Clinical trial NCT03258476: Guanfacine Extended Release and Mindfulness Skills Therapy
Official title: Guanfacine Extended Release and Mindfulness in Traumatically Stressed Children and Adolescents Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Stress Disorder
Lead sponsor: UConn Health
Sponsor class: OTHER
Collaborators: name: Shire
name: Yale University
First posted: 2017-08-23
Enrollment: 0
Sex: ALL
Minimum age (years): 10
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The proposed study has two parts: (1) a randomized, double-blind controlled clinical trial of GXR vs. placebo for up to 7 weeks followed by, (2) 10 weeks of either GXR and Mindfulness psychotherapy (as a group or individual) or placebo and Mindfulness psychotherapy (as a group or individual).
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Changes in the Structured Trauma-Related Experiences and Symptoms Screener (STRESS)
timeFrame: Completed as part of the initial evaluation (T0), after drug dose has been determined to be stable and fixed (T1), and after completing the Mindfulness Therapy. (T2) (approximately 20 weeks in total)
measure: Changes in theRetrospective-Modified Overt Aggression Scale (R-MOAS)
timeFrame: Completed as part of the initial evaluation (T0), after drug dose has been determined to be stable and fixed (T1), and after completing the Mindfulness Therapy. (T2)(approximately 20 weeks in total)
measure: Changes in ADHD RS-IV
timeFrame: Completed as part of the initial evaluation (T0), after drug dose has been determined to be stable and fixed (T1), and after completing the Mindfulness Therapy. (T2)(approximately 20 weeks in total)
measure: Changes in the Emotion Reactivity Scale (ERS)
timeFrame: Completed as part of the initial evaluation (T0), after drug dose has been determined to be stable and fixed (T1), and after completing the Mindfulness Therapy. (T2). Also at each medication management appointment(approximately 20 weeks in total)
measure: Youth Self Report (CBCL)
timeFrame: Completed at initial visit only (week 1)
measure: Kaufman Brief Intelligence Test-2
timeFrame: Completed by the adolescent at the initial visit only (week 1)
Secondary outcomes:
measure: Guanfacine Extended Release and Mindfulness Skills Therapy reducing traumatic stress
timeFrame: 20 weeks
measure: Tolerance of Guanfacine Extended Release in subjects between the ages of 12-17 years old.
timeFrame: 20 weeks
measure: Clinical Global Impressions Improvement Scale
timeFrame: Completed ater drug dose has been determined to be stable and fixed (T1) and after completing the Mindfulness Therapy (T2) and each medication management visit.(approximately 20 weeks in total)
measure: Clinical Global Impressions Severity Scale
timeFrame: Completed as part of the initial evaluation (T0), after drug dose has been determined to be stable and fixed (T1), and after completing the Mindfulness Therapy. (T2). Also at each medication management appointment(approximately 20 weeks in total)
measure: Client Credibility Questionnaire (CCQ)
timeFrame: the CCQ will be administered to all youth and parents at the end of session one following presentation of the treatment rationale(approximately 20 weeks in total)
measure: Group Engagement Scale (GES)
timeFrame: At each of the Mindfulness Skills Therapy sessions if the subject is in group therapy.(approximately 10 weeks)
measure: The Screen for Child Anxiety Related Emotional Disorders (SCARED)
timeFrame: Completed as part of the initial evaluation (T0), after drug dose has been determined to be stable and fixed (T1), and after completing the Mindfulness Therapy. (T2). Also at each medication management visit(approximately 20 weeks in total)
measure: Patient Health Questionnaire (PHQ-9)
timeFrame: Completed as part of the initial evaluation (T0), after drug dose has been determined to be stable and fixed (T1), and after completing the Mindfulness Therapy. (T2) Also at each medication management visit(approximately 20 weeks in total)
Other outcomes:
Locations:
city: Farmington
country: United States
facility: UConn Health
state: Connecticut
Study officials:
affiliation: UConn Health
name: Asima F Zehgeer, MD
role: PRINCIPAL_INVESTIGATOR
References: