniter - Zentrum für Kinder- und Jugendpsychiatrie Neuwied; 🇩🇪 Neuwied, Germany