Effect of Pycnogenol® on ADHD

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

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.

Study Overview

• Status: Completed
• Conditions: ADHD
• Intervention / Treatment: Dietary supplement: Pycnogenol; Other: Placebo; Drug: Methylphenidate

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Borgerhout, Belgium
    • Universitaire Kinder- en Jeugdpsychiatrie
  • Edegem, Belgium, 2650
    • University Hospital Antwerp
  • Ghent, Belgium, 9000
    • University Hospital Ghent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pycnogenol; 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; Dietary supplement, standardised extract of French maritime Pine bark. This group receives a nutritional supplement for a period of 10 weeks.
Placebo Comparator: Placebo; Placebo treatment (identical capsules containing excipients only)	Other: Placebo; Placebo treatment (identical capsules containing excipients only)
Active Comparator: Methylphenidate; 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; Standard pharmaceutical treatment for ADHD, slow release.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Nina Hermans
• Investigators: Study Director: Nina Hermans, PhD, Universiteit Antwerpen

Publications and helpful links

General Publications

• Verlaet AA, Ceulemans B, Verhelst H, Van West D, De Bruyne T, Pieters L, Savelkoul HF, Hermans N. Effect of Pycnogenol(R) on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial. Trials. 2017 Mar 28;18(1):145. doi: 10.1186/s13063-017-1879-6.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): November 20, 2020
• Study Completion (Actual): November 20, 2020

Study Registration Dates

• First Submitted: January 18, 2016
• First Submitted That Met QC Criteria: March 4, 2016
• First Posted (Estimate): March 7, 2016

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Immunologic Factors; Protective Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Adjuvants, Immunologic; Dopamine Uptake Inhibitors; Antioxidants; Central Nervous System Stimulants; Methylphenidate; Pycnogenols
• Other Study ID Numbers: Pycno 2015-14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No