Attention Deficit Hyperactivity Disorder
Conditions
Keywords
Mothers, ADHD, Treatment, Child
Brief summary
We hypothesize that successfully treating maternal Attention Deficit Hyperactivity Disorder (ADHD) will have a beneficial effect that extends to the child. We believe that multi-component interventions combining maternal stimulant medication, Lisdexamfetamine (LDX), and Behavioral Parent Training (BPT) will improve parenting, maternal, and child outcomes. In terms of improved parenting, we hypothesize that some mothers may respond well to LDX or BPT alone and therefore may not require multi-modal treatment, whereas others may benefit most from multi-modal treatment
Detailed description
The overarching goal of this study is to construct and evaluate an adaptive intervention (i.e., an individualized treatment protocol that is adjusted based on the child-mother dyad's initial response to treatment) to improve the trajectory of ADHD outcomes in at-risk children. Our primary outcome measure for the child will be whether child ADHD symptoms on the Conners Parent and Teacher Rating Scales decreased at the completion of the study. Our secondary outcome measure will be whether there was a need for medication for the child over the course of the study. The primary outcome for the mother will be the Conners Adult ADHD Rating Scale (CAARS) Attention Scale and the Clinical Global Impression-Severity scale (CGI-S).
Interventions
DRUGVyvanse (lisdexamphetamine)
Active ADHD drug, Vyvanse, is administered to mother.
BEHAVIORALBehavior Parent Training
Mother is given 8 weeks of individual sessions of behavioral parent training
Sponsors
Shire
Seattle Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Mothers Inclusion Criteria: * Sign informed consent * Be between 21-50 years old (inclusive) at the screening visit and English-speaking * At screening (after washout, if required) meet full Diagnostic and Statistical Manual (DSM-IV) criteria for ADHD, any subtype * Have current CGI-S-ADHD rating \> 4 and \< 8 * Have findings on physical exam (PE), laboratory studies, vital signs, and electrocardiogram (ECG) judged to be normal for age with no contraindications for methylphenidate (MPH) treatment * Have pulse and blood pressure (BP) within 95% of age and gender mean * Commit to the entire visit schedule for the study * Be able to complete all study assessments * Women of childbearing potential (not surgically sterile or post-menopausal) must agree to use a medically-accepted contraception method consistently * Mothers with comorbid mood/anxiety disorders which are effectively treated with Selective Serotonin Reuptake Inhibitors (SSRIs) will be eligible for participation, provided this medication has not changed within 30 days, is well tolerated, and that current mood symptoms are not severe or associated with active suicidal ideation. Also, the prescribing physician must approve of their participation in the study. Mothers
Exclusion criteria
* History of allergic reactions or severe negative response to study medications * History of alcohol/substance abuse in the past 3 months or a positive urinary toxic screen on initial evaluation that is not explained by a time-limited medical circumstance * History of or current bipolar illness, schizophrenia, psychoses, or significant suicidal risk * History of chronic or acute medical disorder for which stimulant therapy would be contraindicated (e.g., glaucoma, hypertension) Child Inclusion Criteria: * Sign assent if older than 6 * Be between the ages of 4-8 * symptoms of ADHD (Conners Hyperactivity Index \> 60), no prior treatment with effective doses of stimulants, defined as one or more weeks of treatment with adequate doses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Child Behavioral Functioning | Baseline, Weeks 8 and 16 | Child symptom severity will be assessed using the Clinical Global Impression - Severity (CGI-s) scale. This was collected at Baseline, Week 8 (end of Phase 1) and Week 16 (end of Phase 2). The CGI-S scale summarizes the clinician's impression of the participant's symptom improvement and ranges from 1-7 with 1 representing very much improved and 7 representing very much worse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maternal Behavioral Functioning | Baseline, Weeks 8 and 16 | The Clinical Global Impression - Severity (CGI-S) scale will be used. This was collected at Baseline, Week 8 (end of Phase 1) and Week 16 (end of Phase 2). The CGI-S scale summarizes the clinician's impression of the participant's symptom improvement and ranges from 1-7 with 1 representing very much improved and 7 representing very much worse. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Parental and Family Functioning | Baseline, Weeks 8 and 16 | The Dyadic Parent-Child Interaction Coding System (DPICS) will be used at baseline, week 8, and week 16 to provide an observational measure of positive and negative behaviors of the mother toward the child. Instances of positive (e.g. praise) and negative (e.g. criticism) behaviors are coded by study raters trained to reliability; scores range from 0 to no upper limit. Higher numbers indicate higher instances of the observed behaviors. |
Countries
United States
Participant flow
Recruitment details
Eligible participants were recruited from the investigators' practices, clinic referrals, online advertisements, and radio advertisements. Participants were enrolled between September 2012 and December 2016.
Pre-assignment details
7 participants didn't meet inclusion criteria, 1 decided not to participate after screening, 2 withdrew due to time commitment issues, 1 had a comorbid psychiatric disorder, 1 had a physical contraindication.
Participants by arm
| Arm | Count |
|---|---|
| Maternal Medication Then Meds The mothers in this treatment arm are given an active medication to treat ADHD (Vyvanse) in the first phase of the study, and in the second phase are randomized to enhanced medication
Vyvanse (lisdexamphetamine): Active ADHD drug, Vyvanse, is administered to mother. | 22 |
| BPT Then Continued Beh tx The mothers in this treatment arm are given Behavior Parent Training in the first phase of the study, and in the second phase are randomized to enhanced behavioral treatment.
Behavior Parent Training: Mother is given 8 weeks of individual sessions of behavioral parent training | 18 |
| Maternal Medication Then BPT The mothers in this treatment arm are given an active medication to treat ADHD (Vyvanse) in the first phase of the study, and in the second phase are randomized to combined treatment (adding Behavior Parent Training).
Vyvanse (lisdexamphetamine): Active ADHD drug, Vyvanse, is administered to mother.
Behavior Parent Training: Mother is given 8 weeks of individual sessions of behavioral parent training | 22 |
| BPT Then Maternal Medication The mothers in this treatment arm are given Behavior Parent Training in the first phase of the study, and in the second phase are randomized to active ADHD medication, Vyvanse.
Vyvanse (lisdexamphetamine): Active ADHD drug, Vyvanse, is administered to mother.
Behavior Parent Training: Mother is given 8 weeks of individual sessions of behavioral parent training | 20 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Phase 1 | Time commitment issues | 0 | 0 | 1 | 0 |
| Phase 2 | Physician Decision | 0 | 0 | 0 | 1 |
| Phase 2 | Time commitment Issues | 0 | 2 | 0 | 0 |
| Phase 2 | Unsatisfied with Randomization assignmen | 1 | 0 | 0 | 0 |
| Phase 2 | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Maternal Medication Then Meds | BPT Then Continued Beh tx | Maternal Medication Then BPT | BPT Then Maternal Medication |
|---|---|---|---|---|---|
| Age, Continuous Child age | 6.17 years STANDARD_DEVIATION 1.41 | 6.00 years STANDARD_DEVIATION 1.73 | 5.89 years STANDARD_DEVIATION 1.05 | 6.18 years STANDARD_DEVIATION 1.47 | 6.60 years STANDARD_DEVIATION 1.35 |
| Age, Continuous Mom age | 39.59 years STANDARD_DEVIATION 6.38 | 40.55 years STANDARD_DEVIATION 7.31 | 39.00 years STANDARD_DEVIATION 5.94 | 37.82 years STANDARD_DEVIATION 5.78 | 41.00 years STANDARD_DEVIATION 6.73 |
| Ethnicity (NIH/OMB) Child Hispanic or Latino | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Child Not Hispanic or Latino | 32 Participants | 9 Participants | 8 Participants | 7 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Child Unknown or Not Reported | 6 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Mom Hispanic or Latino | 4 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Mom Not Hispanic or Latino | 37 Participants | 9 Participants | 9 Participants | 10 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Mom Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Child Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Child Race Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Child Race Black or African American | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Child Race More than one race | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Child Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Child Race Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Child Race White | 35 Participants | 9 Participants | 9 Participants | 9 Participants | 8 Participants |
| Race (NIH/OMB) Mother Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Mother Race Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Mother Race Black or African American | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Mother Race More than one race | 4 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Mother Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Mother Race Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Mother Race White | 34 Participants | 9 Participants | 9 Participants | 9 Participants | 7 Participants |
| Sex/Gender, Customized Child gender Female | 18 Participants | 5 Participants | 3 Participants | 5 Participants | 5 Participants |
| Sex/Gender, Customized Child gender Male | 23 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants |
| Sex/Gender, Customized Parent gender Female | 41 Participants | 11 Participants | 9 Participants | 11 Participants | 10 Participants |
| Sex/Gender, Customized Parent gender Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 27 | 12 / 22 | 12 / 19 | 5 / 12 | 4 / 6 | 1 / 2 |
| serious Total, serious adverse events | 0 / 27 | 0 / 22 | 0 / 19 | 0 / 12 | 0 / 6 | 0 / 2 |
Outcome results
Primary
Child Behavioral Functioning
Child symptom severity will be assessed using the Clinical Global Impression - Severity (CGI-s) scale. This was collected at Baseline, Week 8 (end of Phase 1) and Week 16 (end of Phase 2). The CGI-S scale summarizes the clinician's impression of the participant's symptom improvement and ranges from 1-7 with 1 representing very much improved and 7 representing very much worse.
Time frame: Baseline, Weeks 8 and 16
Population: 7 participants had missing data, the Child CGI-S was not collected at any of the study visits for these participants because they completed the study before this measure was added to the protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maternal Medication Then Additional Maternal Medication | Child Behavioral Functioning | Baseline | 4.78 units on a scale | Standard Deviation 0.92 |
| Maternal Medication Then Additional Maternal Medication | Child Behavioral Functioning | Week 16 | 4.13 units on a scale | Standard Deviation 0.93 |
| Maternal Medication Then Additional Maternal Medication | Child Behavioral Functioning | Week 8 | 4.33 units on a scale | Standard Deviation 0.67 |
| Maternal Behavioral Parent Training (BPT) Then Additional BPT | Child Behavioral Functioning | Baseline | 4.56 units on a scale | Standard Deviation 1.42 |
| Maternal Behavioral Parent Training (BPT) Then Additional BPT | Child Behavioral Functioning | Week 16 | 3.67 units on a scale | Standard Deviation 1.25 |
| Maternal Behavioral Parent Training (BPT) Then Additional BPT | Child Behavioral Functioning | Week 8 | 3.75 units on a scale | Standard Deviation 1.09 |
| Maternal Medication Then BPT | Child Behavioral Functioning | Week 8 | 3.63 units on a scale | Standard Deviation 0.99 |
| Maternal Medication Then BPT | Child Behavioral Functioning | Baseline | 4.44 units on a scale | Standard Deviation 0.96 |
| Maternal Medication Then BPT | Child Behavioral Functioning | Week 16 | 3.38 units on a scale | Standard Deviation 1.22 |
| BPT Then Maternal Medication | Child Behavioral Functioning | Baseline | 4.67 units on a scale | Standard Deviation 1.33 |
| BPT Then Maternal Medication | Child Behavioral Functioning | Week 16 | 3.22 units on a scale | Standard Deviation 0.92 |
| BPT Then Maternal Medication | Child Behavioral Functioning | Week 8 | 3.78 units on a scale | Standard Deviation 0.63 |
Secondary
Maternal Behavioral Functioning
The Clinical Global Impression - Severity (CGI-S) scale will be used. This was collected at Baseline, Week 8 (end of Phase 1) and Week 16 (end of Phase 2). The CGI-S scale summarizes the clinician's impression of the participant's symptom improvement and ranges from 1-7 with 1 representing very much improved and 7 representing very much worse.
Time frame: Baseline, Weeks 8 and 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maternal Medication Then Additional Maternal Medication | Maternal Behavioral Functioning | Baseline | 4.64 units on a scale | Standard Deviation 0.64 |
| Maternal Medication Then Additional Maternal Medication | Maternal Behavioral Functioning | Week 16 | 3.20 units on a scale | Standard Deviation 0.6 |
| Maternal Medication Then Additional Maternal Medication | Maternal Behavioral Functioning | Week 8 | 3.55 units on a scale | Standard Deviation 0.5 |
| Maternal Behavioral Parent Training (BPT) Then Additional BPT | Maternal Behavioral Functioning | Baseline | 4.50 units on a scale | Standard Deviation 0.5 |
| Maternal Behavioral Parent Training (BPT) Then Additional BPT | Maternal Behavioral Functioning | Week 16 | 3.86 units on a scale | Standard Deviation 0.35 |
| Maternal Behavioral Parent Training (BPT) Then Additional BPT | Maternal Behavioral Functioning | Week 8 | 3.67 units on a scale | Standard Deviation 0.67 |
| Maternal Medication Then BPT | Maternal Behavioral Functioning | Week 8 | 2.60 units on a scale | Standard Deviation 0.66 |
| Maternal Medication Then BPT | Maternal Behavioral Functioning | Baseline | 4.82 units on a scale | Standard Deviation 0.72 |
| Maternal Medication Then BPT | Maternal Behavioral Functioning | Week 16 | 2.60 units on a scale | Standard Deviation 1.02 |
| BPT Then Maternal Medication | Maternal Behavioral Functioning | Baseline | 4.45 units on a scale | Standard Deviation 0.5 |
| BPT Then Maternal Medication | Maternal Behavioral Functioning | Week 16 | 2.56 units on a scale | Standard Deviation 0.96 |
| BPT Then Maternal Medication | Maternal Behavioral Functioning | Week 8 | 3.80 units on a scale | Standard Deviation 0.87 |
Other Pre-specified
Parental and Family Functioning
The Dyadic Parent-Child Interaction Coding System (DPICS) will be used at baseline, week 8, and week 16 to provide an observational measure of positive and negative behaviors of the mother toward the child. Instances of positive (e.g. praise) and negative (e.g. criticism) behaviors are coded by study raters trained to reliability; scores range from 0 to no upper limit. Higher numbers indicate higher instances of the observed behaviors.
Time frame: Baseline, Weeks 8 and 16
Population: 6 participants were in the study before this assessment was added. 2 participants did not complete this assessment before they withdrew from the study. 3 participants withdrew from the study after the baseline visit (1 in the medication then medication arm after week 8, 1 in the Medication then BPT arm and 1 in BPT then BPT arm).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maternal Medication Then Additional Maternal Medication | Parental and Family Functioning | Total Positive Parenting | 23.61 instances observed | Standard Deviation 13.7 |
| Maternal Medication Then Additional Maternal Medication | Parental and Family Functioning | Total Negative Parenting | 11.33 instances observed | Standard Deviation 11.36 |
| Maternal Behavioral Parent Training (BPT) Then Additional BPT | Parental and Family Functioning | Total Positive Parenting | 27.17 instances observed | Standard Deviation 12.39 |
| Maternal Behavioral Parent Training (BPT) Then Additional BPT | Parental and Family Functioning | Total Negative Parenting | 17.01 instances observed | Standard Deviation 12.79 |
| Maternal Medication Then BPT | Parental and Family Functioning | Total Positive Parenting | 32.56 instances observed | Standard Deviation 16.75 |
| Maternal Medication Then BPT | Parental and Family Functioning | Total Negative Parenting | 10.51 instances observed | Standard Deviation 10.8 |
| BPT Then Maternal Medication | Parental and Family Functioning | Total Positive Parenting | 41.67 instances observed | Standard Deviation 26.03 |
| BPT Then Maternal Medication | Parental and Family Functioning | Total Negative Parenting | 8.64 instances observed | Standard Deviation 5.19 |
| Maternal Medication Then Behavior Parent Training - Week 8 | Parental and Family Functioning | Total Negative Parenting | 13.47 instances observed | Standard Deviation 14.58 |
| Maternal Medication Then Behavior Parent Training - Week 8 | Parental and Family Functioning | Total Positive Parenting | 31.55 instances observed | Standard Deviation 19.73 |
| Maternal Medication Then Behavior Parent Training - Week 16 | Parental and Family Functioning | Total Positive Parenting | 51.70 instances observed | Standard Deviation 25.04 |
| Maternal Medication Then Behavior Parent Training - Week 16 | Parental and Family Functioning | Total Negative Parenting | 5.96 instances observed | Standard Deviation 5.32 |
| Behavior Parent Training Then Maternal Medication - Baseline | Parental and Family Functioning | Total Negative Parenting | 8.04 instances observed | Standard Deviation 6.77 |
| Behavior Parent Training Then Maternal Medication - Baseline | Parental and Family Functioning | Total Positive Parenting | 21.83 instances observed | Standard Deviation 13.93 |
| Behavior Parent Training Then Maternal Medication - Week 8 | Parental and Family Functioning | Total Positive Parenting | 46.33 instances observed | Standard Deviation 28.65 |
| Behavior Parent Training Then Maternal Medication - Week 8 | Parental and Family Functioning | Total Negative Parenting | 5.01 instances observed | Standard Deviation 4.74 |
| Behavior Parent Training Then Maternal Medication - Week 16 | Parental and Family Functioning | Total Positive Parenting | 44.07 instances observed | Standard Deviation 46.78 |
| Behavior Parent Training Then Maternal Medication - Week 16 | Parental and Family Functioning | Total Negative Parenting | 7.66 instances observed | Standard Deviation 6.64 |
| Behavior Parent Training Then Additional BPT - Baseline | Parental and Family Functioning | Total Positive Parenting | 17.49 instances observed | Standard Deviation 10.48 |
| Behavior Parent Training Then Additional BPT - Baseline | Parental and Family Functioning | Total Negative Parenting | 10.64 instances observed | Standard Deviation 6.28 |
| Behavior Parent Training Then Additional BPT - Week 8 | Parental and Family Functioning | Total Negative Parenting | 9.44 instances observed | Standard Deviation 4.48 |
| Behavior Parent Training Then Additional BPT - Week 8 | Parental and Family Functioning | Total Positive Parenting | 34.71 instances observed | Standard Deviation 14.65 |
| Behavior Parent Training Then Additional BPT - Week 16 | Parental and Family Functioning | Total Negative Parenting | 8.85 instances observed | Standard Deviation 4.34 |
| Behavior Parent Training Then Additional BPT - Week 16 | Parental and Family Functioning | Total Positive Parenting | 39.52 instances observed | Standard Deviation 20.06 |