Attention Deficit Hyperactivity Disorder (ADHD)
Conditions
Keywords
cardiovascular testing, home blood pressure monitoring, office home blood pressure monitoring, cardiopulmonary exercise testing, transthoracic echocardiography, Lisdexamfetamine, Vyvanse, normotensive and hypertensive adults with ADHD, ADHD medication.
Brief summary
The purpose of this research study is to learn about the effects of a medication called Vyvanse on the heart (cardiovascular system). The U.S. Food and Drug Administration (FDA) has approved Vyvanse for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). People who have ADHD have trouble paying attention, organizing, and planning; these symptoms can cause problems at work, socially and at home. Vyvanse (also known as Lisdexamfetamine) is a stimulant class medication. There have been reports of serious cardiovascular effects in children and adults treated with stimulants. While there is no definite evidence that these events were related to the use of stimulants, the deaths have raised questions about the cardiovascular safety of stimulants. The study will involve in-depth cardiovascular tests, namely echocardiograph (ultrasound of the heart) and cardiopulmonary exercise test (also called stress test; subjects exercise on a bicycle while measuring their heart activity and breathing is monitored by cardiologists). The investigators predict to see changes in blood pressure and heart rate as shown in previous clinical studies, and that the in-depth cardiovascular tests will provide new insights into the cardiovascular impact of stimulants.
Interventions
DRUGLisdexamfetamine
Lisdexamfetamine daily until the completion of participation in the clinical trial (up to Week 11 or final study visit). Subjects will start on 30 mg of LDX per day for the first week of treatment. The dose will be increased weekly in 20 mg increments, up to a 70 mg daily (maximum). If significant adverse effects (AE) occur, the daily dose may be reduced by 20 mg. At subsequent visits, a higher dose may be resumed if tolerated. Both cohorts of the study will follow the same treatment plan.
Sponsors
Shire
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female outpatients 18-60 years of age. 2. A current DSM-IV-TR diagnosis of ADHD, confirmed by the Adult ADHD Clinical Diagnostic Scale (ACDS) at Screening. 3. In phase two only; Stage I primary hypertension (SBP 140-159 mm Hg/DBP 90-99 mm Hg) as defined by Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (Chobanian et al, 2003). 4. In phase two only; Treatment with stable doses of up to two FDA approved antihypertensive medications achieving a stable blood pressure of \<135/85. Acceptable classes of medications include diuretics, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors or receptor blockers, aldosterone antagonists, calcium-channel blockers (Rosendorff et al, 2007).
Exclusion criteria
1. Pregnant or nursing females. 2. Clinically significant cardiovascular history, including angina, syncope, thrombosis, aneurysm, myocardial infarction, myocarditis, valvular disease, heart failure, or arrhythmia. Hypertension is exclusionary in phase one subjects. 3. In phase two; hypertension is not exclusionary, however blood pressure with antihypertensive treatment of ≥135/85 at baseline is exclusionary. 4. Clinically significant or unstable medical condition including pulmonary (asthma, edema, thrombosis), renal, hepatic, metabolic (thyroid) or neurological disorder, based upon a medical history. 5. Orthopedic impairment or BMI that significantly impacts or restricts exercise performance testing, per clinician judgment. 6. Any clinically unstable psychiatric conditions including suicidality, homicidality, bipolar disorder, psychosis. 7. Current (within 3 months) DSM-IV-TR criteria for current abuse or dependence with any psychoactive substance other than nicotine, including alcohol, prescription medicines and/or street drugs. In addition, subjects with clinically significant histories of dependence on alcohol, prescription medications or street drugs will be excluded, if such history places subjects at heightened risk, and/or may be associated with cardiovascular sequelae, based on clinician judgment. 8. Ongoing treatment with any psychotropic medication, including anxiolytics, antidepressants, mood stabilizers. 9. Use of Monoamine Oxidase Inhibitors (MAOIs) including linezolid within two weeks prior to starting study medication. 10. Mental retardation (IQ \< 75). 11. History of intolerance or allergy to LDX. 12. Diagnosis of glaucoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricle Size | 3-6 months | Size of the heart's left ventricle chamber (Left Ventricular End Diastolic Dimension; LVEDD) following 3-6 months of stimulant medication, according to cardiac ultrasound (transthoracic echocardiogram; TTE) |
| Cardiac Function Index (E/A Ratio) | 3-6 months | Left ventricle diastolic function index, following 3-6 months of stimulant medication, according to cardiac ultrasound (transthoracic echocardiogram; TTE) |
| Blood Pressure at Maximum Exertion | 3-6 months | Diastolic blood pressure (DBP) at maximum exertion following 3-6 months of stimulant medication, according to cardiopulmonary exercise testing (CPET) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normotensive Adults With ADHD Group 1 is comprised of adults who meet DSM-IV-TR criteria for ADHD and do not have high blood pressure. | 15 |
| Primary Hypertensive Adults With ADHD Group 2 is comprised of adults who meet the full DSM-IV criteria for ADHD, and who also high blood pressure being treated with stable doses of up to two FDA approved hypertensive medications to achieve a stable blood pressure of \<135/85. High blood pressure is defined as 140-159mmHg/90-99 mmHg. | 9 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Confounded endpoint data | 1 | 0 |
| Overall Study | Ineligible, abnormal cardiac histo | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Primary Hypertensive Adults With ADHD | Normotensive Adults With ADHD | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 15 Participants | 24 Participants |
| Age Continuous | 51.33 years STANDARD_DEVIATION 7.87 | 34.80 years STANDARD_DEVIATION 11.59 | 41.00 years STANDARD_DEVIATION 13.05 |
| Region of Enrollment United States | 9 participants | 15 participants | 24 participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 11 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 14 | 8 / 8 |
| serious Total, serious adverse events | 0 / 14 | 0 / 8 |
Outcome results
Primary
Blood Pressure at Maximum Exertion
Diastolic blood pressure (DBP) at maximum exertion following 3-6 months of stimulant medication, according to cardiopulmonary exercise testing (CPET)
Time frame: 3-6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normotensive Adults With ADHD | Blood Pressure at Maximum Exertion | 80.43 mmHg | Standard Deviation 11.97 |
| Primary Hypertensive Adults With ADHD | Blood Pressure at Maximum Exertion | 85.00 mmHg | Standard Deviation 8.07 |
Primary
Cardiac Function Index (E/A Ratio)
Left ventricle diastolic function index, following 3-6 months of stimulant medication, according to cardiac ultrasound (transthoracic echocardiogram; TTE)
Time frame: 3-6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normotensive Adults With ADHD | Cardiac Function Index (E/A Ratio) | 1.38 cm/sec/cm/sec | Standard Deviation 0.48 |
| Primary Hypertensive Adults With ADHD | Cardiac Function Index (E/A Ratio) | 1.36 cm/sec/cm/sec | Standard Deviation 0.84 |
Primary
Left Ventricle Size
Size of the heart's left ventricle chamber (Left Ventricular End Diastolic Dimension; LVEDD) following 3-6 months of stimulant medication, according to cardiac ultrasound (transthoracic echocardiogram; TTE)
Time frame: 3-6 months
Population: 14 subjects completed endpoint TTE; one HTN subject missed the scheduled endpoint TTE appointment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normotensive Adults With ADHD | Left Ventricle Size | 44.42 mm | Standard Deviation 7.07 |
| Primary Hypertensive Adults With ADHD | Left Ventricle Size | 43.57 mm | Standard Deviation 6.13 |