Cardiovascular Study of Lisdexamfetamine in Healthy and Hypertensive Attention Deficit Hyperactivity Disorder Adults
Condition: Attention Deficit Hyperactivity Disorder (ADHD)
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: Lisdexamfetamine
Intervention description: 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.
Intervention MeSH terms: Lisdexamfetamine Dimesylate
Phase: Phase 4
Study type: Interventional
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
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.

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.
    

Eligibility criteria:

        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