Recruiting

Methylphenidate vs. Guanfacine

Sponsor:

Children's Hospital Medical Center, Cincinnati

Code:

NCT07300956

Conditions

Attention-Deficit/Hyperactivity Disorder (ADHD)

Eligibility Criteria

Sex: All

Age: 3 - 5

Healthy Volunteers: Not accepted

Interventions

Guanfacine (GUA)

Methylphenidate (MPH)

Study Details

Brief summary:

This project will evaluate the effectiveness of Methylphenidate versus Guanfacine in treating Attention-Deficit/Hyperactivity Disorder (ADHD) in children aged 3 through 5 years (inclusive), as measured by clinician rating of global improvement.

Conditions

Attention-Deficit/Hyperactivity Disorder (ADHD)

Study ID

NCT07300956

Start date

Feb 16, 2026

Status verified date

Apr, 2026

Completion date

Jul, 2030

Anticipated

Primary completion date

Feb, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 3 - 5

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. Males or females 3 to 5 years of age, inclusive (e.g. children age 5 years, 11 months are eligible).
2. Child has a confirmed diagnosis of moderate or severe Attention-Deficit/Hyperactivity Disorder (diagnostic code: F90.9) based on Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-5) criteria, review of supportive evidence (caregiver interview, behavioral observations, Vanderbilt Attention-Deficit/Hyperactivity Disorder Rating Scale results, any school or daycare information provided by caregiver).
3. Clinician-rated Clinical Global Impairment-Severity (see description below) rating of ≥4 (denoting moderate or greater impairment due to their Attention-Deficit/Hyperactivity Disorder symptoms).
4. The child's clinician and caretakers have decided on or are considering initiating drug therapy (with either Methylphenidate or Guanfacine).
5. Primary language is English or Spanish.

Exclusion Criteria:

1. History of taking Methylphenidate or Guanfacine. Prior use of other Attention-Deficit/Hyperactivity Disorder medications or other psychotropic medications is allowed.
2. Current use of other Attention-Deficit/Hyperactivity Disorder medications (e.g., amphetamines), other psychotropic medications (e.g., atypical antipsychotics or serotonin reuptake inhibitors), or centrally active depressants (such as phenothiazines, barbiturates, or benzodiazepines)
3. Electronic Health Record documentation of moderate to severe global developmental delay (F88) or intellectual disability (F70), or a score of <55 on the Vineland Adaptive Behavior Scales-3.
4. Medical contraindications to taking Methylphenidate or Guanfacine, including cardiac risk factors (e.g. known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease), increased intraocular pressure, glaucoma, verbal tics, Tourette's Syndrome, psychosis

Study Design

Enrollment

370 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Guanfacine

After engaging in behavioral therapy, participants randomized to this group will be prescribed Guanfacine. The child's prescribing clinician will determine the form and dose of Guanfacine that the child receives.

active comparator: Methylphenidate

After engaging in behavioral therapy, participants randomized to this group will be prescribed Methylphenidate. The child's prescribing clinician will determine the form and dose of Methylphenidate that the child receives.

Interventions

Guanfacine (GUA)

After engaging in behavioral therapy, participants randomized into this group participants will be prescribed Guanfacine. Each child's prescribing clinician determines the form and dose of guanfacine that the child receives.

Guanfacine (GUA) medication brand names include: Intuniv, Tenex, guanfacine hydrochloride- extended release, guanfacine hydrochloride- immediate release

Methylphenidate (MPH)

Participants randomized into this group will be prescribed Methylphenidate. Each child's prescribing clinician determines the form and dose of methylphenidate that the child receives.

Methylphenidate (MPH) medication brand names include: Adhansia XR, Aptensio XR, Azstarys, Concerta, Cotempla XR-ODT, Daytrana, Focalin, Focalin XR, Jornay PM. Metadate CD, Methylin (liquid), Relexxii, Ritalin, Ritalin LA, Quillichew ER, Quillivant XR (liquid), methylphenidate hydrochloride- extended release, methylphenidate hydrochloride- immediate release

Primary outcome measure

  • Clinical Global Impression-Improvement [ Time Frame: From enrollment to the end of the 16-week medication treatment. ]

Central Contacts and Locations

Central contacts

Locations

Stanford Medicine Children's Health

Recruiting

Palo Alto, California, United States, 94304

Contacts

Melisa Deras, MS

mderas08@stanford.edu

Principal Investigator:

Irene Loe, MD

Boston Children's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Principal Investigator:

Elizabeth Harstad, MD

Children's Mercy Hospital

Recruiting

Kansas City, Missouri, United States, 64108

Contacts

Luis Saniz Y Diaz, BBA

lesainzydiaz@cmh.edu

Principal Investigator:

Simone Moody, PhD

Cincinnati Children's Hospital Medical Center

Recruiting

Cincinnati, Ohio, United States, 45229

Contacts

Hannah R Bush, MA

Hannah.Bush@cchmc.org

Principal Investigator:

Tanya E Froehlich, MD

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Jessica Meline, MPH

melinej@chop.edu

Principal Investigator:

Nathan Blum, MD

More Information

Sponsor

Children's Hospital Medical Center, Cincinnati

Last update posted

Sep 14, 2026

Last verified

Apr, 2026

Keywords

  • Attention-Deficit/Hyperactivity Disorder
  • Methylphenidate
  • Guanfacine
  • Preschool Children
  • Comparative Effectiveness
  • Prospective Study

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-15. This information was provided to ClinicalTrials.gov by Children's Hospital Medical Center, Cincinnati on 2026-09-14.