Efficacy and Safety Eval of Guanfacine Hydrochloride in Combination With Psychostimulants in Adults (18-65). (ADINT2012)

Double-Blind, Randomized, Placebo-Controlled, Single- Center, Dose Optimization Study Evaluating Efficacy and Safety of Guanfacine Hydrochloride in Combination With Psychostimulants in Adults Aged 18-65 Years With a Diagnosis of ADHD

This is considered an investigator-initiated clinical research trial, which means that your study doctor is researching a particular medication (in this case a medication that is currently FDA- approved) for the treatment of AD/HD in individuals ages 6-17. The medication is guanfacine hydrochloride.

The hypothesis is that this medication could be used in adults with Attention Deficit/Hyperactivity Disorder who have not received satisfactory results with their current stimulant ADHD medication. The study drug is investigational for use in adults. Investigational means it has not been approved by the U.S. Food and Drug Administration (FDA) for use in adults.

Study Overview

• Status: Completed
• Conditions: Adult Attention-Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: Guanfacine Hydrochloride; Other: Placebo

Detailed Description

The purpose of this study is to determine whether guanfacine hydrochloride used as an adjunct therapy (to subjects' current stimulant medication) would bring about a statistically significant improvement in AD/HD symptoms.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and females (non pregnant) ages 18-65
• Current diagnosis of ADHD and have met the DSM-IV-TR criteria for ADHD
• Currently taking an adequate dose stimulant to treat their ADHD (with a sub-optimal response). A suboptimal response is determined by a baseline score of 28 or greater on the ADHD-RS or a CGI score of 4 or greater.
• Subjects must be of normal intelligence
• English speaking
• Able to swallow pills.

Exclusion Criteria:

• Non pregnant or lactating females
• Severe Axis I and Axis II disorders
• Suicidal
• Tourette's
• Heart disease or any other serious chronic or acute unstable medical conditions/illnesses that would compromise participation or likely lead to hospitalization during the duration of the study.
• A known history or presence of cardiovascular, hepatic, renal, respiratory, or hematologic abnormalities, narrow angle glaucoma, or any other unstable medical or psychiatric conditions (as judged by the primary investigator)
• A current or recent history (within the past 6 months) of suspected substance abuse and/or drug dependence as defined by DSM-IV-TR criteria
• Healthy weight (not under or over as judged by investigator)
• No immediate family member of the investigator or research staff No involvement in a research study in the last 30 days.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Guanfacine Hydrochloride; mg Guanfacine Hydrochloride (orally, QD); mg Guanfacine Hydrochloride (orally, QD); mg Guanfacine Hydrochloride (orally, QD); mg Guanfacine Hydrochloride (orally, QD); mg Guanfacine Hydrochloride (orally, QD); mg Guanfacine Hydrochloride (orally, QD)	Drug: Guanfacine Hydrochloride; mg Guanfacine Hydrochloride (orally); mg Guanfacine Hydrochloride (orally); mg Guanfacine Hydrochloride (orally); mg Guanfacine Hydrochloride (orally); mg Guanfacine Hydrochloride (orally); mg Guanfacine Hydrochloride (orally); Other Names: Intuniv
Placebo Comparator: Sugar Pill; mg Placebo; mg Placebo; mg Placebo; mg Placebo; mg Placebo; mg Placebo	Other: Placebo; Placebo of matching mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADHD-RS Change From Baseline to Endpoint	The ADHD-RS is an 18-item scale based on DSM-IV criteria for ADHD. Each item is rated using a likert scale from 0 (none) to 3 (severe), with a total score range of 0-54, with higher scores indicating more symptoms/severity. In this study, we compared the mean change in ADHD-RS total score from baseline to endpoint of the study.	0 weeks, 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Clinical Global Impression (Severity)	The Clinical Global Impression- Severity (CGI-S) is a clinician-assessed likert scale used to determine the severity of a patient's presenting symptoms. The scale evaluates a subject's illness from 1 (normal, not at all ill) to 7 (extremely ill). The results reported below indicate the magnitude of change in terms of mean points on a scale for each study condition (IMP or Placebo).	0 weeks, 8 weeks
The Clinical Global Impression- Improvement (CGI-I)	The Clinical Global Impression-Improvement (CGI-I) is a clinician-assessed likert scale measuring change in presenting symptoms from previous visit. The CGI-I is a 7-item scale with with 1 indicating that the subject has very much improved and 7 indicating that the subject has become very much worse.	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue Symptoms Inventory (FSI) Change From Baseline to Endpoint	The FSI is a 14-item self-report measure designed to assess the severity, frequency, and daily pattern of fatigue as well as its perceived interference with quality of life. Severity is measured on separate 11-point scales (0=not at all fatigued; 10=as fatigued as I could be) that assess most, least, and average fatigue since last visit, as well as current fatigue. The minimum score would be 0, maximum score would be 140. Scores below reflect mean improvement in FSI score from baseline (visit 0) to endpoint (visit 8). The FSI was used to measure safety and tolerability of study drug.	0 weeks, 8 weeks
Hamilton Anxiety Inventory Change From Baseline to Endpoint	The Hamilton Anxiety Scale is a 14-items clinician-rated scale designed to measure anxiety severity. Each of the 14 items is scored from 0 (symptom not persent) to 4 (severe symptom). The total range is 0-56. A total score of less than 17 indicates mild severity, 18-24 indicates mild to moderate severity, and a score of 25-30 indicates moderate to severe symptoms. In this study, we compared the mean change in the Hamilton Anxiety scale from baseline to week 8 between guanfacine hyrdochloride and placebo-treated patients to assess safety and tolerability of study drug.	0 weeks, 8 weeks
Arizona Sexual Experiences Scale (ASEX) Change From Baseline to Endpoint	The Arizona Sexual Experiences Scale (ASEX) is both a self-administered or clinician-administered questionnaire. It is a user-friendly 5-item rating scale. The ASEX utilizes short, easy to understand, and less intrusive questions that explores the follwoing aspects of sexuality: sex drive; arousal 3a. penile erection 3b. vaginal lubrication 4. ability to reach orgasm 5. satisfaction from orgasm Scores can range from a minimum of 6 (indicating minimal problems with sexual functioning) to 36 (indicating maximum problems with sexual functioning). Mean change from baseline (visit 0) to endpoint (visit 8) are presented below. The ASEX was used to assess safety and tolerability of drug from baseline to endpoint	0 weeks, 8 weeks
Hamilton Depression Rating Scale (HAM-D) Change From Baseline to Endpoint	The HAM-D is a clinician administered multiple item scale used to provide an indication of depression symptom severity. It is designed for adults. Each item on the questionnaire is scored on a 3 or 5 point scale. The HAM-D is comprised of 21 items, however, the total score is based on the sum of the scores from the first 17 items. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. Thus the possible total score range is 0 (minimum) to 40 (maximum) with a higher score indicating greater severity of depression. Accordingly, a low HAM-D score would indicate a better outcome. Mean change scores from baseline (visit 0) to endpoint (visit 8) are presented below.	0 weeks, 8 weeks
The Pittsburgh Sleep Quality Index (PSQI) Change From Baseline to Endpoint	The Pittsburgh Sleep Quality Index (PSQI) is an effective instrument used to measure the quality and patterns of sleep in adults. It differentiates "poor" from "good" sleep by measuring seven domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. The individual self rates each of these seven areas of sleep. Scoring of the answers is based on a 0 to 3 scale, whereby 3 reflects the negative extreme on the Likert Scale. Total score range is from 0 to 21. The mean improvement from baseline (visit 0) to endpoint (visit 8) are presented below. PSQI was used to assess safety and tolerability of study drug.	0 weeks, 8 weeks

Collaborators and Investigators

• Sponsor: Rochester Center for Behavioral Medicine
• Collaborators: Shire
• Investigators: Principal Investigator: Joel L Young, MD, Rochester Center for Behavioral Medicine

Publications and helpful links

General Publications

• Butterfield ME, Saal J, Young B, Young JL. Supplementary guanfacine hydrochloride as a treatment of attention deficit hyperactivity disorder in adults: A double blind, placebo-controlled study. Psychiatry Res. 2016 Feb 28;236:136-141. doi: 10.1016/j.psychres.2015.12.017. Epub 2015 Dec 17.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: November 20, 2013
• First Submitted That Met QC Criteria: May 14, 2014
• First Posted (Estimated): May 19, 2014

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: July 25, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Antihypertensive Agents; Guanfacine
• Other Study ID Numbers: 1129704 ADINT