Cardiovascular Study of Lisdexamfetamine in Healthy and Hypertensive Attention Deficit Hyperactivity Disorder Adults

An In Depth Cardiovascular Study of Lisdexamfetamine (LDX; Vyvanse) in Healthy and Treated Hypertensive Adults With Attention Deficit Hyperactivity Disorder (ADHD)

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.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
• Intervention / Treatment: Drug: Lisdexamfetamine

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02138
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lisdexamfetamine; Adults who meet DSM-IV-TR criteria for ADHD. Group 1 is normotensive adults; Group 1 does not have high blood pressure. Group 2 is primary hypertensive adults; Group 2 does have high blood pressure and is being treated with stable doses of hypertensive medications achieving a blood pressure of <135/85.

Drug: Lisdexamfetamine; 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.; Other Names: Vyvanse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	3-6 months
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)	3-6 months
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)	3-6 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Shire

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: September 12, 2008
• First Submitted That Met QC Criteria: September 15, 2008
• First Posted (Estimate): September 16, 2008

Study Record Updates

• Last Update Posted (Estimate): September 24, 2012
• Last Update Submitted That Met QC Criteria: August 22, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: transthoracic echocardiography; cardiopulmonary exercise testing; home blood pressure monitoring; Vyvanse; Lisdexamfetamine; cardiovascular testing; office home blood pressure monitoring; normotensive and hypertensive adults with ADHD; ADHD medication.
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: 2008-P-000121