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

Attention Deficit Hyperactivity Disorder (ADHD) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00753012
• Other study ID #: 2008-P-000121
• Status: Completed
• Phase: Phase 4
• First received: September 12, 2008
• Last updated: August 22, 2012
• Start date: April 2008
• Est. completion date: March 2011

Study information

• Verified date: August 2012
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder (ADHD)
• Hyperkinesis

Intervention

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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Cambridge	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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)	3-6 months	Yes
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)	3-6 months	Yes
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)	3-6 months	Yes