Guanfacine Extended Release and Mindfulness Skills Therapy

NCT ID: NCT03258476

Last Updated: 2021-03-08

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-01
• Study Completion Date: 2019-12-03

Brief Summary

Teenagers are invited to take part voluntarily in a research study of a study drug known as guanfacine extended release (Intuniv™) and a type of psychotherapy called Mindfulness Skills Training which teaches people how to focus on the present moment in a nonjudgmental manner to help them cope with their stresses and worries. Teenagers are being asked to take part in this study if they have had traumatic stress related over arousal symptoms. He/she may also have difficulties with worries, anxiety, temper, aggression, quick mood changes, behavior problems, and/or difficulties with symptoms of Attention Deficit Hyperactivity Disorder (ADHD) including inattention, hyperactivity, and impulsivity with or without Posttraumatic Stress Disorder (PTSD); and is not responding adequately to his/her current treatment.

The primary purpose of the teenager's participation in this study is to help answer the following research question(s), and not to provide treatment for his or her condition:

• To investigate if Intuniv™ helps for the symptoms of traumatic stress and emotional and behavioral overarousal in children with a history of traumatic developmental stress with and without PTSD.
• To investigate if Intuniv™ helps your teenager engage with and benefit from Mindfulness Skills Training therapy
• To better understand how Intuniv™ works in the brain.
• To investigate how well your child tolerates Intuniv™ during the study.

Conditions

Stress Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GXR and Mindfulness Skills

Guanfacine Extended Release (GXR) will be started at 1 mg/day at Week 1 and tapered up by 1 mg per week to a maximum dose of 7 mg/day by week 7 (maximum of 6 weeks on drug). GXR dosing will be flexible for the first 5 weeks of the study based upon patient response and tolerability to drug. Optimal dose will be defined as that necessary to achieve ≥ 30% reduction in symptoms and a CGI-Improvement Score ≤ 2. Upon re-evaluation at (T1) and entry into the psychotherapy protocol dosing will become fixed for the remainder of the study. Mindfulness Skills Therapy will occur for the next 10 weeks.

Group Type: EXPERIMENTAL

Guanfacine Extended Release

Intervention Type: DRUG

Intuniv (guanfacine) is a prescription medicine used to treat attention deficit hyperactivity disorder (ADHD) in children who are at least 6 years old. An open-label trail of guanfacine extended release (GXR 1-4 mg/daily; Intuniv™) suggested benefits in improving behavioral and emotional regulation in children and adolescents with symptoms of traumatic stress. However, to date no controlled clinical trial has been completed assessing the effects of GXR on traumatic stress symptoms in youths

Mindfulness Skills Therapy

Intervention Type: BEHAVIORAL

Mindfulness is a therapy for anxiety and stress. Mindfulness forms of therapy involve regulation of attention, maintaining it in immediate experience, regardless of the valence and desirability of the experience. To reduce anxiety, Mindfulness encourages observing and accepting anxiety-related thoughts

Placebo and Mindfulness Skills

Placebo will be started at "1 mg/day" at Week 1 and tapered up by "1 mg" per week to a maximum dose of "7 mg/day" by week 7 (maximum of 6 weeks on drug). Placebo dosing will be flexible for the first 5 weeks of the study based upon patient response. Optimal dose will be defined as that necessary to achieve ≥ 30% reduction in symptoms and a CGI-Improvement Score ≤ 2. Upon re-evaluation at (T1) and entry into the psychotherapy protocol dosing will become fixed for the remainder of the study. Mindfulness Skills Therapy will occur for the next 10 weeks.

Group Type: ACTIVE_COMPARATOR

Mindfulness Skills Therapy

Intervention Type: BEHAVIORAL

Mindfulness is a therapy for anxiety and stress. Mindfulness forms of therapy involve regulation of attention, maintaining it in immediate experience, regardless of the valence and desirability of the experience. To reduce anxiety, Mindfulness encourages observing and accepting anxiety-related thoughts

Placebo

Intervention Type: DRUG

Placebo oral capsule

Interventions

Guanfacine Extended Release

Intuniv (guanfacine) is a prescription medicine used to treat attention deficit hyperactivity disorder (ADHD) in children who are at least 6 years old. An open-label trail of guanfacine extended release (GXR 1-4 mg/daily; Intuniv™) suggested benefits in improving behavioral and emotional regulation in children and adolescents with symptoms of traumatic stress. However, to date no controlled clinical trial has been completed assessing the effects of GXR on traumatic stress symptoms in youths

Intervention Type: DRUG

Mindfulness Skills Therapy

Mindfulness is a therapy for anxiety and stress. Mindfulness forms of therapy involve regulation of attention, maintaining it in immediate experience, regardless of the valence and desirability of the experience. To reduce anxiety, Mindfulness encourages observing and accepting anxiety-related thoughts

Intervention Type: BEHAVIORAL

Placebo

Placebo oral capsule

Intervention Type: DRUG

Other Intervention Names

Intuniv

Eligibility Criteria

Inclusion Criteria

• A lifetime history of traumatic stress documented by self and/or caregiver response on the youth self-report and or caregiver-report Structured Trauma-Related Experiences & Symptoms Screener (STRESS) (i.e., at least one yes response on STRESS items 1-25). AND
• A baseline STRESS total score ≥ 21 for females or a baseline STRESS total score ≥ 17 for males (STRESS items # 26-48: range of total scores: 0-69) 68 as completed by caregiver OR youth.

AND/OR

• A lifetime history of traumatic stress documented by self and/or caregiver response on the youth self-report and or caregiver-report Structured Trauma-Related Experiences & Symptoms Screener (STRESS) (i.e., at least one yes response on STRESS items 1-25). AND
• Clinically significant aggressive behavior during the preceding week assessed by a caregiver-completed Retrospective Modified Overt Aggression (R-MOAS ≥ 24).73 AND
• A baseline Clinical Global Impressions-Severity Score ≥ 4.74
• Assent of child and consent of both parents/caregivers.
• Living with a caregiver legally empowered to permit study enrollment and able to complete protocol assessments.
• English speaking
• The child is not responding to or is not tolerating well their current treatment as reported by the parent or child.
• If female and reports that she is sexually active: Is willing to take a pregnancy test before study participation AND is willing to take an additional pregnancy test during the study as appropriate and necessary, and as determined by the Medical Director of the study.
• Child and parent willing to give permission for the study team to contact the child's primary care physician, mental health clinician and /or mental health prescriber to communicate any changes in child's symptom status or medications as a result of participation in this research.

Exclusion Criteria

:• A history of cardiovascular disease, previous history of ECG abnormalities, syncope, exercise-induced cardiovascular symptoms, or any other unstable medical illness/allergy (i.e., seizure disorder) that in the opinion of the site Medical Director precludes enrollment in the study. A clinically significant history of Raynaud's disease is exclusionary.

• Autistic disorder, persons with intellectual disability (IQ ≤ 70), clinically significant (in the judgment of the site Medical Director) substance abuse disorder (within the past 30 days), bipolar I disorder, schizophrenia or other psychotic disorder, or major depressive disorder with symptoms that are severe enough (e.g. suicidality) that in the opinion of the site Medical Director excludes study participation.
• Concomitant Medications: Use of other psychiatric medications including extended release guanfacine (study drug) besides a stable dose of stimulants or atomoxetine for ADHD for the study duration is exclusionary for this protocol. All other medications will undergo discontinuation.
• Patients who are unable to comply with the study protocol.
• Females of childbearing age that are sexually active and not receiving a medically acceptable form of birth control and/or active pregnancy.
• Already taking Guanfacine Extended Release

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

UConn Health

OTHER

Sponsor Role: lead

Responsible Party

Asima Zehgeer

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Asima F Zehgeer, MD

Role: PRINCIPAL_INVESTIGATOR

UConn Health

Locations

UConn Health

Farmington, Connecticut, United States

Countries

United States

Other Identifiers

17-080-2

Identifier Type: -

Identifier Source: org_study_id