ADHDPhase 3PADNCT01340690
Efficacy Study of Polyunsaturated Fatty Acids in Children and Adolescents With Attention Deficit/ Hyperactivity Disorder
A Phase 3 study testing ω-3 fatty acids suspension in people with ADHD, run by Johannes Gutenberg University Mainz at 5 sites in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- ADHD
- What is being tested?
- ω-3 fatty acids suspension
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 284 participants
- Where
- 5 sitesGermany
- Study dates
- 8 Mar 2011to 1 Mar 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites
DRK Fachklinik für Kinder- und Jugendpsychiatrie, Psychotherapie, Psychosomatik
Bad Neuenahr, D 53474
Charité - Universitätsmedizin Berlin, CVK Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters
Berlin, D 13353
University Medicine Mainz
Mainz, D 55131
Kinderzentrum Maulbronn gGmbH
Maulbronn, D 75433
Johanniter - Zentrum für Kinder- und Jugendpsychiatrie Neuwied
Neuwied, D 56564
About this study
Official title: 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)
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).
Read the 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.
- Conditions
- ADHD
- Being tested
- ω-3 fatty acids suspension, placebo suspension
- Keywords
- ADHD, children, adolescents, Polyunsaturated Fatty Acids, ADHDRS - IV
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ω-3 fatty acids suspensionDietary supplement
Also called Esprico(R) suspension, 2 verum to 1 placebo
2 bags of Esprico(R) suspension given orally once daily in the morning for 84 days
placebo suspensionDietary supplement
suspension to mimic verum Esprico (R) suspension. 2 bags of Esprico(R) placebo suspension given orally once daily in the morning for 84 days
| Study group | Role | What they receive |
|---|---|---|
| ω-3 fatty acids suspension | Active comparator | 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) Receives: Dietary Supplement: ω-3 fatty acids suspension |
| placebo suspension | Placebo comparator | 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. Receives: Dietary Supplement: placebo suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Difference in total score between baseline and end of study, an expected average of 84 days
Secondary outcomes (6)
Barkley´s Side Effects Rating Scale
Number of Participants with Adverse Events.
Measured: Baseline and each visit, monthly, an expected average of 84 days in total
Montgomery-Åsberg-Depression Rating Scale (MADRS)
Assessment of Symptoms of Depression.
Measured: Baseline and each visit, monthly, an expected average of 84 days in total
Continuous Performance Test (CPT)
Differences in Continuous Performance Test.
Measured: change from Baseline to end of treatment, an expected average of 84 days
Nutrition protocol
Assessment of diet habits.
Measured: 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.
Measured: 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,...
Measured: change from Baseline to end of treatment, an expected average of 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2011 (estimated)
- Study start8 Mar 2011
- Primary completion31 Mar 2016
- Study completion1 Mar 2017
Why it stopped: The sample size of the planned interims analysis was achieved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ADHDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 284 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johannes Gutenberg University Mainz
- Sponsor type
- University, hospital or other
- Collaborators
- Engelhard Arzneimittel GmbH & Co.KG
- Responsible party
- Principal investigator, Prof. Huss, Johannes Gutenberg University Mainz
- Investigators
- Michael Huss, Prof. Dr., Principal investigator, University Medicine, Mainz, Dep. of Child and Adolescent Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01340690
- Sponsor's protocol ID
- PAD-EA-10-01-067
- Acronym
- PAD
- Status last verified
- Sep 2017
- First submitted
- 7 Apr 2011
- Last updated
- 20 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Schuchardt JP, Huss M, Stauss-Grabo M, Hahn A. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr. 2010 Feb;169(2):149-64. doi: 10.1007/s00431-009-1035-8. Epub 2009 Aug 12.
PubMed 19672626Huss M, Volp A, Stauss-Grabo M. Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit/hyperactivity problems - an observational cohort study. Lipids Health Dis. 2010 Sep 24;9:105. doi: 10.1186/1476-511X-9-105.
PubMed 20868469
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01340690
- Acronym / sponsor ID
- PAD / PAD-EA-10-01-067
- Conditions
- ADHD
- Keywords
- ADHD, children, adolescents, Polyunsaturated Fatty Acids, ADHDRS - IV
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sample size of the planned interims analysis was achieved
- Enrolment
- 284 participants (actual)
- Lead sponsor
- Johannes Gutenberg University MainzUniversity, hospital or other
- Collaborators
- Engelhard Arzneimittel GmbH & Co.KG
- Study start
- 8 Mar 2011 (actual)
- Primary completion
- 31 Mar 2016 (actual)
- Study completion
- 1 Mar 2017 (actual)
- First posted
- 22 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| ω-3 fatty acids suspension | Active comparator | Dietary Supplement: ω-3 fatty acids suspension2 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) |
| placebo suspension | Placebo comparator | Dietary Supplement: placebo suspension2 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. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ω-3 fatty acids suspensionAlso: Esprico(R) suspension, 2 verum to 1 placebo2 bags of Esprico(R) suspension given orally once daily in the morning for 84 days | Dietary supplement | ω-3 fatty acids suspension |
| placebo suspensionsuspension to mimic verum Esprico (R) suspension. 2 bags of Esprico(R) placebo suspension given orally once daily in the morning for 84 days | Dietary supplement | placebo suspension |
Primary outcome
ADHDRS - IV
Time frame: 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.
6 secondary outcomes
Barkley´s Side Effects Rating Scale
Time frame: Baseline and each visit, monthly, an expected average of 84 days in total
Montgomery-Åsberg-Depression Rating Scale (MADRS)
Time frame: Baseline and each visit, monthly, an expected average of 84 days in total
Continuous Performance Test (CPT)
Time frame: change from Baseline to end of treatment, an expected average of 84 days
Nutrition protocol
Time frame: baseline
Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P)
Time frame: change from Baseline to end of treatment, an expected average of 84 days
PUFA associated blood parameters
Time frame: change from Baseline to end of treatment, an expected average of 84 days
Results and safety
The study was stopped early (reason given: The sample size of the planned interims analysis was achieved). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2017.
- Background: PubMed 19672626Schuchardt JP, Huss M, Stauss-Grabo M, Hahn A. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr. 2010 Feb;169(2):149-64. doi: 10.1007/s00431-009-1035-8. Epub 2009 Aug 12.
- Background: PubMed 20868469Huss M, Volp A, Stauss-Grabo M. Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit/hyperactivity problems - an observational cohort study. Lipids Health Dis. 2010 Sep 24;9:105. doi: 10.1186/1476-511X-9-105.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Huss, Prof. Dr. principal investigator
University Medicine, Mainz, Dep. of Child and Adolescent Psychiatry
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ω-3 fatty acids suspension in people with ADHD, run by Johannes Gutenberg University Mainz at 5 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The sample size of the planned interims analysis was achieved). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ADHDRS - IV (time frame: Difference in total score between baseline and end of study, an expected average of 84 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01340690, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2017.