Effect of Pycnogenol® on ADHD

Study Overview
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Brief Summary
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This double blind, randomised controlled trial examines the effect of a commercially available nutritional supplement on behaviour of ADHD patients, as well as on their physical and psychiatric co-morbidities, and level of oxidative stress and immune activity, as compared to placebo and standard pharmaceutical treatment for ADHD.

Official Title
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Effect of a Polyphenol-rich Plant Extract on Attention-Deficit Hyperactivity Disorder (ADHD): A Randomized, Double Blind, Placebo and Active Product Controlled Multicenter Trial.

Conditions
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ADHD

Intervention / Treatment
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* Dietary Supplement: Pycnogenol
* Drug: Methylphenidate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is between 6-12 years old (both inclusive). The patient satisfies the DSM-IV criteria for ADHD or ADD. The patient has a responsible caregiver who is able to provide information about the patient's functional status. Written informed consent is obtained from the patient and the legally accepted representative. Exclusion Criteria: The patient does satisfy the DSM-IV for autism spectrum disorder. The patient does have situational hyperactivity, pervasive developmental disorders, schizophrenia, other psychotic disorders such as mood or anxiety disorder, personality disorder as unsocial behaviour, personality change due to a general medical condition, mental retardation (IQ < 70), understimulating environments, conduct disorder, chorea and other dyskinesias. The patient does not have tics or Tourette's syndrome, or personal or family history of psychotic disorder, bipolar illness, depression, or suicide attempt. The patient does have any chronic medical disorder (diabetes, epilepsy or other seizure disorder, autoimmune disorder, gastrointestinal disorder, renal or cardiovascular disorders, etc.) or acute inflammatory disease. The patient does not have glaucoma, heart disease, heart rhythm disorder, high blood pressure, or peripheral vascular disease such as Raynaud's syndrome. The patient did use any of these medications during the 3 months before entering the study: clonidine, guanethidine, blood thinners (e.g. warfarin or Coumadin), antidepressants (e.g. amitriptyline, citalopram, doxepin, fluoxetine, nortriptyline, paroxetine, sertraline), cold or allergy medicine that contains a decongestant, medications to treat high or low blood pressure, seizure medicine (e.g. phenobarbital, phenytoin, primidone), or diet pills. The patient did take MAO inhibitor (isocarboxazid, linezolid, phenelzine, rasagiline, selegiline or tranylcypromine) in the past 14 days. The patient has any other contraindication for the use of methylphenidate. The patient did use vitamin/mineral/herbal/omega-3 supplements or other any medication (psychoactive medication, antibiotics, anti-inflammatory drugs, melatonin, etc.) > 1 week during the 3 months before inclusion.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pycnogenol<br>Dietary supplement, standardised extract of French maritime Pine bark. This group receives a nutritional supplement for a period of 10 weeks. Subjects < 30 kg body weight: 20 mg Pycnogenol/day Subjects >= 30 kg body weight: 40 mg Pycnogenol/day | Dietary Supplement: Pycnogenol<br>* Dietary supplement, standardised extract of French maritime Pine bark. This group receives a nutritional supplement for a period of 10 weeks.<br>|
| Placebo Comparator: Placebo<br>Placebo treatment (identical capsules containing excipients only) | Other: Placebo<br>* Placebo treatment (identical capsules containing excipients only)<br>|
| Active Comparator: Methylphenidate<br>Standard pharmaceutical treatment for ADHD, slow release. Subjects < 30 kg body weight: 20 mg methylphenidate once per day Subjects >= 30 kg body weight: 30 mg methylphenidate once per day | Drug: Methylphenidate<br>* Standard pharmaceutical treatment for ADHD, slow release.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summed ADHD score of the ADHD-Rating Scale as rated by teachers |  | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summed ADHD score of the ADHD-Rating Scale as rated by teachers |  | 5 weeks | 
| Summed ADHD score of the ADHD-Rating Scale as rated by parents |  | 5 weeks, 10 weeks | 
| Summed ADHD score of the Social-Emotional Questionnaire (SEQ) as rated by parents and teachers |  | 10 weeks | 
| Scores on ADHD subscales of the ADHD-RS as rated by parents and teachers - hyperactivity, impulsivity and inattention |  | 5 & 10 weeks | 
| Scores on ADHD subscales of the SEQ as rated by parents and teachers - hyperactivity, impulsivity and inattention |  | 5 & 10 weeks | 
| Percentage of responders (ADHD-RS) as rated by parents and teachers | Score reduction of at least 20% for parents and/or teachers | 5 & 10 weeks | 
| Percentage of responders (SEQ) as rated by parents and teachers | Score reduction of at least 20% for parents and/or teachers | 5 & 10 weeks | 
| Social behavior problems subscale of the SEQ, as rated by parents and teachers |  | 10 weeks | 
| Anxiety subscale of the SEQ, as rated by parents and teachers |  | 10 weeks | 
| Physical and sleep complaints score as measured by the Physical Complaints Questionnaire (PCQ) |  | 5 & 10 weeks | 
| Erythrocyte glutathione (GSH) level |  | 10 weeks | 
| Urinary 8-OHdG level |  | 10 weeks | 
| Plasma cytokine levels |  | 10 weeks | 
| Plasma antibody levels |  | 10 weeks | 
| Gene expression |  | 10 weeks | 
| Serum neuropeptide Y |  | 10 weeks | 
| Serum zinc |  | 10 weeks | 
| Intestinal microbial composition |  | 10 weeks | 
| Intervention acceptability | Percentage of participants with side effects, treatment adherence and proportion of drop-outs | 10 weeks | 
| Intervention acceptability | Percentage of participants with side effects | 10 weeks | 
| Intervention acceptability | Proportion of drop-outs | 10 weeks | 
| Intervention acceptability | Treatment adherence | 10 weeks | 
| Urinary catecholamines |  | 10 weeks | 
| Plasma lipid-soluble vitamins |  | 10 weeks | 
| Long-term follow up | Long-term follow up on eventual treatment choice (medication, no intervention, nutritional supplement) | 6 months | 
| Long-term follow up | Long-term follow up on behaviour | 6 months | 
| Long-term follow up | Long-term follow up on physical/psychiatric complaints | 6 months |